Daily Archives: December 15, 2021

Human genetics is the study of how genetic, environmental, and behavioral factors, as well as their interactions, influence human traits, health, and disease. Public health genetics applies advances in human genetics and genomics to improve public health and prevent disease in diverse populations. Genetic counselors work as members of a health care team, providing information and support to patients with genetic disorders and those at risk for inherited conditions.

The Department of Human Genetics is dedicated to graduate training in human genetics research (including molecular, statistical, and bioinformatics research), public health genetics, and genetic counseling.

The mission of the department is to

Human genetics research has helped answer fundamental questions about human nature and led to the development of effective treatments for many diseases that greatly impact human health. Faculty in the Department of Human Genetics have developed and used genetic methods to investigate the causes and treatment of hereditary and acquired human illness and to understand and explore the impact of genetics on public health, education, and disease prevention.

Pitt Public Health human genetics faculty and students currently are involved in varied research projects, including...

Graduates of Pitt Public Healths human genetics program typically go on to positions in academia or in industry and usually are employed by their graduation dates. Alumni currently are working in academic, government, health care, and commercial sectors, including...

The Department of Human Genetics offers four masters level programs, and two doctoral programs:

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Human Genetics | Pitt Public Health | University of Pittsburgh

Genetic testing had its origins in the 1950s when scientists discovered that an additional copy of chromosome 21 causes Trisomy 21, also known as Down syndrome. Methods for staining chromosomes were used to sort and count chromosomes, a process called karyotyping. That process, combined with the ability to collect fetal cells from a pregnant womans amniotic fluid, provided scientists the ability to conduct genetic prenatal screening. Such testing revealed DNA-based diagnoses of genetic disorders caused by biologic irregularities such as too many chromosomes, too few, or clusters of chromosomes in the wrong places. As genetic testing became widespread, scientists began researching the substance of DNA, the chemical structure deciphered in 1953 by Rosalind Franklin, James Watson, and Francis Crick. Over the next several decades, it was discovered that helix-shaped patterns of paired chemical bases adenine, thymine, cytosine, and guanine provided a code that cells would decode into amino acids, the building blocks of protein. Scientists also discovered through research into the human genome that approximately 98% of DNA doesnt actually code for proteins, and was seen as junk DNA.

APPLICATION IN OBSTETRICS

As science around genetics developed, the application and use in obstetrics medicine also expanded. Many diseases that affect humans have a genetic component. Some disorders are passed from parents to their children at conception. A change in DNA sequence away from the normal sequence can result in a genetic disorder. Such genetic disorders can arise through mutation in one gene (monogenic disorder), mutations in multiple genes (multifactorial inheritance disorder), a combination of gene mutations and environmental factors, or by damage to chromosomes (changes in the number or structure of entire chromosomes, the structures that carry genes).

Advances in genetic mapping and technology have increased the accessibility and affordability of preconception carrier screening for couples considering pregnancy. Given the advanced reproductive technologies now available, preconception carrier screening allows a woman and her reproductive partner to make informed reproductive decisions.

Systemic genetic screening has been available in the United States since the 1960s, when Dr. Robert Guthrie developed the newborn screening test for phenylketonuria, a metabolic disorder also known as PKU. Since 1964, the Minnesota Department of Health has coordinated the screening of all newborns for more than 50 inherited or congenital disorders via a blood draw between 24 and 48 hours of birth. In 2010, the Recommended Uniform Screening Panel (RUSP) was adopted as a national standard for newborn screening, consisting of five main categories: (1) hemoglobinopathies, (2) organic acid disorders, (3) amino acid disorders, (4) fatty acid oxidation disorders, and (5) miscellaneous disorders, such as cystic fibrosis and hypothyroidism. The newborn screening program is the largest genetic screening program, with approximately 4 million infants tested annually. While the advances in newborn genetic screening programs have improved the detection and early intervention for treatable genetic conditions, newborn testing cannot replace preconception or early prenatal carrier screening of the parents.

Beginning in 2017, obstetricians were advised to expand genetic screening offerings to their patients. Two committee opinions from the American College of Obstetricians and Gynecologists (ACOG), published in the March 2017 issue of Obstetrics & Gynecology, expanded guidelines on carrier screening for genetic disorders. These committee opinions were issued in response to the availability and affordability of expanded genetic testing that could screen for hundreds of conditions in one test, as well as in response to dilution of ethnic population concentrations that had previously guided genetic screening recommendations. ACOG Committee Opinion 690, Carrier Screening in the Age of Genomic Medicine, includes general guidelines; and Committee Opinion 691, Carrier Screening for Genetic Conditions, addresses testing for specific diseases.

The committee opinions distinguish three scopes of genetic screening:

The general recommendation advises individual health care providers to establish a standard approach they offer consistently to patients, including counseling and informed consent. Counseling should include discussion of residual risk resulting from de novo mutations and mutations not included in test panels. At a minimum, the committee opinions advised that all patients should be offered screening for cystic fibrosis, spinal muscular atrophy, and hemoglobinopathies, because these are the more common recessive inherited conditions.

Advances in genetic science has led to the availability of preconception screening, offering couples seeking to become pregnant the opportunity to test for genetic changes that have little or no impact on their own health but can cause significant health problems for their children. ACOG defines carrier screening as genetic testing performed on an asymptomatic individual to determine whether that person has a mutation or abnormal allele within a gene that is associated with a particular disorder. Genetic changes carried by both partners can cause a health condition if both copies of the genetic change are inherited by a child. These are known as autosomal recessive conditions. Genetic changes that are carried by the female partner and cause a health condition when a male child inherits the genetic change are known as X-linked conditions.

Carrier testing is particularly valuable for consanguineous couples, whose offspring are at elevated risk of inheriting recessive mutations from shared ancestors. Prenatal carrier testing provides information for diagnostic testing of the fetus or newborn, for termination, or for arranging care.

Ideally, carrier screening should occur prior to pregnancy. If both partners are carriers for the same genetic condition, genetic counselling is recommended to help couples understand the meaning of the test results and the available reproductive options, such as in vitro fertilization (IVF) with prenatal diagnosis and preimplantation genetic testing of embryos, or the use of donor gametes.

Current guidelines by ACOG are that womens health care providers offer carrier screening to all individuals who express an interest in becoming pregnant, regardless of ethnicity or family history. Recent progress in genetic testing technology with next- generation sequencing makes expanded carrier screening readily accessible for most couples. Where couples present themselves for preconception health evaluations, a provider has a duty to inform of the availability and offer carrier screening. When genetic screening isnt offered to individuals seeking preconception evaluation, it is a deviation from accepted standards of care and could give rise under certain circumstances to a claim for wrongful conception.

With the added scientific knowledge gained through the National Institutes of Health Human Genome Project and spin-off research, we can expect to see continual expansion in applications for genetic science.

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The Evolution and Practical Application of Genetic Testing - Lexology

In these fractious times, when we are confronting the reality of systemic racism, how can we have an informed discussion about genetics and race?

One way is to calmly state the increasing evidence of meaningful genetic differences between human populations and then engage in honest and robust debate about the social and political implications, if any, of such inter-group divergence.

Back in the real world, meanwhile where open discussion of race and biology is largely taboo (a state of affairs recently exacerbated by DNA pioneer James Watson) a better idea might be to quickly change the subject. So what about the weather, eh?

But battening down the hatches and sitting out the storm isnt really an option. For a start, it would mean blithely ignoring the deluge of data from the recent revolution in molecular biology about our species evolution and of the genetic divergence of separate human populations over time. More importantly, it would also miss the opportunity to genuinely level the playing field for those very peoples most marginalised by an undeniable history of prejudice and neglect.

Note, though, the numerous alternatives for race already employed above: populations, groups, peoples (to which ancestry, descent and the like could also be added). Far from simply being politically correct euphemisms for a tainted term, it is important to distinguish between the word race as it is socially used say, the Black/African American, Native American, White, etc. racial categories used in the US census from the biological sense, used to describe distinct populations within a species.

Because of the historical misuse of the term race, this is an important distinction to make. In 19th century Britain, for example, two groups who would now be simply lumped together as White were regarded as separate biological races namely, and complete with the picturesque descriptors of the time, the careless, squalid, unaspiring Irish and the frugal, foreseeing, self-respecting Scots. (Full disclosure: my own genetic ancestry is of the careless, squalid and uninspiring variety.) A more modern perspective, however, does not deny the existence of genetically distinct indigenous British populations such groupings do indeed exist rather, it avoids describing them in meaningless racial terms. Similarly, the idea of an overarching Black race utterly fails to capture the genetic diversity of African (or African-descended) peoples, irrespective of how we are now able to distinguish genetically related groups within the wider human population of Africa.

Nor is this simply overly-sensitive quibbling over the meaning of a word. Historically, race was often used synonymously with varieties, breeds or sub-species (in the Descent of Man, for instance, Darwin considers at great length what was then still an open question: Arguments in favour of, and opposed to, ranking the so-called races of man as distinct species). But whether we like it or not, words have power, and once-acceptable descriptors of human inter-group variation now carry obvious egregious connotations (such as the slur half-breed).

Indeed, the limitations of language have long been a bane of everyday discussion of human evolution, with phrases and concepts survival of the fittest, say, or struggle for existence inevitably being interpreted in terms of intrinsic worth. Descriptions of sub-species of flora and fauna, for instance, would ruffle few feathers; similar talk of sub-populations of human beings, however, inevitably evokes hierarchical notions of superiority and inferiority. (As a light-heartened analogy, think of the hierarchical distinction between language and dialect then tell the Germans that their language is a dialect of Dutch.)

In sum, then, anyone discussing genetics and race must be conscious of the connotations and impact of words. And this is especially true when engaging in dialogue with those with a standard social science conception of race, one in which human evolved biology is seen as irrelevant to social issues a paradigm, moreover, in which the very idea of human biological difference is treated with the utmost suspicion. Given this latter mindset and the human tendency towards righteous indignation it is hardly surprising that many liberal-minded people react badly when confronted with arguments about human difference that they perceive (rightly or wrongly) as morally offensive. If worthwhile or meaningful discussion of genetics and race is to proceed, therefore, it is beholden on geneticists and their ilk to take this into account not through political timidity but through simple courtesy and common-sense.

Of course, as pointed out above, such is the toxic nature of this topic that open discussion is often avoided, especially by those cowed by the likely reaction of their peers. In this respect, political scientist James Flynn discoverer of the eponymous Flynn effect of rising IQ over time points to the counterproductive nature of intellectual censorship: [T]hose who boycott debate forfeit a chance to persuade. They have put their money on indoctrination and intimidation. A good bet in the short run but over the long course that horse never wins.

The sort of censorious indignation highlighted by Flynn also has another detrimental effect: it opens a space for nationalistic populists and race supremacists to claim they are simply telling it as it is or bravely saying what others are too scared to admit. The losers here, of course, are the very people that the taboos were designed to protect those marginalized minorities likely to face greater prejudice from emboldened bigots.

Moreover, Flynns own work provides a further explicit example of how such taboos can have counterproductive consequences; if Flynn had been unable to research the causes of reported racial differences in IQ he would never have discovered the Flynn effect, the best evidence we have of environmental influences on intelligence (and of how improvements in impoverished environments can lead to dramatic changes in IQ scores over time).

This points not only to the benefits of openly addressing sensitive subjects, but also to a possible way to assuage some of the suspicion that surrounds genetic research into inter-group difference that even if such differences are shown to exist, this does not dictate any particular social or political response. Facts do not determine values.

At the same time, however, facts can certainly inform social policy. Take, for example, the overwhelming evidence of strong genetic influences on academic achievement. Contrary to what many might pessimistically assume, this genetic evidence does not mean that nothing can be done for those currently failing in the education system. As the Flynn effect shows, environmental change does make a difference, despite the high heritability of IQ.

Indeed, the strong genetic determinants of educational attainment are much less straightforward than they appear. For example, some studies that indicate a causal link between genes and learning hinge on the observation that older mothers have offspring who are more likely to succeed in school. As older mothers also have fewer children (with whom they can devote more time and resources), the relevant genetic influence here pertains to fertility rather than academic smarts. Given this, and given a political desire to raise academic attainment amongst specific groups, ameliorative social policy could focus on womens reproductive health and opportunities in marginalised communities.

Be this as it may. The point is that genetic facts including evidence of genetic differences between racial populations carry no necessarily social or political implications. Nevertheless, these same genetic facts may help highlight obstacles to achieving desired social outcomes, and could provide information that assists in overcoming them. In this respect, just as greater awareness of social and environmental barriers can assist in designing policies to reduce inequalities, so too could greater recognition of possible genetic hurdles to improved life outcomes.

In the past in the era of Social Darwinism and eugenics hereditarian political beliefs equated biology with destiny. Unfortunately, much of the present-day antipathy to human genetic research appears premised on a similar erroneous belief: that if human behavior is under the influence of biology/genes then certain social outcomes, such as disparities in wealth or status, are inevitable. Hence the desire to denigrate genetic research that touches on the raw nerve of race for, as many well-intentioned egalitarians may mistakenly believe, if meaningful differences between different peoples really do exist, then the goal of greater equality could prove unattainable.

The biological study of human behavior is notoriously fraught hardly surprising, given that fallible humans are both the subject and the object of scrutiny. Furthermore, given the egregious history of political ideas based on supposed facts of human biology, the results of human behavioral research are often held to a higher standard of proof and most especially with research relating to politically sensitive topics, such as race, gender or sexuality.

Whether always warranted or not, such critical inspection comes with the territory; indeed, one higher standard that human geneticists can impose upon themselves is to understand the motivation of the opposition, however wrong-headed this might appear. Such awareness would not mean avoiding discussion of troublesome topics but it might avoid discussing them in ways more likely to inflame than inform.

A version of this article was originally published by the Genetic Literacy Project on Feb 13, 2019.

Patrick Whittle has a PhD in philosophy and is a freelance writer with a particular interest in the social and political implications of modern biological science. Follow him on his website patrickmichaelwhittle.com or on Twitter @WhittlePM

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Genetics and race: An awkward conversation during volatile times - Genetic Literacy Project

Ive admired the cockroachs ability to regrow lost legs since learning about them while working on my PhD in developmental genetics ages ago. Cut off a roachs appendage, and soon signals from the exposed cells stimulate division of neighboring cells at the injury site. And out grows a new leg.

The signaling pathways of both embryonic development and regeneration are common to many animal species, and are therefore ancient. The genes in control have intriguing names: Grainy Head, Notch, Wingless,Sonic Hedgehog,and evenHippo.

I remember reading about elegant experiments that moved the cells at the interface of an amputation in a model organism, such as the cockroach poster-child for regeneration. When a researcher rotated the cells at a cut site, a turned-around limb unfurled.

Salamanders can regenerate limbs too. Back in graduate school in Thom Kaufmans lab at Indiana University, we had two pet Mexican axolotls from the developmental biology group upstairs. Sally and Gerry Mander lived in a large rectangular tank above the vials of fruit flies, happily swimming, as amphibians do. And if a bit of a leg broke off from crashing into the side, the salamander could regrow it.

Of course humans cant regenerate missing limbs, or even toes. Our closest relatives that can are lizards (reptiles, not amphibians).

In a new report in Nature Communications, researchers from the Keck School of Medicine of USC and the University of Pittsburgh describe teaming the gene-editing tool CRISPR with neural stem cells to enable mourning geckos to regrow functional tails. Without the intervention, the lizards regrow tails that are bands of soft cartilage, good for little more than balance. A working tail is built of a distinctive top and bottom that spatially distributes nervous and muscle tissue in a pattern that enables the animal to move. The research has implications for regenerative medicine.

Growing a tail is complicated, and embryos are the experts.

Undulating levels of biochemical signals bathe the dividing cells of early embryos of any species. This highly regulated brew turns specific genes on and off in ways that direct the emergence of tissues that then interact and fold into organs.

In an animal species that has an amniote egg (surrounded by air, fluid, and membranes), the embryos tail develops from a bump called a tail bud. The cells then sort themselves into a top (dorsal) layer of roof plates and a bottom (ventral) layer of floor plates.

Thats what happens in an embryo as the choreography of development unfolds. But replacing a body part after injury to an adult isnt the same as the origin of the corresponding part in an embryo. And so an injured lizard can regrow something from an amputated tail, but its not the real deal. Instead, its a tube of cartilage that doesnt do much. (Imagine replacing a dogs wagging tail with a static cardboard tube.) The adult lizards replacement tail lacks the nuances that distinguish top from bottom, what developmental biologists call dorsoventral patterning. (Dorso refers to the back and ventral to the belly portion of a structure.)

The wounded lizard makes a cartilage tail because it inappropriately activates Sonic Hedgehog signaling. In the embryo, this signaling normally fades and that triggers harder bone to replace the bendy tail cartilage. At the same time, the stem cells that occupy the neural tube that forms along the embryos back divide and specialize, giving rise to the nerve cells of the spinal cord and dorsal root ganglia. A few stem cells remain in the adult, clinging to the interior of the spinal cord.

What would happen, the researchers wondered, if they blocked Sonic Hedgehog signaling in adult geckos with shortened tails? Would the stem cells step in to regenerate appendages that could enable movement, and not just offer the balance that a cartilage tail provides?

In the experiments, the researchers isolated neural stem cells from lizard embryos, used CRISPR/Cas9 gene editing to knock out the ability of the cells to respond to Sonic Hedgehog signaling. They then injected the disarmed stem cells into the spinal cords of adults that had their tails cut off.

The introduced cells indeed glommed onto the forming cartilage tail tubes and instead oversaw establishment of the dorsal-ventral, aka top-bottom, distinction that enabled the animals to regenerate complete and functioning tails not the placeholders. The new and improved lizard tails have bone and nerve tissue on the upper or dorsal side, and cartilage on the lower or ventral side.

Said co-author Thomas Lozito, an assistant professor of orthopedic surgery and stem cell biology and regenerative medicine at the Keck School of Medicine,

This is one of the only cases where the regeneration of an appendage has been significantly improved through stem cell-based therapy in any reptile, bird or mammal, and it informs efforts to improve wound healing in humans. Perfecting the imperfect regenerated lizard tail provides us with a blueprint for improving healing in wounds that dont naturally regenerate, such as severed human limbs and spinal cords. In this way, we hope our lizard research will lead to medical breakthroughs for treating hard-to-heal injuries.

Ricki Lewis has a PhD in genetics and is a science writer and author of several human genetics books.She is an adjunct professor for the Alden March Bioethics Institute at Albany Medical College.Follow her at herwebsiteor Twitter@rickilewis

A version of this article was originally posted atPLOSand has been reposted here with permission. PLOS can be found on Twitter@PLOS

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Regrowing limbs using CRISPR? It's been done with lizards, with hopes that human limb regeneration will be possible in the future - Genetic Literacy...

Do you go once a day? Maybe you go twice, or even three times? Or perhaps you only go a few times a week? Yes, were talking about pooing. In our new study, weve found how often you go is, at least to some degree, a function of your genetic make-up.

You might be wondering why this is something we chose to study. While many people rarely give a second thought to going when the urge presents itself, for others, common gastrointestinal conditions like irritable bowel syndrome (IBS) cause problems.

IBS affects up to 10 per cent of people globally and is characterised by abdominal pain and bloating, irregular bowel habits, constipation and diarrhoea. Although not life threatening, it can severely affect a persons quality of life.

We dont know exactly what causes IBS, which means therapeutic options are limited, mostly directed at treating the symptoms rather than targeting specific causes. We also dont have a way to tell who is at increased risk of IBS.

In this climate, our general research aims to identify genetic risk factors for IBS by looking at genomic information and health-related data across large groups of people. The idea is that our findings may, in time, pave the way towards better treatment options.

In our latest study, published in the journal Cell Genomics, we looked at how often people poo or their stool frequency and how this correlates with their genes. Our findings provide clues as to the genetic risk factors associated with IBS.

Investigating the genetic links for complex diseases such as IBS is challenging for a variety of reasons. One way to simplify things is to deconstruct the disease into individual biological components or traits related to the physiological processes disturbed during illness.

These are called intermediate phenotypes or endophenotypes. If you were looking at heart disease, blood pressure would be an example of an intermediate phenotype.

We took this approach in our research, and opted to study intestinal motility, or gut motility, as a hallmark intermediate phenotype of IBS. By way of background, many people with IBS experience intestinal dysmotility, which is when the gut doesnt work properly at moving its contents (such as food and drink) through the digestive system. This may result in symptoms including constipation or diarrhoea.

While direct measurement of gut motility in humans requires clinical procedures that are not suitable for large-scale studies, stool frequency has been shown to correlate with gut motility and may therefore be used as its proxy in big genetic studies.

On this basis, we analysed data from 167,875 people (taken from the UK Biobank and four smaller groups in Europe and the US) who provided information on how often they move their bowels.

Alongside this data, we analysed millions of DNA markers the building blocks of our DNA which make each of us genetically unique. We demonstrated for the first time that stool frequency is, at least in part, a heritable characteristic.

We identified 14 regions of the human genome where specific DNA markers occur more often in people reporting higher or lower stool frequency compared to the rest of the population. This makes sense, because within these regions are multiple genes whose products (including neurotransmitters, hormones and receptors) are involved in the communication between the gut and the brain.

While some of these molecules were already known, and have even been the targets of drugs to influence gut motility, most represent potential new candidates for the treatment of diarrhoea, constipation and IBS.

A common genetic denominator

We also found evidence of similar genetic architecture between stool frequency and IBS. In other words, the genetic factors important for controlling stool frequency appear to also be important when it comes to the risk of developing IBS.

Finally, we wanted to see whether what we learned in our study could be used to try to identify people at increased risk of IBS. We did this by calculating polygenic scores, which are numerical values summarising genetic information, in this case relating to the probability of having altered stool frequency.

This was more informative for IBS primarily characterised by diarrhoea. Using data from the UK Biobank, we showed that people with higher polygenic scores (therefore more likely to have higher stool frequency) are up to five times more likely to suffer from IBS with diarrhoea than the rest of the population.

Some limitations

Its important to point out that our study doesnt account for lifestyle and dietary factors, which certainly have an effect on bowel habits.

And while we identified 14 regions containing DNA markers important for stool frequency, within most of these regions, individual genes and their specific biological functions still need to be characterised.

Further, stool frequency polygenic scores and their value in predicting IBS need to be tested and validated in independent studies and among people from different ethnic backgrounds (only individuals of European ancestry were included in this research).

Overall, however, these are important initial genetic findings, which could help us identify new treatment options. They also open up the possibility of using genetic information to identify IBS patients, as well as those falling into specific subtypes (such as IBS characterised by diarrhoea). This in turn could help to stratify patients into appropriate treatment groups.

Mauro DAmato is Visiting Professor, Unit of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet. Ferdinando Bonfiglio is Research Associate, Unit of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet.

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How often do you poo? New research shows bowel habits are written in our DNA - The Indian Express

CU Cancer Center members James DeGregori, Ph.D., and Edward J. Evans, Ph.D., analyzed data to highlight the surprising abundance of cells with cancer-associated mutations in cancer-free individuals.

It's worth noting, in light of recently published research, that a majority of people won't be diagnosed with cancer in their lifetimes. According to the National Cancer Institute, about 40% of people will, which means 60% won't.

These percentages are worth remembering because research conducted by University of Colorado Cancer Center Deputy Director James DeGregori, Ph.D., a professor of biochemistry and molecular genetics, and Edward J. Evans, Ph.D., a postdoctoral fellow in the Department of Biochemistry and Molecular Genetics, found that most cancer-free individuals over age 60 carry at least 100 billion cells harboring at least one oncogenic, or tumor-causing, mutation.

The research, published in Aging and Cancer, involved a meta-analysis of previously published sequencing data on normal tissues, which DeGregori and Evans used to categorize somatic mutations, or mutations that occur after egg fertilization, based on their presence in cancer and showcase the quantity of cells with cancer-associated mutations in cancer-free individuals.

"When you have trillions of cells and they're being maintained for up to a century, they're going to accumulate mutations," DeGregori explains. "The fact that we get mutations is not surprising, just based on known mutation rates. One thing this research points to is that we need to start looking at these mutations, and how or whether they cause cancer, from a different light."

Gathering data to associate mutations with cancer

"To understand the genesis of cancer, we need to look at normal tissue," Evans says. "By the time it's developed into cancer, all the mutations are there and we don't always know which ones are contributing to the actual genesis of cancer.

"We had the idea that a lot of the mutations in people would be oncogenic or associated with cancer, but we just didn't know how many. We figured that it would increase as people get older, but we didn't necessarily know which genes would be prevalent and we didn't know the magnitude of how many cells could actually have these oncogenic mutations."

After reviewing existing literature, Evans collected datasets from researchers who previously had conducted research on mutations in normal tissue. He taught himself to code in the programming language Python so that he could pull appropriate data and create data frames to categorize mutations by the genes, tissue, and age of individuals in which they were occurring, among other factors.

"We have about three trillion nucleated cells in our bodies, so to put it in perspective, 100 billion cells with oncogenic mutations isn't a majority of our total number of cells," Evans says. "But that's a surprisingly high number considering that it only takes one cell to cause cancer. If there are billions of cells with these mutations but no indication of cancer, what does that mean? What does it mean to have these oncogenic mutations in the body?"

Understanding differences between tissue types

One of the interesting facets of the research findings, DeGregori says, has been learning that oncogenic mutations can be extremely prevalent in certain types of tissue, including skin, colon, and esophagus.

"Some tissues can be absolutely dominated by these mutations," DeGregori says. "But if you look at the esophagus, for example, half of it is loaded with NOTCH1 mutations, which rarely contribute to cancer in non-smokers. So, to test for this mutation isn't really useful if most of us have it and it rarely leads to cancer.

"If we're simply looking for oncogenic mutations, we're always going to find them and they may not tell us much about cancer risk. How those oncogenic mutations are interfacing with the tissue environment will tell us so much more about risk."

A further avenue of research, DeGregori says, will be studying why some tissues have such a high occurrence of oncogenic mutations but a comparatively low occurrence of cancer, while other types of tissue have a relatively low level of oncogenic mutations.

"Before we began this research, I had no idea that almost 90% of colon cells become occupied with cancer-causing mutations," DeGregori said. "That the number was so high was quite surprising, but a relatively low percentage of us will get colon cancer. So, it's going to be important to study this difference between tissue types. Why is it that epithelial tissue in the skin, for example, becomes dominated by oncogenic variants, but lung tissue actually keeps a fairly low level?"

Evans says future research could continue studying which oncogenic mutations are most likely to contribute to cancer and help to hone genetic screening tools to test for the most cancer-causing mutations.

"The vast majority of mutations don't do anything, they don't cause any problems, and many aren't even in coding sequences," DeGregori explains. "Every cell in our bodies has dozens and dozens of mutations, if not hundreds or thousands, so we have an opportunity to begin asking whether these patterns of mutations that we see can dictate whether someone is at high risk of cancer."

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Research Demonstrates That Cells With Cancer-Associated Mutations Overtake Human Tissue With Age - Anti Aging News