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Cryptocurrency News: XRP Validators, Malta, and Practical Tokens

Cryptocurrency News & Market Summary
Investors finally saw some light at the end of the tunnel last week, with cryptos soaring across the board. No one quite knows what kicked off the rally—as it could have been any of the stories we discuss below—but the net result was positive.

Of course, prices won’t stay on this rocket ride forever. I expect to see a resurgence of volatility in short order, because the market is moving as a single unit. Everything is rising in tandem.

This tells me that investors are simply “buying the dip” rather than identifying which cryptos have enough real-world value to outlive the crash.

So if you want to know when.

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Cryptocurrency News: XRP Validators, Malta, and Practical Tokens

Cryptocurrency News: Bitcoin ETFs, Andreessen Horowitz, and Contradictions in Crypto

Cryptocurrency News
This was a bloody week for cryptocurrencies. Everything was covered in red, from Ethereum (ETH) on down to the Basic Attention Token (BAT).

Some investors claim it was inevitable. Others say that price manipulation is to blame.

We think the answers are more complicated than either side has to offer, because our research reveals deep contradictions between the price of cryptos and the underlying development of blockchain projects.

For instance, a leading venture capital (VC) firm launched a $300.0-million crypto investment fund, yet liquidity continues to dry up in crypto markets.

Another example is the U.S. Securities and Exchange Commission’s.

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Cryptocurrency News: Bitcoin ETFs, Andreessen Horowitz, and Contradictions in Crypto

Cryptocurrency News: Looking Past the Bithumb Crypto Hack

Another Crypto Hack Derails Recovery
Since our last report, hackers broke into yet another cryptocurrency exchange. This time the target was Bithumb, a Korean exchange known for high-flying prices and ultra-active traders.

While the hackers made off with approximately $31.5 million in funds, the exchange is working with relevant authorities to return the stolen tokens to their respective owners. In the event that some is still missing, the exchange will cover the losses. (Source: “Bithumb Working With Other Crypto Exchanges to Recover Hacked Funds,”.

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Cryptocurrency News: Looking Past the Bithumb Crypto Hack

Cryptocurrency News: This Week on Bitfinex, Tether, Coinbase, & More

Cryptocurrency News
On the whole, cryptocurrency prices are down from our previous report on cryptos, with the market slipping on news of an exchange being hacked and a report about Bitcoin manipulation.

However, there have been two bright spots: 1) an official from the U.S. Securities and Exchange Commission (SEC) said that Ethereum is not a security, and 2) Coinbase is expanding its selection of tokens.

Let’s start with the good news.
SEC Says ETH Is Not a Security
Investors have some reason to cheer this week. A high-ranking SEC official told attendees of the Yahoo! All Markets Summit: Crypto that Ethereum and Bitcoin are not.

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Cryptocurrency News: This Week on Bitfinex, Tether, Coinbase, & More

Ripple Price Forecast: XRP vs SWIFT, SEC Updates, and More

Ripple vs SWIFT: The War Begins
While most criticisms of XRP do nothing to curb my bullish Ripple price forecast, there is one obstacle that nags at my conscience. Its name is SWIFT.

The Society for Worldwide Interbank Financial Telecommunication (SWIFT) is the king of international payments.

It coordinates wire transfers across 11,000 banks in more than 200 countries and territories, meaning that in order for XRP prices to ascend to $10.00, Ripple needs to launch a successful coup. That is, and always has been, an unwritten part of Ripple’s story.

We’ve seen a lot of progress on that score. In the last three years, Ripple wooed more than 100 financial firms onto its.

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Ripple Price Forecast: XRP vs SWIFT, SEC Updates, and More

Cryptocurrency Price Forecast: Trust Is Growing, But Prices Are Falling

Trust Is Growing…
Before we get to this week’s cryptocurrency news, analysis, and our cryptocurrency price forecast, I want to share an experience from this past week. I was at home watching the NBA playoffs, trying to ignore the commercials, when a strange advertisement caught my eye.

It followed a tomato from its birth on the vine to its end on the dinner table (where it was served as a bolognese sauce), and a diamond from its dusty beginnings to when it sparkled atop an engagement ring.

The voiceover said: “This is a shipment passed 200 times, transparently tracked from port to port. This is the IBM blockchain.”

Let that sink in—IBM.

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Cryptocurrency Price Forecast: Trust Is Growing, But Prices Are Falling

Cryptocurrency News: Vitalik Buterin Doesn’t Care About Bitcoin ETFs

Cryptocurrency News
While headline numbers look devastating this week, investors might take some solace in knowing that cryptocurrencies found their bottom at roughly $189.8 billion in market cap—that was the low point. Since then, investors put more than $20.0 billion back into the market.

During the rout, Ethereum broke below $300.00 and XRP fell below $0.30, marking yearly lows for both tokens. The same was true down the list of the top 100 biggest cryptos.

Altcoins took the brunt of the hit. BTC Dominance, which reveals how tightly investment is concentrated in Bitcoin, rose from 42.62% to 53.27% in just one month, showing that investors either fled altcoins at higher.

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Cryptocurrency News: Vitalik Buterin Doesn’t Care About Bitcoin ETFs

Cryptocurrency News: New Exchanges Could Boost Crypto Liquidity

Cryptocurrency News
Even though the cryptocurrency news was upbeat in recent days, the market tumbled after the U.S. Securities and Exchange Commission (SEC) rejected calls for a Bitcoin (BTC) exchange-traded fund (ETF).

That news came as a blow to investors, many of whom believe the ETF would open the cryptocurrency industry up to pension funds and other institutional investors. This would create a massive tailwind for cryptos, they say.

So it only follows that a rejection of the Bitcoin ETF should send cryptos tumbling, correct? Well, maybe you can follow that logic. To me, it seems like a dramatic overreaction.

I understand that legitimizing cryptos is important. But.

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Cryptocurrency News: New Exchanges Could Boost Crypto Liquidity

Cryptocurrency News: Bitcoin ETF Rejection, AMD Microchip Sales, and Hedge Funds

Cryptocurrency News
Although cryptocurrency prices were heating up last week (Bitcoin, especially), regulators poured cold water on the rally by rejecting calls for a Bitcoin exchange-traded fund (ETF). This is the second time that the proposal fell on deaf ears. (More on that below.)

Crypto mining ran into similar trouble, as you can see from Advanced Micro Devices, Inc.‘s (NASDAQ:AMD) most recent quarterly earnings. However, it wasn’t all bad news. Investors should, for instance, be cheering the fact that hedge funds are ramping up their involvement in cryptocurrency markets.

Without further ado, here are those stories in greater detail.
ETF Rejection.

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Cryptocurrency News: Bitcoin ETF Rejection, AMD Microchip Sales, and Hedge Funds

Cryptocurrency News: What You Need to Know This Week

Cryptocurrency News
Cryptocurrencies traded sideways since our last report on cryptos. However, I noticed something interesting when playing around with Yahoo! Finance’s cryptocurrency screener: There are profitable pockets in this market.

Incidentally, Yahoo’s screener is far superior to the one on CoinMarketCap, so if you’re looking to compare digital assets, I highly recommend it.

But let’s get back to my epiphany.

In the last month, at one point or another, most crypto assets on our favorites list saw double-digit increases. It’s true that each upswing was followed by a hard crash, but investors who rode the trend would have made a.

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Cryptocurrency News: What You Need to Know This Week

Basic Genetics

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Basic Genetics

Human genetics | biology | Britannica.com

Human genetics, study of the inheritance of characteristics by children from parents. Inheritance in humans does not differ in any fundamental way from that in other organisms.

The study of human heredity occupies a central position in genetics. Much of this interest stems from a basic desire to know who humans are and why they are as they are. At a more practical level, an understanding of human heredity is of critical importance in the prediction, diagnosis, and treatment of diseases that have a genetic component. The quest to determine the genetic basis of human health has given rise to the field of medical genetics. In general, medicine has given focus and purpose to human genetics, so the terms medical genetics and human genetics are often considered synonymous.

Read More on This Topic

genetics: Human genetics

Some geneticists specialize in the hereditary processes of human genetics. Most of the emphasis is on understanding and treating genetic disease and genetically influenced ill health, areas collectively known as medical genetics. One broad area of activity is laboratory research dealing with the

A new era in cytogenetics, the field of investigation concerned with studies of the chromosomes, began in 1956 with the discovery by Jo Hin Tjio and Albert Levan that human somatic cells contain 23 pairs of chromosomes. Since that time the field has advanced with amazing rapidity and has demonstrated that human chromosome aberrations rank as major causes of fetal death and of tragic human diseases, many of which are accompanied by mental retardation. Since the chromosomes can be delineated only during mitosis, it is necessary to examine material in which there are many dividing cells. This can usually be accomplished by culturing cells from the blood or skin, since only the bone marrow cells (not readily sampled except during serious bone marrow disease such as leukemia) have sufficient mitoses in the absence of artificial culture. After growth, the cells are fixed on slides and then stained with a variety of DNA-specific stains that permit the delineation and identification of the chromosomes. The Denver system of chromosome classification, established in 1959, identified the chromosomes by their length and the position of the centromeres. Since then the method has been improved by the use of special staining techniques that impart unique light and dark bands to each chromosome. These bands permit the identification of chromosomal regions that are duplicated, missing, or transposed to other chromosomes.

Micrographs showing the karyotypes (i.e., the physical appearance of the chromosome) of a male and a female have been produced. In a typical micrograph the 46 human chromosomes (the diploid number) are arranged in homologous pairs, each consisting of one maternally derived and one paternally derived member. The chromosomes are all numbered except for the X and the Y chromosomes, which are the sex chromosomes. In humans, as in all mammals, the normal female has two X chromosomes and the normal male has one X chromosome and one Y chromosome. The female is thus the homogametic sex, as all her gametes normally have one X chromosome. The male is heterogametic, as he produces two types of gametesone type containing an X chromosome and the other containing a Y chromosome. There is good evidence that the Y chromosome in humans, unlike that in Drosophila, is necessary (but not sufficient) for maleness.

A human individual arises through the union of two cells, an egg from the mother and a sperm from the father. Human egg cells are barely visible to the naked eye. They are shed, usually one at a time, from the ovary into the oviducts (fallopian tubes), through which they pass into the uterus. Fertilization, the penetration of an egg by a sperm, occurs in the oviducts. This is the main event of sexual reproduction and determines the genetic constitution of the new individual.

Human sex determination is a genetic process that depends basically on the presence of the Y chromosome in the fertilized egg. This chromosome stimulates a change in the undifferentiated gonad into that of the male (a testicle). The gonadal action of the Y chromosome is mediated by a gene located near the centromere; this gene codes for the production of a cell surface molecule called the H-Y antigen. Further development of the anatomic structures, both internal and external, that are associated with maleness is controlled by hormones produced by the testicle. The sex of an individual can be thought of in three different contexts: chromosomal sex, gonadal sex, and anatomic sex. Discrepancies between these, especially the latter two, result in the development of individuals with ambiguous sex, often called hermaphrodites. The phenomenon of homosexuality is of uncertain cause and is unrelated to the above sex-determining factors. It is of interest that in the absence of a male gonad (testicle) the internal and external sex anatomy is always female, even in the absence of a female ovary. A female without ovaries will, of course, be infertile and will not experience any of the female developmental changes normally associated with puberty. Such a female will often have Turners syndrome.

If X-containing and Y-containing sperm are produced in equal numbers, then according to simple chance one would expect the sex ratio at conception (fertilization) to be half boys and half girls, or 1 : 1. Direct observation of sex ratios among newly fertilized human eggs is not yet feasible, and sex-ratio data are usually collected at the time of birth. In almost all human populations of newborns, there is a slight excess of males; about 106 boys are born for every100 girls. Throughout life, however, there is a slightly greater mortality of males; this slowly alters the sex ratio until, beyond the age of about 50 years, there is an excess of females. Studies indicate that male embryos suffer a relatively greater degree of prenatal mortality, so the sex ratio at conception might be expected to favour males even more than the 106 : 100 ratio observed at birth would suggest. Firm explanations for the apparent excess of male conceptions have not been established; it is possible that Y-containing sperm survive better within the female reproductive tract, or they may be a little more successful in reaching the egg in order to fertilize it. In any case, the sex differences are small, the statistical expectation for a boy (or girl) at any single birth still being close to one out of two.

During gestationthe period of nine months between fertilization and the birth of the infanta remarkable series of developmental changes occur. Through the process of mitosis, the total number of cells changes from 1 (the fertilized egg) to about 2 1011. In addition, these cells differentiate into hundreds of different types with specific functions (liver cells, nerve cells, muscle cells, etc.). A multitude of regulatory processes, both genetically and environmentally controlled, accomplish this differentiation. Elucidation of the exquisite timing of these processes remains one of the great challenges of human biology.

Immunity is the ability of an individual to recognize the self molecules that make up ones own body and to distinguish them from such nonself molecules as those found in infectious microorganisms and toxins. This process has a prominent genetic component. Knowledge of the genetic and molecular basis of the mammalian immune system has increased in parallel with the explosive advances made in somatic cell and molecular genetics.

There are two major components of the immune system, both originating from the same precursor stem cells. The bursa component provides B lymphocytes, a class of white blood cells that, when appropriately stimulated, differentiate into plasma cells. These latter cells produce circulating soluble proteins called antibodies or immunoglobulins. Antibodies are produced in response to substances called antigens, most of which are foreign proteins or polysaccharides. An antibody molecule can recognize a specific antigen, combine with it, and initiate its destruction. This so-called humoral immunity is accomplished through a complicated series of interactions with other molecules and cells; some of these interactions are mediated by another group of lymphocytes, the T lymphocytes, which are derived from the thymus gland. Once a B lymphocyte has been exposed to a specific antigen, it remembers the contact so that future exposure will cause an accelerated and magnified immune reaction. This is a manifestation of what has been called immunological memory.

The thymus component of the immune system centres on the thymus-derived T lymphocytes. In addition to regulating the B cells in producing humoral immunity, the T cells also directly attack cells that display foreign antigens. This process, called cellular immunity, is of great importance in protecting the body against a variety of viruses as well as cancer cells. Cellular immunity is also the chief cause of the rejection of organ transplants. The T lymphocytes provide a complex network consisting of a series of helper cells (which are antigen-specific), amplifier cells, suppressor cells, and cytotoxic (killer) cells, all of which are important in immune regulation.

One of the central problems in understanding the genetics of the immune system has been in explaining the genetic regulation of antibody production. Immunobiologists have demonstrated that the system can produce well over one million specific antibodies, each corresponding to a particular antigen. It would be difficult to envisage that each antibody is encoded by a separate gene; such an arrangement would require a disproportionate share of the entire human genome. Recombinant DNA analysis has illuminated the mechanisms by which a limited number of immunoglobulin genes can encode this vast number of antibodies.

Each antibody molecule consists of several different polypeptide chainsthe light chains (L) and the longer heavy chains (H). The latter determine to which of five different classes (IgM, IgG, IgA, IgD, or IgE) an immunoglobulin belongs. Both the L and H chains are unique among proteins in that they contain constant and variable parts. The constant parts have relatively identical amino acid sequences in any given antibody. The variable parts, on the other hand, have different amino acid sequences in each antibody molecule. It is the variable parts, then, that determine the specificity of the antibody.

Recombinant DNA studies of immunoglobulin genes in mice have revealed that the light-chain genes are encoded in four separate parts in germ-line DNA: a leader segment (L), a variable segment (V), a joining segment (J), and a constant segment (C). These segments are widely separated in the DNA of an embryonic cell, but in a mature B lymphocyte they are found in relative proximity (albeit separated by introns). The mouse has more than 200 light-chain variable region genes, only one of which will be incorporated into the proximal sequence that codes for the antibody production in a given B lymphocyte. Antibody diversity is greatly enhanced by this system, as the V and J segments rearrange and assort randomly in each B-lymphocyte precursor cell. The mechanisms by which this DNA rearrangement takes place are not clear, but transposons are undoubtedly involved. Similar combinatorial processes take place in the genes that code for the heavy chains; furthermore, both the light-chain and heavy-chain genes can undergo somatic mutations to create new antibody-coding sequences. The net effect of these combinatorial and mutational processes enables the coding of millions of specific antibody molecules from a limited number of genes. It should be stressed, however, that each B lymphocyte can produce only one antibody. It is the B lymphocyte population as a whole that produces the tremendous variety of antibodies in humans and other mammals.

Plasma cell tumours (myelomas) have made it possible to study individual antibodies, since these tumours, which are descendants of a single plasma cell, produce one antibody in abundance. Another method of obtaining large amounts of a specific antibody is by fusing a B lymphocyte with a rapidly growing cancer cell. The resultant hybrid cell, known as a hybridoma, multiplies rapidly in culture. Since the antibodies obtained from hybridomas are produced by clones derived from a single lymphocyte, they are called monoclonal antibodies.

As has been stated, cellular immunity is mediated by T lymphocytes that can recognize infected body cells, cancer cells, and the cells of a foreign transplant. The control of cellular immune reactions is provided by a linked group of genes, known as the major histocompatibility complex (MHC). These genes code for the major histocompatibility antigens, which are found on the surface of almost all nucleated somatic cells. The major histocompatibility antigens were first discovered on the leukocytes (white blood cells) and are therefore usually referred to as the HLA (human leukocyte group A) antigens.

The advent of the transplantation of human organs in the 1950s made the question of tissue compatibility between donor and recipient of vital importance, and it was in this context that the HLA antigens and the MHC were elucidated. Investigators found that the MHC resides on the short arm of chromosome 6, on four closely associated sites designated HLA-A, HLA-B, HLA-C, and HLA-D. Each locus is highly polymorphic; i.e., each is represented by a great many alleles within the human gene pool. These alleles, like those of the ABO blood group system, are expressed in codominant fashion. Because of the large number of alleles at each HLA locus, there is an extremely low probability of any two individuals (other than siblings) having identical HLA genotypes. (Since a person inherits one chromosome 6 from each parent, siblings have a 25 percent probability of having received the same paternal and maternal chromosomes 6 and thus of being HLA matched.)

Although HLA antigens are largely responsible for the rejection of organ transplants, it is obvious that the MHC did not evolve to prevent the transfer of organs from one person to another. Indeed, information obtained from the histocompatibility complex in the mouse (which is very similar in its genetic organization to that of the human) suggests that a primary function of the HLA antigens is to regulate the number of specific cytotoxic T killer cells, which have the ability to destroy virus-infected cells and cancer cells.

More is known about the genetics of the blood than about any other human tissue. One reason for this is that blood samples can be easily secured and subjected to biochemical analysis without harm or major discomfort to the person being tested. Perhaps a more cogent reason is that many chemical properties of human blood display relatively simple patterns of inheritance.

Certain chemical substances within the red blood cells (such as the ABO and MN substances noted above) may serve as antigens. When cells that contain specific antigens are introduced into the body of an experimental animal such as a rabbit, the animal responds by producing antibodies in its own blood.

In addition to the ABO and MN systems, geneticists have identified about 14 blood-type gene systems associated with other chromosomal locations. The best known of these is the Rh system. The Rh antigens are of particular importance in human medicine. Curiously, however, their existence was discovered in monkeys. When blood from the rhesus monkey (hence the designation Rh) is injected into rabbits, the rabbits produce so-called Rh antibodies that will agglutinate not only the red blood cells of the monkey but the cells of a large proportion of human beings as well. Some people (Rh-negative individuals), however, lack the Rh antigen; the proportion of such persons varies from one human population to another. Akin to data concerning the ABO system, the evidence for Rh genes indicates that only a single chromosome locus (called r) is involved and is located on chromosome 1. At least 35 Rh alleles are known for the r location; basically the Rh-negative condition is recessive.

A medical problem may arise when a woman who is Rh-negative carries a fetus that is Rh-positive. The first such child may have no difficulty, but later similar pregnancies may produce severely anemic newborn infants. Exposure to the red blood cells of the first Rh-positive fetus appears to immunize the Rh-negative mother, that is, she develops antibodies that may produce permanent (sometimes fatal) brain damage in any subsequent Rh-positive fetus. Damage arises from the scarcity of oxygen reaching the fetal brain because of the severe destruction of red blood cells. Measures are available for avoiding the severe effects of Rh incompatibility by transfusions to the fetus within the uterus; however, genetic counselling before conception is helpful so that the mother can receive Rh immunoglobulin immediately after her first and any subsequent pregnancies involving an Rh-positive fetus. This immunoglobulin effectively destroys the fetal red blood cells before the mothers immune system is stimulated. The mother thus avoids becoming actively immunized against the Rh antigen and will not produce antibodies that could attack the red blood cells of a future Rh-positive fetus.

Human serum, the fluid portion of the blood that remains after clotting, contains various proteins that have been shown to be under genetic control. Study of genetic influences has flourished since the development of precise methods for separating and identifying serum proteins. These move at different rates under the impetus of an electrical field (electrophoresis), as do proteins from many other sources (e.g., muscle or nerve). Since the composition of a protein is specified by the structure of its corresponding gene, biochemical studies based on electrophoresis permit direct study of tissue substances that are only a metabolic step or two away from the genes themselves.

Electrophoretic studies have revealed that at least one-third of the human serum proteins occur in variant forms. Many of the serum proteins are polymorphic, occurring as two or more variants with a frequency of not less than 1 percent each in a population. Patterns of polymorphic serum protein variants have been used to determine whether twins are identical (as in assessing compatibility for organ transplants) or whether two individuals are related (as in resolving paternity suits). Whether the different forms have a selective advantage is not generally known.

Much attention in the genetics of substances in the blood has been centred on serum proteins called haptoglobins, transferrins (which transport iron), and gamma globulins (a number of which are known to immunize against infectious diseases). Haptoglobins appear to relate to two common alleles at a single chromosome locus; the mode of inheritance of the other two seems more complicated, about 18 kinds of transferrins having been described. Like blood-cell antigen genes, serum-protein genes are distributed worldwide in the human population in a way that permits their use in tracing the origin and migration of different groups of people.

Hundreds of variants of hemoglobin have been identified by electrophoresis, but relatively few are frequent enough to be called polymorphisms. Of the polymorphisms, the alleles for sickle-cell and thalassemia hemoglobins produce serious disease in homozygotes, whereas others (hemoglobins C, D, and E) do not. The sickle-cell polymorphism confers a selective advantage on the heterozygote living in a malarial environment; the thalassemia polymorphism provides a similar advantage.

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Human genetics | biology | Britannica.com

Human genetics | biology | Britannica.com

Human genetics, study of the inheritance of characteristics by children from parents. Inheritance in humans does not differ in any fundamental way from that in other organisms.

The study of human heredity occupies a central position in genetics. Much of this interest stems from a basic desire to know who humans are and why they are as they are. At a more practical level, an understanding of human heredity is of critical importance in the prediction, diagnosis, and treatment of diseases that have a genetic component. The quest to determine the genetic basis of human health has given rise to the field of medical genetics. In general, medicine has given focus and purpose to human genetics, so the terms medical genetics and human genetics are often considered synonymous.

Read More on This Topic

genetics: Human genetics

Some geneticists specialize in the hereditary processes of human genetics. Most of the emphasis is on understanding and treating genetic disease and genetically influenced ill health, areas collectively known as medical genetics. One broad area of activity is laboratory research dealing with the

A new era in cytogenetics, the field of investigation concerned with studies of the chromosomes, began in 1956 with the discovery by Jo Hin Tjio and Albert Levan that human somatic cells contain 23 pairs of chromosomes. Since that time the field has advanced with amazing rapidity and has demonstrated that human chromosome aberrations rank as major causes of fetal death and of tragic human diseases, many of which are accompanied by mental retardation. Since the chromosomes can be delineated only during mitosis, it is necessary to examine material in which there are many dividing cells. This can usually be accomplished by culturing cells from the blood or skin, since only the bone marrow cells (not readily sampled except during serious bone marrow disease such as leukemia) have sufficient mitoses in the absence of artificial culture. After growth, the cells are fixed on slides and then stained with a variety of DNA-specific stains that permit the delineation and identification of the chromosomes. The Denver system of chromosome classification, established in 1959, identified the chromosomes by their length and the position of the centromeres. Since then the method has been improved by the use of special staining techniques that impart unique light and dark bands to each chromosome. These bands permit the identification of chromosomal regions that are duplicated, missing, or transposed to other chromosomes.

Micrographs showing the karyotypes (i.e., the physical appearance of the chromosome) of a male and a female have been produced. In a typical micrograph the 46 human chromosomes (the diploid number) are arranged in homologous pairs, each consisting of one maternally derived and one paternally derived member. The chromosomes are all numbered except for the X and the Y chromosomes, which are the sex chromosomes. In humans, as in all mammals, the normal female has two X chromosomes and the normal male has one X chromosome and one Y chromosome. The female is thus the homogametic sex, as all her gametes normally have one X chromosome. The male is heterogametic, as he produces two types of gametesone type containing an X chromosome and the other containing a Y chromosome. There is good evidence that the Y chromosome in humans, unlike that in Drosophila, is necessary (but not sufficient) for maleness.

A human individual arises through the union of two cells, an egg from the mother and a sperm from the father. Human egg cells are barely visible to the naked eye. They are shed, usually one at a time, from the ovary into the oviducts (fallopian tubes), through which they pass into the uterus. Fertilization, the penetration of an egg by a sperm, occurs in the oviducts. This is the main event of sexual reproduction and determines the genetic constitution of the new individual.

Human sex determination is a genetic process that depends basically on the presence of the Y chromosome in the fertilized egg. This chromosome stimulates a change in the undifferentiated gonad into that of the male (a testicle). The gonadal action of the Y chromosome is mediated by a gene located near the centromere; this gene codes for the production of a cell surface molecule called the H-Y antigen. Further development of the anatomic structures, both internal and external, that are associated with maleness is controlled by hormones produced by the testicle. The sex of an individual can be thought of in three different contexts: chromosomal sex, gonadal sex, and anatomic sex. Discrepancies between these, especially the latter two, result in the development of individuals with ambiguous sex, often called hermaphrodites. The phenomenon of homosexuality is of uncertain cause and is unrelated to the above sex-determining factors. It is of interest that in the absence of a male gonad (testicle) the internal and external sex anatomy is always female, even in the absence of a female ovary. A female without ovaries will, of course, be infertile and will not experience any of the female developmental changes normally associated with puberty. Such a female will often have Turners syndrome.

If X-containing and Y-containing sperm are produced in equal numbers, then according to simple chance one would expect the sex ratio at conception (fertilization) to be half boys and half girls, or 1 : 1. Direct observation of sex ratios among newly fertilized human eggs is not yet feasible, and sex-ratio data are usually collected at the time of birth. In almost all human populations of newborns, there is a slight excess of males; about 106 boys are born for every100 girls. Throughout life, however, there is a slightly greater mortality of males; this slowly alters the sex ratio until, beyond the age of about 50 years, there is an excess of females. Studies indicate that male embryos suffer a relatively greater degree of prenatal mortality, so the sex ratio at conception might be expected to favour males even more than the 106 : 100 ratio observed at birth would suggest. Firm explanations for the apparent excess of male conceptions have not been established; it is possible that Y-containing sperm survive better within the female reproductive tract, or they may be a little more successful in reaching the egg in order to fertilize it. In any case, the sex differences are small, the statistical expectation for a boy (or girl) at any single birth still being close to one out of two.

During gestationthe period of nine months between fertilization and the birth of the infanta remarkable series of developmental changes occur. Through the process of mitosis, the total number of cells changes from 1 (the fertilized egg) to about 2 1011. In addition, these cells differentiate into hundreds of different types with specific functions (liver cells, nerve cells, muscle cells, etc.). A multitude of regulatory processes, both genetically and environmentally controlled, accomplish this differentiation. Elucidation of the exquisite timing of these processes remains one of the great challenges of human biology.

Immunity is the ability of an individual to recognize the self molecules that make up ones own body and to distinguish them from such nonself molecules as those found in infectious microorganisms and toxins. This process has a prominent genetic component. Knowledge of the genetic and molecular basis of the mammalian immune system has increased in parallel with the explosive advances made in somatic cell and molecular genetics.

There are two major components of the immune system, both originating from the same precursor stem cells. The bursa component provides B lymphocytes, a class of white blood cells that, when appropriately stimulated, differentiate into plasma cells. These latter cells produce circulating soluble proteins called antibodies or immunoglobulins. Antibodies are produced in response to substances called antigens, most of which are foreign proteins or polysaccharides. An antibody molecule can recognize a specific antigen, combine with it, and initiate its destruction. This so-called humoral immunity is accomplished through a complicated series of interactions with other molecules and cells; some of these interactions are mediated by another group of lymphocytes, the T lymphocytes, which are derived from the thymus gland. Once a B lymphocyte has been exposed to a specific antigen, it remembers the contact so that future exposure will cause an accelerated and magnified immune reaction. This is a manifestation of what has been called immunological memory.

The thymus component of the immune system centres on the thymus-derived T lymphocytes. In addition to regulating the B cells in producing humoral immunity, the T cells also directly attack cells that display foreign antigens. This process, called cellular immunity, is of great importance in protecting the body against a variety of viruses as well as cancer cells. Cellular immunity is also the chief cause of the rejection of organ transplants. The T lymphocytes provide a complex network consisting of a series of helper cells (which are antigen-specific), amplifier cells, suppressor cells, and cytotoxic (killer) cells, all of which are important in immune regulation.

One of the central problems in understanding the genetics of the immune system has been in explaining the genetic regulation of antibody production. Immunobiologists have demonstrated that the system can produce well over one million specific antibodies, each corresponding to a particular antigen. It would be difficult to envisage that each antibody is encoded by a separate gene; such an arrangement would require a disproportionate share of the entire human genome. Recombinant DNA analysis has illuminated the mechanisms by which a limited number of immunoglobulin genes can encode this vast number of antibodies.

Each antibody molecule consists of several different polypeptide chainsthe light chains (L) and the longer heavy chains (H). The latter determine to which of five different classes (IgM, IgG, IgA, IgD, or IgE) an immunoglobulin belongs. Both the L and H chains are unique among proteins in that they contain constant and variable parts. The constant parts have relatively identical amino acid sequences in any given antibody. The variable parts, on the other hand, have different amino acid sequences in each antibody molecule. It is the variable parts, then, that determine the specificity of the antibody.

Recombinant DNA studies of immunoglobulin genes in mice have revealed that the light-chain genes are encoded in four separate parts in germ-line DNA: a leader segment (L), a variable segment (V), a joining segment (J), and a constant segment (C). These segments are widely separated in the DNA of an embryonic cell, but in a mature B lymphocyte they are found in relative proximity (albeit separated by introns). The mouse has more than 200 light-chain variable region genes, only one of which will be incorporated into the proximal sequence that codes for the antibody production in a given B lymphocyte. Antibody diversity is greatly enhanced by this system, as the V and J segments rearrange and assort randomly in each B-lymphocyte precursor cell. The mechanisms by which this DNA rearrangement takes place are not clear, but transposons are undoubtedly involved. Similar combinatorial processes take place in the genes that code for the heavy chains; furthermore, both the light-chain and heavy-chain genes can undergo somatic mutations to create new antibody-coding sequences. The net effect of these combinatorial and mutational processes enables the coding of millions of specific antibody molecules from a limited number of genes. It should be stressed, however, that each B lymphocyte can produce only one antibody. It is the B lymphocyte population as a whole that produces the tremendous variety of antibodies in humans and other mammals.

Plasma cell tumours (myelomas) have made it possible to study individual antibodies, since these tumours, which are descendants of a single plasma cell, produce one antibody in abundance. Another method of obtaining large amounts of a specific antibody is by fusing a B lymphocyte with a rapidly growing cancer cell. The resultant hybrid cell, known as a hybridoma, multiplies rapidly in culture. Since the antibodies obtained from hybridomas are produced by clones derived from a single lymphocyte, they are called monoclonal antibodies.

As has been stated, cellular immunity is mediated by T lymphocytes that can recognize infected body cells, cancer cells, and the cells of a foreign transplant. The control of cellular immune reactions is provided by a linked group of genes, known as the major histocompatibility complex (MHC). These genes code for the major histocompatibility antigens, which are found on the surface of almost all nucleated somatic cells. The major histocompatibility antigens were first discovered on the leukocytes (white blood cells) and are therefore usually referred to as the HLA (human leukocyte group A) antigens.

The advent of the transplantation of human organs in the 1950s made the question of tissue compatibility between donor and recipient of vital importance, and it was in this context that the HLA antigens and the MHC were elucidated. Investigators found that the MHC resides on the short arm of chromosome 6, on four closely associated sites designated HLA-A, HLA-B, HLA-C, and HLA-D. Each locus is highly polymorphic; i.e., each is represented by a great many alleles within the human gene pool. These alleles, like those of the ABO blood group system, are expressed in codominant fashion. Because of the large number of alleles at each HLA locus, there is an extremely low probability of any two individuals (other than siblings) having identical HLA genotypes. (Since a person inherits one chromosome 6 from each parent, siblings have a 25 percent probability of having received the same paternal and maternal chromosomes 6 and thus of being HLA matched.)

Although HLA antigens are largely responsible for the rejection of organ transplants, it is obvious that the MHC did not evolve to prevent the transfer of organs from one person to another. Indeed, information obtained from the histocompatibility complex in the mouse (which is very similar in its genetic organization to that of the human) suggests that a primary function of the HLA antigens is to regulate the number of specific cytotoxic T killer cells, which have the ability to destroy virus-infected cells and cancer cells.

More is known about the genetics of the blood than about any other human tissue. One reason for this is that blood samples can be easily secured and subjected to biochemical analysis without harm or major discomfort to the person being tested. Perhaps a more cogent reason is that many chemical properties of human blood display relatively simple patterns of inheritance.

Certain chemical substances within the red blood cells (such as the ABO and MN substances noted above) may serve as antigens. When cells that contain specific antigens are introduced into the body of an experimental animal such as a rabbit, the animal responds by producing antibodies in its own blood.

In addition to the ABO and MN systems, geneticists have identified about 14 blood-type gene systems associated with other chromosomal locations. The best known of these is the Rh system. The Rh antigens are of particular importance in human medicine. Curiously, however, their existence was discovered in monkeys. When blood from the rhesus monkey (hence the designation Rh) is injected into rabbits, the rabbits produce so-called Rh antibodies that will agglutinate not only the red blood cells of the monkey but the cells of a large proportion of human beings as well. Some people (Rh-negative individuals), however, lack the Rh antigen; the proportion of such persons varies from one human population to another. Akin to data concerning the ABO system, the evidence for Rh genes indicates that only a single chromosome locus (called r) is involved and is located on chromosome 1. At least 35 Rh alleles are known for the r location; basically the Rh-negative condition is recessive.

A medical problem may arise when a woman who is Rh-negative carries a fetus that is Rh-positive. The first such child may have no difficulty, but later similar pregnancies may produce severely anemic newborn infants. Exposure to the red blood cells of the first Rh-positive fetus appears to immunize the Rh-negative mother, that is, she develops antibodies that may produce permanent (sometimes fatal) brain damage in any subsequent Rh-positive fetus. Damage arises from the scarcity of oxygen reaching the fetal brain because of the severe destruction of red blood cells. Measures are available for avoiding the severe effects of Rh incompatibility by transfusions to the fetus within the uterus; however, genetic counselling before conception is helpful so that the mother can receive Rh immunoglobulin immediately after her first and any subsequent pregnancies involving an Rh-positive fetus. This immunoglobulin effectively destroys the fetal red blood cells before the mothers immune system is stimulated. The mother thus avoids becoming actively immunized against the Rh antigen and will not produce antibodies that could attack the red blood cells of a future Rh-positive fetus.

Human serum, the fluid portion of the blood that remains after clotting, contains various proteins that have been shown to be under genetic control. Study of genetic influences has flourished since the development of precise methods for separating and identifying serum proteins. These move at different rates under the impetus of an electrical field (electrophoresis), as do proteins from many other sources (e.g., muscle or nerve). Since the composition of a protein is specified by the structure of its corresponding gene, biochemical studies based on electrophoresis permit direct study of tissue substances that are only a metabolic step or two away from the genes themselves.

Electrophoretic studies have revealed that at least one-third of the human serum proteins occur in variant forms. Many of the serum proteins are polymorphic, occurring as two or more variants with a frequency of not less than 1 percent each in a population. Patterns of polymorphic serum protein variants have been used to determine whether twins are identical (as in assessing compatibility for organ transplants) or whether two individuals are related (as in resolving paternity suits). Whether the different forms have a selective advantage is not generally known.

Much attention in the genetics of substances in the blood has been centred on serum proteins called haptoglobins, transferrins (which transport iron), and gamma globulins (a number of which are known to immunize against infectious diseases). Haptoglobins appear to relate to two common alleles at a single chromosome locus; the mode of inheritance of the other two seems more complicated, about 18 kinds of transferrins having been described. Like blood-cell antigen genes, serum-protein genes are distributed worldwide in the human population in a way that permits their use in tracing the origin and migration of different groups of people.

Hundreds of variants of hemoglobin have been identified by electrophoresis, but relatively few are frequent enough to be called polymorphisms. Of the polymorphisms, the alleles for sickle-cell and thalassemia hemoglobins produce serious disease in homozygotes, whereas others (hemoglobins C, D, and E) do not. The sickle-cell polymorphism confers a selective advantage on the heterozygote living in a malarial environment; the thalassemia polymorphism provides a similar advantage.

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Human mitochondrial genetics – Wikipedia

Human mitochondrial genetics is the study of the genetics of human mitochondrial DNA (the DNA contained in human mitochondria). The human mitochondrial genome is the entirety of hereditary information contained in human mitochondria. Mitochondria are small structures in cells that generate energy for the cell to use, and are hence referred to as the “powerhouses” of the cell.

Mitochondrial DNA (mtDNA) is not transmitted through nuclear DNA (nDNA). In humans, as in most multicellular organisms, mitochondrial DNA is inherited only from the mother’s ovum. There are theories, however, that paternal mtDNA transmission in humans can occur under certain circumstances.[1]

Mitochondrial inheritance is therefore non-Mendelian, as Mendelian inheritance presumes that half the genetic material of a fertilized egg (zygote) derives from each parent.

Eighty percent of mitochondrial DNA codes for mitochondrial RNA, and therefore most mitochondrial DNA mutations lead to functional problems, which may be manifested as muscle disorders (myopathies).

Because they provide 30 molecules of ATP per glucose molecule in contrast to the 2 ATP molecules produced by glycolysis, mitochondria are essential to all higher organisms for sustaining life. The mitochondrial diseases are genetic disorders carried in mitochondrial DNA, or nuclear DNA coding for mitochondrial components. Slight problems with any one of the numerous enzymes used by the mitochondria can be devastating to the cell, and in turn, to the organism.

In humans, mitochondrial DNA (mtDNA) forms closed circular molecules that contain 16,569[2][3] DNA base pairs,[4] with each such molecule normally containing a full set of the mitochondrial genes. Each human mitochondrion contains, on average, approximately 5 such mtDNA molecules, with the quantity ranging between 1 and 15.[4] Each human cell contains approximately 100 mitochondria, giving a total number of mtDNA molecules per human cell of approximately 500.[4]

Because mitochondrial diseases (diseases due to malfunction of mitochondria) can be inherited both maternally and through chromosomal inheritance, the way in which they are passed on from generation to generation can vary greatly depending on the disease. Mitochondrial genetic mutations that occur in the nuclear DNA can occur in any of the chromosomes (depending on the species). Mutations inherited through the chromosomes can be autosomal dominant or recessive and can also be sex-linked dominant or recessive. Chromosomal inheritance follows normal Mendelian laws, despite the fact that the phenotype of the disease may be masked.

Because of the complex ways in which mitochondrial and nuclear DNA “communicate” and interact, even seemingly simple inheritance is hard to diagnose. A mutation in chromosomal DNA may change a protein that regulates (increases or decreases) the production of another certain protein in the mitochondria or the cytoplasm; this may lead to slight, if any, noticeable symptoms. On the other hand, some devastating mtDNA mutations are easy to diagnose because of their widespread damage to muscular, neural, and/or hepatic tissues (among other high-energy and metabolism-dependent tissues) and because they are present in the mother and all the offspring.

Mitochondrial genome mutations are passed on 100% of the time from mother to all her offspring. So, if a female has a mitochondrial trait, all offspring inherit it. However, if a male has a mitochondrial trait, no offspring inherit it.The number of affected mtDNA molecules inherited by a specific offspring can vary greatly because

It is possible, even in twin births, for one baby to receive more than half mutant mtDNA molecules while the other twin may receive only a tiny fraction of mutant mtDNA molecules with respect to wildtype (depending on how the twins divide from each other and how many mutant mitochondria happen to be on each side of the division). In a few cases, some mitochondria or a mitochondrion from the sperm cell enters the oocyte but paternal mitochondria are actively decomposed.

Genes in the human mitochondrial genome are as follows.

It was originally incorrectly believed that the mitochondrial genome contained only 13 protein-coding genes, all of them encoding proteins of the electron transport chain. However, in 2001, a 14th biologically active protein called humanin was discovered, and was found to be encoded by the mitochondrial gene MT-RNR2 which also encodes part of the mitochondrial ribosome (made out of RNA):

Unlike the other proteins, humanin does not remain in the mitochondria, and interacts with the rest of the cell and cellular receptors. Humanin can protect brain cells by inhibiting apoptosis. Despite its name, versions of humanin also exist in other animals, such as rattin in rats.

The following genes encode rRNAs:

The following genes encode tRNAs:

Mitochondrial DNA had traditionally had the two strand of the DNA designated the heavy and the light strand, due to their boyant densities during separation in cesium chloride gradients[5][6], which was found to be related to the relative G+T nucleotide content of the strand[7]. However, confusion of labeling of this strands is widespread, and appears to originate with a identification of the majority coding strand as the heavy in one influential article in 1999[8][7]. In humans, the light strand of mtDNA carries 28 genes and the heavy strand of mtDNA carries only 9 genes.[7][9] Eight of the 9 genes on the heavy strand code for mitochondrial tRNA molecules. Human mtDNA consists of 16,569 nucleotide pairs. The entire molecule is regulated by only one regulatory region which contains the origins of replication of both heavy and light strands. The entire human mitochondrial DNA molecule has been mapped[1][2].

The genetic code is, for the most part, universal, with few exceptions: mitochondrial genetics includes some of these. For most organisms the “stop codons” are “UAA”, “UAG”, and “UGA”. In vertebrate mitochondria “AGA” and “AGG” are also stop codons, but not “UGA”, which codes for tryptophan instead. “AUA” codes for isoleucine in most organisms but for methionine in vertebrate mitochondrial mRNA.

There are many other variations among the codes used by other mitochondrial m/tRNA, which happened not to be harmful to their organisms, and which can be used as a tool (along with other mutations among the mtDNA/RNA of different species) to determine relative proximity of common ancestry of related species. (The more related two species are, the more mtDNA/RNA mutations will be the same in their mitochondrial genome).

Using these techniques, it is estimated that the first mitochondria arose around 1.5 billion years ago. A generally accepted hypothesis is that mitochondria originated as an aerobic prokaryote in a symbiotic relationship within an anaerobic eukaryote.

Mitochondrial replication is controlled by nuclear genes and is specifically suited to make as many mitochondria as that particular cell needs at the time.

Mitochondrial transcription in humans is initiated from three promoters, H1, H2, and L (heavy strand 1, heavy strand 2, and light strand promoters). The H2 promoter transcribes almost the entire heavy strand and the L promoter transcribes the entire light strand. The H1 promoter causes the transcription of the two mitochondrial rRNA molecules.[10]

When transcription takes place on the heavy strand a polycistronic transcript is created. The light strand produces either small transcripts, which can be used as primers, or one long transcript. The production of primers occurs by processing of light strand transcripts with the Mitochondrial RNase MRP (Mitochondrial RNA Processing). The requirement of transcription to produce primers links the process of transcription to mtDNA replication. Full length transcripts are cut into functional tRNA, rRNA, and mRNA molecules.[citation needed]

The process of transcription initiation in mitochondria involves three types of proteins: the mitochondrial RNA polymerase (POLRMT), mitochondrial transcription factor A (TFAM), and mitochondrial transcription factors B1 and B2 (TFB1M, TFB2M). POLRMT, TFAM, and TFB1M or TFB2M assemble at the mitochondrial promoters and begin transcription. The actual molecular events that are involved in initiation are unknown, but these factors make up the basal transcription machinery and have been shown to function in vitro.[citation needed]

Mitochondrial translation is still not very well understood. In vitro translations have still not been successful, probably due to the difficulty of isolating sufficient mt mRNA, functional mt rRNA, and possibly because of the complicated changes that the mRNA undergoes before it is translated.[citation needed]

The Mitochondrial DNA Polymerase (Pol gamma, encoded by the POLG gene) is used in the copying of mtDNA during replication. Because the two (heavy and light) strands on the circular mtDNA molecule have different origins of replication, it replicates in a D-loop mode. One strand begins to replicate first, displacing the other strand. This continues until replication reaches the origin of replication on the other strand, at which point the other strand begins replicating in the opposite direction. This results in two new mtDNA molecules. Each mitochondrion has several copies of the mtDNA molecule and the number of mtDNA molecules is a limiting factor in mitochondrial fission. After the mitochondrion has enough mtDNA, membrane area, and membrane proteins, it can undergo fission (very similar to that which bacteria use) to become two mitochondria. Evidence suggests that mitochondria can also undergo fusion and exchange (in a form of crossover) genetic material among each other. Mitochondria sometimes form large matrices in which fusion, fission, and protein exchanges are constantly occurring. mtDNA shared among mitochondria (despite the fact that they can undergo fusion).[citation needed]

Mitochondrial DNA is susceptible to damage from free oxygen radicals from mistakes that occur during the production of ATP through the electron transport chain. These mistakes can be caused by genetic disorders, cancer, and temperature variations. These radicals can damage mtDNA molecules or change them, making it hard for mitochondrial polymerase to replicate them. Both cases can lead to deletions, rearrangements, and other mutations. Recent evidence has suggested that mitochondria have enzymes that proofread mtDNA and fix mutations that may occur due to free radicals. It is believed that a DNA recombinase found in mammalian cells is also involved in a repairing recombination process. Deletions and mutations due to free radicals have been associated with the aging process. It is believed that radicals cause mutations which lead to mutant proteins, which in turn led to more radicals. This process takes many years and is associated with some aging processes involved in oxygen-dependent tissues such as brain, heart, muscle, and kidney. Auto-enhancing processes such as these are possible causes of degenerative diseases including Parkinson’s, Alzheimer’s, and coronary artery disease.[citation needed]

Because mitochondrial growth and fission are mediated by the nuclear DNA, mutations in nuclear DNA can have a wide array of effects on mtDNA replication. Despite the fact that the loci for some of these mutations have been found on human chromosomes, specific genes and proteins involved have not yet been isolated. Mitochondria need a certain protein to undergo fission. If this protein (generated by the nucleus) is not present, the mitochondria grow but they do not divide. This leads to giant, inefficient mitochondria. Mistakes in chromosomal genes or their products can also affect mitochondrial replication more directly by inhibiting mitochondrial polymerase and can even cause mutations in the mtDNA directly and indirectly. Indirect mutations are most often caused by radicals created by defective proteins made from nuclear DNA.[citation needed]

In total, the mitochondrion hosts about 3000 different types of proteins, but only about 13 of them are coded on the mitochondrial DNA. Most of the 3000 types of proteins are involved in a variety of processes other than ATP production, such as porphyrin synthesis. Only about 3% of them code for ATP production proteins. This means most of the genetic information coding for the protein makeup of mitochondria is in chromosomal DNA and is involved in processes other than ATP synthesis. This increases the chances that a mutation that will affect a mitochondrion will occur in chromosomal DNA, which is inherited in a Mendelian pattern. Another result is that a chromosomal mutation will affect a specific tissue due to its specific needs, whether those may be high energy requirements or a need for the catabolism or anabolism of a specific neurotransmitter or nucleic acid. Because several copies of the mitochondrial genome are carried by each mitochondrion (210 in humans), mitochondrial mutations can be inherited maternally by mtDNA mutations which are present in mitochondria inside the oocyte before fertilization, or (as stated above) through mutations in the chromosomes.[citation needed]

Mitochondrial diseases range in severity from asymptomatic to fatal, and are most commonly due to inherited rather than acquired mutations of mitochondrial DNA. A given mitochondrial mutation can cause various diseases depending on the severity of the problem in the mitochondria and the tissue the affected mitochondria are in. Conversely, several different mutations may present themselves as the same disease. This almost patient-specific characterization of mitochondrial diseases (see Personalized medicine) makes them very hard to accurately recognize, diagnose and trace. Some diseases are observable at or even before birth (many causing death) while others do not show themselves until late adulthood (late-onset disorders). This is because the number of mutant versus wildtype mitochondria varies between cells and tissues, and is continuously changing. Because cells have multiple mitochondria, different mitochondria in the same cell can have different variations of the mtDNA. This condition is referred to as heteroplasmy. When a certain tissue reaches a certain ratio of mutant versus wildtype mitochondria, a disease will present itself. The ratio varies from person to person and tissue to tissue (depending on its specific energy, oxygen, and metabolism requirements, and the effects of the specific mutation). Mitochondrial diseases are very numerous and different. Apart from diseases caused by abnormalities in mitochondrial DNA, many diseases are suspected to be associated in part by mitochondrial dysfunctions, such as diabetes mellitus, forms of cancer and cardiovascular disease, lactic acidosis, specific forms of myopathy, osteoporosis, Alzheimer’s disease, Parkinsons’s disease, stroke, male infertility and which are also believed to play a role in the aging process.[citation needed]

Human mtDNA can also be used to help identify individuals.[11] Forensic laboratories occasionally use mtDNA comparison to identify human remains, and especially to identify older unidentified skeletal remains. Although unlike nuclear DNA, mtDNA is not specific to one individual, it can be used in combination with other evidence (anthropological evidence, circumstantial evidence, and the like) to establish identification. mtDNA is also used to exclude possible matches between missing persons and unidentified remains.[12] Many researchers believe that mtDNA is better suited to identification of older skeletal remains than nuclear DNA because the greater number of copies of mtDNA per cell increases the chance of obtaining a useful sample, and because a match with a living relative is possible even if numerous maternal generations separate the two. American outlaw Jesse James’s remains were identified using a comparison between mtDNA extracted from his remains and the mtDNA of the son of the female-line great-granddaughter of his sister.[13] Similarly, the remains of Alexandra Feodorovna (Alix of Hesse), last Empress of Russia, and her children were identified by comparison of their mitochondrial DNA with that of Prince Philip, Duke of Edinburgh, whose maternal grandmother was Alexandra’s sister Victoria of Hesse.[14] Similarly to identify Emperor Nicholas II remains his mitochondrial DNA was compared with that of James Carnegie, 3rd Duke of Fife, whose maternal great-grandmother Alexandra of Denmark (Queen Alexandra) was sister of Nicholas II mother Dagmar of Denmark (Empress Maria Feodorovna).[15]

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Human mitochondrial genetics – Wikipedia

Human genetics | biology | Britannica.com

Human genetics, study of the inheritance of characteristics by children from parents. Inheritance in humans does not differ in any fundamental way from that in other organisms.

The study of human heredity occupies a central position in genetics. Much of this interest stems from a basic desire to know who humans are and why they are as they are. At a more practical level, an understanding of human heredity is of critical importance in the prediction, diagnosis, and treatment of diseases that have a genetic component. The quest to determine the genetic basis of human health has given rise to the field of medical genetics. In general, medicine has given focus and purpose to human genetics, so the terms medical genetics and human genetics are often considered synonymous.

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genetics: Human genetics

Some geneticists specialize in the hereditary processes of human genetics. Most of the emphasis is on understanding and treating genetic disease and genetically influenced ill health, areas collectively known as medical genetics. One broad area of activity is laboratory research dealing with the

A new era in cytogenetics, the field of investigation concerned with studies of the chromosomes, began in 1956 with the discovery by Jo Hin Tjio and Albert Levan that human somatic cells contain 23 pairs of chromosomes. Since that time the field has advanced with amazing rapidity and has demonstrated that human chromosome aberrations rank as major causes of fetal death and of tragic human diseases, many of which are accompanied by mental retardation. Since the chromosomes can be delineated only during mitosis, it is necessary to examine material in which there are many dividing cells. This can usually be accomplished by culturing cells from the blood or skin, since only the bone marrow cells (not readily sampled except during serious bone marrow disease such as leukemia) have sufficient mitoses in the absence of artificial culture. After growth, the cells are fixed on slides and then stained with a variety of DNA-specific stains that permit the delineation and identification of the chromosomes. The Denver system of chromosome classification, established in 1959, identified the chromosomes by their length and the position of the centromeres. Since then the method has been improved by the use of special staining techniques that impart unique light and dark bands to each chromosome. These bands permit the identification of chromosomal regions that are duplicated, missing, or transposed to other chromosomes.

Micrographs showing the karyotypes (i.e., the physical appearance of the chromosome) of a male and a female have been produced. In a typical micrograph the 46 human chromosomes (the diploid number) are arranged in homologous pairs, each consisting of one maternally derived and one paternally derived member. The chromosomes are all numbered except for the X and the Y chromosomes, which are the sex chromosomes. In humans, as in all mammals, the normal female has two X chromosomes and the normal male has one X chromosome and one Y chromosome. The female is thus the homogametic sex, as all her gametes normally have one X chromosome. The male is heterogametic, as he produces two types of gametesone type containing an X chromosome and the other containing a Y chromosome. There is good evidence that the Y chromosome in humans, unlike that in Drosophila, is necessary (but not sufficient) for maleness.

A human individual arises through the union of two cells, an egg from the mother and a sperm from the father. Human egg cells are barely visible to the naked eye. They are shed, usually one at a time, from the ovary into the oviducts (fallopian tubes), through which they pass into the uterus. Fertilization, the penetration of an egg by a sperm, occurs in the oviducts. This is the main event of sexual reproduction and determines the genetic constitution of the new individual.

Human sex determination is a genetic process that depends basically on the presence of the Y chromosome in the fertilized egg. This chromosome stimulates a change in the undifferentiated gonad into that of the male (a testicle). The gonadal action of the Y chromosome is mediated by a gene located near the centromere; this gene codes for the production of a cell surface molecule called the H-Y antigen. Further development of the anatomic structures, both internal and external, that are associated with maleness is controlled by hormones produced by the testicle. The sex of an individual can be thought of in three different contexts: chromosomal sex, gonadal sex, and anatomic sex. Discrepancies between these, especially the latter two, result in the development of individuals with ambiguous sex, often called hermaphrodites. The phenomenon of homosexuality is of uncertain cause and is unrelated to the above sex-determining factors. It is of interest that in the absence of a male gonad (testicle) the internal and external sex anatomy is always female, even in the absence of a female ovary. A female without ovaries will, of course, be infertile and will not experience any of the female developmental changes normally associated with puberty. Such a female will often have Turners syndrome.

If X-containing and Y-containing sperm are produced in equal numbers, then according to simple chance one would expect the sex ratio at conception (fertilization) to be half boys and half girls, or 1 : 1. Direct observation of sex ratios among newly fertilized human eggs is not yet feasible, and sex-ratio data are usually collected at the time of birth. In almost all human populations of newborns, there is a slight excess of males; about 106 boys are born for every100 girls. Throughout life, however, there is a slightly greater mortality of males; this slowly alters the sex ratio until, beyond the age of about 50 years, there is an excess of females. Studies indicate that male embryos suffer a relatively greater degree of prenatal mortality, so the sex ratio at conception might be expected to favour males even more than the 106 : 100 ratio observed at birth would suggest. Firm explanations for the apparent excess of male conceptions have not been established; it is possible that Y-containing sperm survive better within the female reproductive tract, or they may be a little more successful in reaching the egg in order to fertilize it. In any case, the sex differences are small, the statistical expectation for a boy (or girl) at any single birth still being close to one out of two.

During gestationthe period of nine months between fertilization and the birth of the infanta remarkable series of developmental changes occur. Through the process of mitosis, the total number of cells changes from 1 (the fertilized egg) to about 2 1011. In addition, these cells differentiate into hundreds of different types with specific functions (liver cells, nerve cells, muscle cells, etc.). A multitude of regulatory processes, both genetically and environmentally controlled, accomplish this differentiation. Elucidation of the exquisite timing of these processes remains one of the great challenges of human biology.

Immunity is the ability of an individual to recognize the self molecules that make up ones own body and to distinguish them from such nonself molecules as those found in infectious microorganisms and toxins. This process has a prominent genetic component. Knowledge of the genetic and molecular basis of the mammalian immune system has increased in parallel with the explosive advances made in somatic cell and molecular genetics.

There are two major components of the immune system, both originating from the same precursor stem cells. The bursa component provides B lymphocytes, a class of white blood cells that, when appropriately stimulated, differentiate into plasma cells. These latter cells produce circulating soluble proteins called antibodies or immunoglobulins. Antibodies are produced in response to substances called antigens, most of which are foreign proteins or polysaccharides. An antibody molecule can recognize a specific antigen, combine with it, and initiate its destruction. This so-called humoral immunity is accomplished through a complicated series of interactions with other molecules and cells; some of these interactions are mediated by another group of lymphocytes, the T lymphocytes, which are derived from the thymus gland. Once a B lymphocyte has been exposed to a specific antigen, it remembers the contact so that future exposure will cause an accelerated and magnified immune reaction. This is a manifestation of what has been called immunological memory.

The thymus component of the immune system centres on the thymus-derived T lymphocytes. In addition to regulating the B cells in producing humoral immunity, the T cells also directly attack cells that display foreign antigens. This process, called cellular immunity, is of great importance in protecting the body against a variety of viruses as well as cancer cells. Cellular immunity is also the chief cause of the rejection of organ transplants. The T lymphocytes provide a complex network consisting of a series of helper cells (which are antigen-specific), amplifier cells, suppressor cells, and cytotoxic (killer) cells, all of which are important in immune regulation.

One of the central problems in understanding the genetics of the immune system has been in explaining the genetic regulation of antibody production. Immunobiologists have demonstrated that the system can produce well over one million specific antibodies, each corresponding to a particular antigen. It would be difficult to envisage that each antibody is encoded by a separate gene; such an arrangement would require a disproportionate share of the entire human genome. Recombinant DNA analysis has illuminated the mechanisms by which a limited number of immunoglobulin genes can encode this vast number of antibodies.

Each antibody molecule consists of several different polypeptide chainsthe light chains (L) and the longer heavy chains (H). The latter determine to which of five different classes (IgM, IgG, IgA, IgD, or IgE) an immunoglobulin belongs. Both the L and H chains are unique among proteins in that they contain constant and variable parts. The constant parts have relatively identical amino acid sequences in any given antibody. The variable parts, on the other hand, have different amino acid sequences in each antibody molecule. It is the variable parts, then, that determine the specificity of the antibody.

Recombinant DNA studies of immunoglobulin genes in mice have revealed that the light-chain genes are encoded in four separate parts in germ-line DNA: a leader segment (L), a variable segment (V), a joining segment (J), and a constant segment (C). These segments are widely separated in the DNA of an embryonic cell, but in a mature B lymphocyte they are found in relative proximity (albeit separated by introns). The mouse has more than 200 light-chain variable region genes, only one of which will be incorporated into the proximal sequence that codes for the antibody production in a given B lymphocyte. Antibody diversity is greatly enhanced by this system, as the V and J segments rearrange and assort randomly in each B-lymphocyte precursor cell. The mechanisms by which this DNA rearrangement takes place are not clear, but transposons are undoubtedly involved. Similar combinatorial processes take place in the genes that code for the heavy chains; furthermore, both the light-chain and heavy-chain genes can undergo somatic mutations to create new antibody-coding sequences. The net effect of these combinatorial and mutational processes enables the coding of millions of specific antibody molecules from a limited number of genes. It should be stressed, however, that each B lymphocyte can produce only one antibody. It is the B lymphocyte population as a whole that produces the tremendous variety of antibodies in humans and other mammals.

Plasma cell tumours (myelomas) have made it possible to study individual antibodies, since these tumours, which are descendants of a single plasma cell, produce one antibody in abundance. Another method of obtaining large amounts of a specific antibody is by fusing a B lymphocyte with a rapidly growing cancer cell. The resultant hybrid cell, known as a hybridoma, multiplies rapidly in culture. Since the antibodies obtained from hybridomas are produced by clones derived from a single lymphocyte, they are called monoclonal antibodies.

As has been stated, cellular immunity is mediated by T lymphocytes that can recognize infected body cells, cancer cells, and the cells of a foreign transplant. The control of cellular immune reactions is provided by a linked group of genes, known as the major histocompatibility complex (MHC). These genes code for the major histocompatibility antigens, which are found on the surface of almost all nucleated somatic cells. The major histocompatibility antigens were first discovered on the leukocytes (white blood cells) and are therefore usually referred to as the HLA (human leukocyte group A) antigens.

The advent of the transplantation of human organs in the 1950s made the question of tissue compatibility between donor and recipient of vital importance, and it was in this context that the HLA antigens and the MHC were elucidated. Investigators found that the MHC resides on the short arm of chromosome 6, on four closely associated sites designated HLA-A, HLA-B, HLA-C, and HLA-D. Each locus is highly polymorphic; i.e., each is represented by a great many alleles within the human gene pool. These alleles, like those of the ABO blood group system, are expressed in codominant fashion. Because of the large number of alleles at each HLA locus, there is an extremely low probability of any two individuals (other than siblings) having identical HLA genotypes. (Since a person inherits one chromosome 6 from each parent, siblings have a 25 percent probability of having received the same paternal and maternal chromosomes 6 and thus of being HLA matched.)

Although HLA antigens are largely responsible for the rejection of organ transplants, it is obvious that the MHC did not evolve to prevent the transfer of organs from one person to another. Indeed, information obtained from the histocompatibility complex in the mouse (which is very similar in its genetic organization to that of the human) suggests that a primary function of the HLA antigens is to regulate the number of specific cytotoxic T killer cells, which have the ability to destroy virus-infected cells and cancer cells.

More is known about the genetics of the blood than about any other human tissue. One reason for this is that blood samples can be easily secured and subjected to biochemical analysis without harm or major discomfort to the person being tested. Perhaps a more cogent reason is that many chemical properties of human blood display relatively simple patterns of inheritance.

Certain chemical substances within the red blood cells (such as the ABO and MN substances noted above) may serve as antigens. When cells that contain specific antigens are introduced into the body of an experimental animal such as a rabbit, the animal responds by producing antibodies in its own blood.

In addition to the ABO and MN systems, geneticists have identified about 14 blood-type gene systems associated with other chromosomal locations. The best known of these is the Rh system. The Rh antigens are of particular importance in human medicine. Curiously, however, their existence was discovered in monkeys. When blood from the rhesus monkey (hence the designation Rh) is injected into rabbits, the rabbits produce so-called Rh antibodies that will agglutinate not only the red blood cells of the monkey but the cells of a large proportion of human beings as well. Some people (Rh-negative individuals), however, lack the Rh antigen; the proportion of such persons varies from one human population to another. Akin to data concerning the ABO system, the evidence for Rh genes indicates that only a single chromosome locus (called r) is involved and is located on chromosome 1. At least 35 Rh alleles are known for the r location; basically the Rh-negative condition is recessive.

A medical problem may arise when a woman who is Rh-negative carries a fetus that is Rh-positive. The first such child may have no difficulty, but later similar pregnancies may produce severely anemic newborn infants. Exposure to the red blood cells of the first Rh-positive fetus appears to immunize the Rh-negative mother, that is, she develops antibodies that may produce permanent (sometimes fatal) brain damage in any subsequent Rh-positive fetus. Damage arises from the scarcity of oxygen reaching the fetal brain because of the severe destruction of red blood cells. Measures are available for avoiding the severe effects of Rh incompatibility by transfusions to the fetus within the uterus; however, genetic counselling before conception is helpful so that the mother can receive Rh immunoglobulin immediately after her first and any subsequent pregnancies involving an Rh-positive fetus. This immunoglobulin effectively destroys the fetal red blood cells before the mothers immune system is stimulated. The mother thus avoids becoming actively immunized against the Rh antigen and will not produce antibodies that could attack the red blood cells of a future Rh-positive fetus.

Human serum, the fluid portion of the blood that remains after clotting, contains various proteins that have been shown to be under genetic control. Study of genetic influences has flourished since the development of precise methods for separating and identifying serum proteins. These move at different rates under the impetus of an electrical field (electrophoresis), as do proteins from many other sources (e.g., muscle or nerve). Since the composition of a protein is specified by the structure of its corresponding gene, biochemical studies based on electrophoresis permit direct study of tissue substances that are only a metabolic step or two away from the genes themselves.

Electrophoretic studies have revealed that at least one-third of the human serum proteins occur in variant forms. Many of the serum proteins are polymorphic, occurring as two or more variants with a frequency of not less than 1 percent each in a population. Patterns of polymorphic serum protein variants have been used to determine whether twins are identical (as in assessing compatibility for organ transplants) or whether two individuals are related (as in resolving paternity suits). Whether the different forms have a selective advantage is not generally known.

Much attention in the genetics of substances in the blood has been centred on serum proteins called haptoglobins, transferrins (which transport iron), and gamma globulins (a number of which are known to immunize against infectious diseases). Haptoglobins appear to relate to two common alleles at a single chromosome locus; the mode of inheritance of the other two seems more complicated, about 18 kinds of transferrins having been described. Like blood-cell antigen genes, serum-protein genes are distributed worldwide in the human population in a way that permits their use in tracing the origin and migration of different groups of people.

Hundreds of variants of hemoglobin have been identified by electrophoresis, but relatively few are frequent enough to be called polymorphisms. Of the polymorphisms, the alleles for sickle-cell and thalassemia hemoglobins produce serious disease in homozygotes, whereas others (hemoglobins C, D, and E) do not. The sickle-cell polymorphism confers a selective advantage on the heterozygote living in a malarial environment; the thalassemia polymorphism provides a similar advantage.

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Human genetics | biology | Britannica.com

Basic Genetics

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Basic Genetics

National Human Genome Research Institute (NHGRI)

FDA recognizes NHGRI’s ClinGen, dataset that ties genetic variants to disease

For the first time, the Food and Drug Administration has formally recognized a public dataset of genetic variants and their relationship to disease to help accelerate the development of reliable genetic tests. Genetic test makers, including those using next-gen sequencing, can use genetic variant information in the Clinical Genome Resource (ClinGen) to support clinical validity in premarket submissions to FDA. ClinGen is administered by the National Human Genome Research Institute, part of the National Institutes of Health, and is available via ClinVar.

Andy Baxevanis, Ph.D., a senior scientist leading the Computational Genomics Unit at the National Human Genome Research Institute (NHGRI), has been named a Fellow of the American Association for the Advancement of Science (AAAS). Dr. Baxevanis was recognized for his distinguished contributions to the field of comparative genomics, particularly for using computational approaches to study the molecular innovations driving diversity in early animal evolution.

In the November issue of The Genomics Landscape, NHGRI Director Dr. Eric Green highlights the 25th anniversary of NHGRI’s Intramural Research Program. Other topics include: ClinGen and ClinVar featured in a special issue of Human Mutation, NIH enacting a policy change for summary results from genomics studies, a request for information (RFA) on the proposed NIH Data Management and Sharing Policy, the NIH All of Us Program funding awards for genome sequencing centers, and more.

North Asians, including Mongolians and other Siberian ethnic groups, may be more closely related to Eastern and Northern Europeans – including the people of Finland – than previously thought, according to a new genomics study in Nature Genetics. The international team of researchers, including those from the National Human Genome Research Institute (NHGRI), made the connection by comparing the whole-genome sequences of 175 ethnic Mongolians to existing genetic variation data.

The National Institutes of Health has updated its Genomic Data Sharing Policy to again allow unrestricted access to genomic summary results for most of the studies it supports. These summary results come from analyzing pooled genomic data from multiple individuals together to generate a statistical result for the entire dataset. Such information can be a powerful tool for helping researchers determine which genomic variants potentially contribute to a disease or disorder. Read the blogpost co-authored by NHGRI Director Eric Green

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National Human Genome Research Institute (NHGRI)

Human genetics | biology | Britannica.com

Human genetics, study of the inheritance of characteristics by children from parents. Inheritance in humans does not differ in any fundamental way from that in other organisms.

The study of human heredity occupies a central position in genetics. Much of this interest stems from a basic desire to know who humans are and why they are as they are. At a more practical level, an understanding of human heredity is of critical importance in the prediction, diagnosis, and treatment of diseases that have a genetic component. The quest to determine the genetic basis of human health has given rise to the field of medical genetics. In general, medicine has given focus and purpose to human genetics, so the terms medical genetics and human genetics are often considered synonymous.

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genetics: Human genetics

Some geneticists specialize in the hereditary processes of human genetics. Most of the emphasis is on understanding and treating genetic disease and genetically influenced ill health, areas collectively known as medical genetics. One broad area of activity is laboratory research dealing with the

A new era in cytogenetics, the field of investigation concerned with studies of the chromosomes, began in 1956 with the discovery by Jo Hin Tjio and Albert Levan that human somatic cells contain 23 pairs of chromosomes. Since that time the field has advanced with amazing rapidity and has demonstrated that human chromosome aberrations rank as major causes of fetal death and of tragic human diseases, many of which are accompanied by mental retardation. Since the chromosomes can be delineated only during mitosis, it is necessary to examine material in which there are many dividing cells. This can usually be accomplished by culturing cells from the blood or skin, since only the bone marrow cells (not readily sampled except during serious bone marrow disease such as leukemia) have sufficient mitoses in the absence of artificial culture. After growth, the cells are fixed on slides and then stained with a variety of DNA-specific stains that permit the delineation and identification of the chromosomes. The Denver system of chromosome classification, established in 1959, identified the chromosomes by their length and the position of the centromeres. Since then the method has been improved by the use of special staining techniques that impart unique light and dark bands to each chromosome. These bands permit the identification of chromosomal regions that are duplicated, missing, or transposed to other chromosomes.

Micrographs showing the karyotypes (i.e., the physical appearance of the chromosome) of a male and a female have been produced. In a typical micrograph the 46 human chromosomes (the diploid number) are arranged in homologous pairs, each consisting of one maternally derived and one paternally derived member. The chromosomes are all numbered except for the X and the Y chromosomes, which are the sex chromosomes. In humans, as in all mammals, the normal female has two X chromosomes and the normal male has one X chromosome and one Y chromosome. The female is thus the homogametic sex, as all her gametes normally have one X chromosome. The male is heterogametic, as he produces two types of gametesone type containing an X chromosome and the other containing a Y chromosome. There is good evidence that the Y chromosome in humans, unlike that in Drosophila, is necessary (but not sufficient) for maleness.

A human individual arises through the union of two cells, an egg from the mother and a sperm from the father. Human egg cells are barely visible to the naked eye. They are shed, usually one at a time, from the ovary into the oviducts (fallopian tubes), through which they pass into the uterus. Fertilization, the penetration of an egg by a sperm, occurs in the oviducts. This is the main event of sexual reproduction and determines the genetic constitution of the new individual.

Human sex determination is a genetic process that depends basically on the presence of the Y chromosome in the fertilized egg. This chromosome stimulates a change in the undifferentiated gonad into that of the male (a testicle). The gonadal action of the Y chromosome is mediated by a gene located near the centromere; this gene codes for the production of a cell surface molecule called the H-Y antigen. Further development of the anatomic structures, both internal and external, that are associated with maleness is controlled by hormones produced by the testicle. The sex of an individual can be thought of in three different contexts: chromosomal sex, gonadal sex, and anatomic sex. Discrepancies between these, especially the latter two, result in the development of individuals with ambiguous sex, often called hermaphrodites. The phenomenon of homosexuality is of uncertain cause and is unrelated to the above sex-determining factors. It is of interest that in the absence of a male gonad (testicle) the internal and external sex anatomy is always female, even in the absence of a female ovary. A female without ovaries will, of course, be infertile and will not experience any of the female developmental changes normally associated with puberty. Such a female will often have Turners syndrome.

If X-containing and Y-containing sperm are produced in equal numbers, then according to simple chance one would expect the sex ratio at conception (fertilization) to be half boys and half girls, or 1 : 1. Direct observation of sex ratios among newly fertilized human eggs is not yet feasible, and sex-ratio data are usually collected at the time of birth. In almost all human populations of newborns, there is a slight excess of males; about 106 boys are born for every100 girls. Throughout life, however, there is a slightly greater mortality of males; this slowly alters the sex ratio until, beyond the age of about 50 years, there is an excess of females. Studies indicate that male embryos suffer a relatively greater degree of prenatal mortality, so the sex ratio at conception might be expected to favour males even more than the 106 : 100 ratio observed at birth would suggest. Firm explanations for the apparent excess of male conceptions have not been established; it is possible that Y-containing sperm survive better within the female reproductive tract, or they may be a little more successful in reaching the egg in order to fertilize it. In any case, the sex differences are small, the statistical expectation for a boy (or girl) at any single birth still being close to one out of two.

During gestationthe period of nine months between fertilization and the birth of the infanta remarkable series of developmental changes occur. Through the process of mitosis, the total number of cells changes from 1 (the fertilized egg) to about 2 1011. In addition, these cells differentiate into hundreds of different types with specific functions (liver cells, nerve cells, muscle cells, etc.). A multitude of regulatory processes, both genetically and environmentally controlled, accomplish this differentiation. Elucidation of the exquisite timing of these processes remains one of the great challenges of human biology.

Immunity is the ability of an individual to recognize the self molecules that make up ones own body and to distinguish them from such nonself molecules as those found in infectious microorganisms and toxins. This process has a prominent genetic component. Knowledge of the genetic and molecular basis of the mammalian immune system has increased in parallel with the explosive advances made in somatic cell and molecular genetics.

There are two major components of the immune system, both originating from the same precursor stem cells. The bursa component provides B lymphocytes, a class of white blood cells that, when appropriately stimulated, differentiate into plasma cells. These latter cells produce circulating soluble proteins called antibodies or immunoglobulins. Antibodies are produced in response to substances called antigens, most of which are foreign proteins or polysaccharides. An antibody molecule can recognize a specific antigen, combine with it, and initiate its destruction. This so-called humoral immunity is accomplished through a complicated series of interactions with other molecules and cells; some of these interactions are mediated by another group of lymphocytes, the T lymphocytes, which are derived from the thymus gland. Once a B lymphocyte has been exposed to a specific antigen, it remembers the contact so that future exposure will cause an accelerated and magnified immune reaction. This is a manifestation of what has been called immunological memory.

The thymus component of the immune system centres on the thymus-derived T lymphocytes. In addition to regulating the B cells in producing humoral immunity, the T cells also directly attack cells that display foreign antigens. This process, called cellular immunity, is of great importance in protecting the body against a variety of viruses as well as cancer cells. Cellular immunity is also the chief cause of the rejection of organ transplants. The T lymphocytes provide a complex network consisting of a series of helper cells (which are antigen-specific), amplifier cells, suppressor cells, and cytotoxic (killer) cells, all of which are important in immune regulation.

One of the central problems in understanding the genetics of the immune system has been in explaining the genetic regulation of antibody production. Immunobiologists have demonstrated that the system can produce well over one million specific antibodies, each corresponding to a particular antigen. It would be difficult to envisage that each antibody is encoded by a separate gene; such an arrangement would require a disproportionate share of the entire human genome. Recombinant DNA analysis has illuminated the mechanisms by which a limited number of immunoglobulin genes can encode this vast number of antibodies.

Each antibody molecule consists of several different polypeptide chainsthe light chains (L) and the longer heavy chains (H). The latter determine to which of five different classes (IgM, IgG, IgA, IgD, or IgE) an immunoglobulin belongs. Both the L and H chains are unique among proteins in that they contain constant and variable parts. The constant parts have relatively identical amino acid sequences in any given antibody. The variable parts, on the other hand, have different amino acid sequences in each antibody molecule. It is the variable parts, then, that determine the specificity of the antibody.

Recombinant DNA studies of immunoglobulin genes in mice have revealed that the light-chain genes are encoded in four separate parts in germ-line DNA: a leader segment (L), a variable segment (V), a joining segment (J), and a constant segment (C). These segments are widely separated in the DNA of an embryonic cell, but in a mature B lymphocyte they are found in relative proximity (albeit separated by introns). The mouse has more than 200 light-chain variable region genes, only one of which will be incorporated into the proximal sequence that codes for the antibody production in a given B lymphocyte. Antibody diversity is greatly enhanced by this system, as the V and J segments rearrange and assort randomly in each B-lymphocyte precursor cell. The mechanisms by which this DNA rearrangement takes place are not clear, but transposons are undoubtedly involved. Similar combinatorial processes take place in the genes that code for the heavy chains; furthermore, both the light-chain and heavy-chain genes can undergo somatic mutations to create new antibody-coding sequences. The net effect of these combinatorial and mutational processes enables the coding of millions of specific antibody molecules from a limited number of genes. It should be stressed, however, that each B lymphocyte can produce only one antibody. It is the B lymphocyte population as a whole that produces the tremendous variety of antibodies in humans and other mammals.

Plasma cell tumours (myelomas) have made it possible to study individual antibodies, since these tumours, which are descendants of a single plasma cell, produce one antibody in abundance. Another method of obtaining large amounts of a specific antibody is by fusing a B lymphocyte with a rapidly growing cancer cell. The resultant hybrid cell, known as a hybridoma, multiplies rapidly in culture. Since the antibodies obtained from hybridomas are produced by clones derived from a single lymphocyte, they are called monoclonal antibodies.

As has been stated, cellular immunity is mediated by T lymphocytes that can recognize infected body cells, cancer cells, and the cells of a foreign transplant. The control of cellular immune reactions is provided by a linked group of genes, known as the major histocompatibility complex (MHC). These genes code for the major histocompatibility antigens, which are found on the surface of almost all nucleated somatic cells. The major histocompatibility antigens were first discovered on the leukocytes (white blood cells) and are therefore usually referred to as the HLA (human leukocyte group A) antigens.

The advent of the transplantation of human organs in the 1950s made the question of tissue compatibility between donor and recipient of vital importance, and it was in this context that the HLA antigens and the MHC were elucidated. Investigators found that the MHC resides on the short arm of chromosome 6, on four closely associated sites designated HLA-A, HLA-B, HLA-C, and HLA-D. Each locus is highly polymorphic; i.e., each is represented by a great many alleles within the human gene pool. These alleles, like those of the ABO blood group system, are expressed in codominant fashion. Because of the large number of alleles at each HLA locus, there is an extremely low probability of any two individuals (other than siblings) having identical HLA genotypes. (Since a person inherits one chromosome 6 from each parent, siblings have a 25 percent probability of having received the same paternal and maternal chromosomes 6 and thus of being HLA matched.)

Although HLA antigens are largely responsible for the rejection of organ transplants, it is obvious that the MHC did not evolve to prevent the transfer of organs from one person to another. Indeed, information obtained from the histocompatibility complex in the mouse (which is very similar in its genetic organization to that of the human) suggests that a primary function of the HLA antigens is to regulate the number of specific cytotoxic T killer cells, which have the ability to destroy virus-infected cells and cancer cells.

More is known about the genetics of the blood than about any other human tissue. One reason for this is that blood samples can be easily secured and subjected to biochemical analysis without harm or major discomfort to the person being tested. Perhaps a more cogent reason is that many chemical properties of human blood display relatively simple patterns of inheritance.

Certain chemical substances within the red blood cells (such as the ABO and MN substances noted above) may serve as antigens. When cells that contain specific antigens are introduced into the body of an experimental animal such as a rabbit, the animal responds by producing antibodies in its own blood.

In addition to the ABO and MN systems, geneticists have identified about 14 blood-type gene systems associated with other chromosomal locations. The best known of these is the Rh system. The Rh antigens are of particular importance in human medicine. Curiously, however, their existence was discovered in monkeys. When blood from the rhesus monkey (hence the designation Rh) is injected into rabbits, the rabbits produce so-called Rh antibodies that will agglutinate not only the red blood cells of the monkey but the cells of a large proportion of human beings as well. Some people (Rh-negative individuals), however, lack the Rh antigen; the proportion of such persons varies from one human population to another. Akin to data concerning the ABO system, the evidence for Rh genes indicates that only a single chromosome locus (called r) is involved and is located on chromosome 1. At least 35 Rh alleles are known for the r location; basically the Rh-negative condition is recessive.

A medical problem may arise when a woman who is Rh-negative carries a fetus that is Rh-positive. The first such child may have no difficulty, but later similar pregnancies may produce severely anemic newborn infants. Exposure to the red blood cells of the first Rh-positive fetus appears to immunize the Rh-negative mother, that is, she develops antibodies that may produce permanent (sometimes fatal) brain damage in any subsequent Rh-positive fetus. Damage arises from the scarcity of oxygen reaching the fetal brain because of the severe destruction of red blood cells. Measures are available for avoiding the severe effects of Rh incompatibility by transfusions to the fetus within the uterus; however, genetic counselling before conception is helpful so that the mother can receive Rh immunoglobulin immediately after her first and any subsequent pregnancies involving an Rh-positive fetus. This immunoglobulin effectively destroys the fetal red blood cells before the mothers immune system is stimulated. The mother thus avoids becoming actively immunized against the Rh antigen and will not produce antibodies that could attack the red blood cells of a future Rh-positive fetus.

Human serum, the fluid portion of the blood that remains after clotting, contains various proteins that have been shown to be under genetic control. Study of genetic influences has flourished since the development of precise methods for separating and identifying serum proteins. These move at different rates under the impetus of an electrical field (electrophoresis), as do proteins from many other sources (e.g., muscle or nerve). Since the composition of a protein is specified by the structure of its corresponding gene, biochemical studies based on electrophoresis permit direct study of tissue substances that are only a metabolic step or two away from the genes themselves.

Electrophoretic studies have revealed that at least one-third of the human serum proteins occur in variant forms. Many of the serum proteins are polymorphic, occurring as two or more variants with a frequency of not less than 1 percent each in a population. Patterns of polymorphic serum protein variants have been used to determine whether twins are identical (as in assessing compatibility for organ transplants) or whether two individuals are related (as in resolving paternity suits). Whether the different forms have a selective advantage is not generally known.

Much attention in the genetics of substances in the blood has been centred on serum proteins called haptoglobins, transferrins (which transport iron), and gamma globulins (a number of which are known to immunize against infectious diseases). Haptoglobins appear to relate to two common alleles at a single chromosome locus; the mode of inheritance of the other two seems more complicated, about 18 kinds of transferrins having been described. Like blood-cell antigen genes, serum-protein genes are distributed worldwide in the human population in a way that permits their use in tracing the origin and migration of different groups of people.

Hundreds of variants of hemoglobin have been identified by electrophoresis, but relatively few are frequent enough to be called polymorphisms. Of the polymorphisms, the alleles for sickle-cell and thalassemia hemoglobins produce serious disease in homozygotes, whereas others (hemoglobins C, D, and E) do not. The sickle-cell polymorphism confers a selective advantage on the heterozygote living in a malarial environment; the thalassemia polymorphism provides a similar advantage.

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Human genetics | biology | Britannica.com

The Human Microbiome – Learn.Genetics

APA format:

Genetic Science Learning Center. (2014, August 15) The Human Microbiome.Retrieved November 28, 2018, from https://learn.genetics.utah.edu/content/microbiome/

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The Human Microbiome [Internet]. Salt Lake City (UT): Genetic Science Learning Center; 2014[cited 2018 Nov 28] Available from https://learn.genetics.utah.edu/content/microbiome/

Chicago format:

Genetic Science Learning Center. “The Human Microbiome.” Learn.Genetics.August 15, 2014. Accessed November 28, 2018. https://learn.genetics.utah.edu/content/microbiome/.

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The Human Microbiome – Learn.Genetics

Dublin Aerospace

Dublin Aerospace is based at Dublin International Airport, Ireland. Our facility is 20,000m2 in size and covers Hangar 1, 4 and 5. We operate a 4 bay base maintenance facility that can presently handle approx 70 aircraft per annum, an APU overhaul centre that can handle 400 APUs a year and a Landing Gear services centre that has capacity for 250 legs annually.

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Dublin Aerospace


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