Daily Archives: September 24, 2012

Bangladeshi jute researchers are now upbeat at the prospect of commercial release of a new variety of jute -- Snow White Fibre -- following decoding of the genome of deadly fungus macrophomina phaseolina by a team of local scientists.

Globally famed geneticist Dr Maqsudul Alam led the team.

More than a decade ago, Bangladesh Jute Research Institute (BJRI) developed the jute variety with high commercial potentials but withheld its release to farmers considering its too much susceptibility to the deadly fungus -- macrophomina phaseolina.

BJRI breeders told The Daily Star that unlike other jute fibres, the fibres derived from Snow White variety do not require bleaching, and it has got all the potentials of being commercially used in threads, fabrics and garments.

"Its (Snow White) fibres could have been used alongside cotton at a 30-70 per cent ratio and it would have greatly reduced our import dependency for cotton. But after the invention of this special breeding line (Snow White), we found out that the variety is highly susceptive to macrophomina phaseolina," explained, biotechnologist Dr Shahidul Islam of BJRI.

Dr Islam, who was in the core team that Maqsudul Alam led in decoding the fungus genome, said despite all the potentials of the new jute variety, "We had to withhold its release to farmers because of fungi-susceptibility.

"Now that we traced out all the protein tools of macrophomina phaseolina and how it causes colossal damage to jute, in general, and this (Snow White) variety, in particular, we'll be able to engineer an immune system in the plant so that Snow White withstands the fungal damage."

Dr Islam went on, "We at BJRI even tried to develop a line (pre-variety stage) by cross-breeding Snow White with another line so that it no longer remains susceptive to macrophomina phaseolina. But that experiment in 2007 did not work as we ended up getting a line comparatively much less susceptive to the fungus but at the same time it lost many of the expected characteristics of Snow White line."

On Wednesday, Prime Minister Sheikh Hasina announced in parliament that Dr Alam and his team decoded the genome of the most deadly fungus that causes seedling blight, root rot and charcoal rot of more than 500 crop and non-crop species including jute and soybean.

The gene sequencing of macrophomina phaseolina would particularly help Bangladeshi scientists to develop jute varieties capable of fighting the fungus that causes an annual yield loss of around 40 billion taka (US$489.77 million) damaging 30 per cent of the country's precious natural fibre, experts said.

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Fungus genome map paves way for 'Snow White' jute variety

ScienceDaily (Sep. 23, 2012) A team of scientists with The Cancer Genome Atlas program reports their genetic characterization of 800 breast tumors, including finding some of the genetic causes of the most common forms of breast cancer, providing clues for new therapeutic targets, and identifying a molecular similarity between one sub-type of breast cancer and ovarian cancer.

Their findings, which offer a more comprehensive understanding of the mechanisms behind each sub-type of breast cancer, are reported in the Sept. 23, 2012 online edition of the journal Nature.

The researchers, including a large group from the University of North Carolina at Chapel Hill, analyzed tumors using two basic approaches: first, using an unbiased and genome-wide approach, and second, within the context of four previously known molecular sub-types of breast cancer: HER2-enriched, Luminal A, Luminal B and Basal-like. Both approaches arrived at the same conclusions, which suggest that even when given the tremendous genetic diversity of breast cancers, four main subtypes were observed. This study is also the first to integrate information from six analytic technologies, thus providing new insights into these previously defined disease subtypes.

Charles Perou, PhD, corresponding author of the paper, says, "Through the use of multiple different technologies, we were able to collect the most complete picture of breast cancer diversity ever. These studies have important implications for all breast cancer patients and confirm a large number of our previous findings. In particular, we now have a much better picture of the genetic causes of the most common form of breast cancer, namely Estrogen-Receptor positive/Luminal A disease. We also found a stunning similarity between Basal-like breast cancers and ovarian cancers."

"This study has now provided a near complete framework for the genetic causes of breast cancer, which will significantly impact clinical medicine in the coming years as these genetic markers are evaluated as possible markers of therapeutic responsiveness."

Dr. Perou is the May Goldman Shaw Distinguished Professor of Molecular Oncology and a member of UNC Lineberger Comprehensive Cancer Center.

Among the many discoveries include findings of some of the likely genetic causes of the most common form of breast cancer, which is the Estrogen-Receptor positive Luminal A subtype. Luminal A tumors are the number one cause of breast cancer deaths in the USA accounting for approximately 40 percent, and thus, finding the genetic drivers of this subtype is of paramount importance. The TCGA team found that the mutation diversity within this group was the greatest, and that even specific types of mutations within individual genes, were associated with the Luminal A subtype. Some of these mutations may be directly targetable by a drug(s) that is in clinical development, thus possibly offering new options for many patients.

In addition, the team compared basal-like breast tumors (also known as triple-negative breast cancers) with high-grade serous ovarian tumors and found many similarities at the molecular level, suggesting a related origin and similar therapeutic opportunities. These data also suggest that basal-like breast cancer should be considered a different disease than ER-positive/Luminal breast cancer, and in fact, both basal-like breast cancer and ovarian cancer were more similar to each other than either was to ER-positive/Luminal breast cancer.

Dr. Perou adds, "Cancer is, of course, a complex disease that includes many types of alterations, and thus, no one technology can identify all of these alteration; however, by using such a diverse and powerful set of technologies in a coordinated fashion, we were able to identify the vast majority of these alterations."

Katherine Hoadley, PhD, study co-author, explains, "Our ability to compare and integrate data from RNA, microRNA, mutations, protein, DNA methylation, and DNA copy number gave us a multitude of insights about breast cancer. In particular, highlighting how distinct basal-like breast cancers are from all other breast cancers on all data types. These findings suggest that basal-like breast cancer, while arising in the same anatomical location, is potentially a completely different disease."

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Cancer genome analysis of breast cancer: Team identifies genetic causes and similarity to ovarian cancer

The public got its first look at extensive genome research from the UW when the Encyclopedia of DNA Elements (ENCODE) released its findings to the public Sept. 5.

The UW has a rich history and promising future in genome studies. One of the five main data-generating centers for the Encyclopedia of DNA Elements (ENCODE) was in the UWs Genome Studies Department in the William H. Foege Building. Its findings were published in 30 articles spread across three science journals: Nature, Genome Biology, and Genome Research.

Planning for ENCODE started in 2003, just after the human genome was sequenced, but the project truly took off in 2007. The majority of the findings recently published came from work done between 2007 and 2012.

Some of the research for ENCODE involved what turns different kinds of cells on and off. Early in the project, researchers realized that each switch is different for each type of cell for example, the instructional on-switches for blue eyes and breast cancer are not the same.

In order to conduct the research, John Stamatoyannopoulos, M.D., UW associate professor and ENCODE researcher since 2003, had to create new technology. Stamatoyannopoulos and his team at the StamLab in the Foege Building were able to successfully map which genomes within a group regulate other genomes.

After treating the genomes with a chemical called nuclease, they discovered that little DNA fragments are released from these switches. The DNA splits directly where the regulatory genomes are located. Scientists can then collect them and use massive parallel sequencing to sequence and map hundreds of millions of these DNA pieces.

Scientists can then reconstruct exactly where the regulatory proteins are sitting in the switches. The reconstruction is full of connections and secondary, or tertiary, connections that end up looking like a neural network map.

The way these switches work, just to conceptualize it, is basically a string of letters, and you can think of them like a sentence, Stamatoyannopoulos said. The sentence is made up of words. These regulatory proteins come in and make these letters into specific words. Once these proteins all dock at a specific site, the gene is turned on.

Across the hall from the Stamlab is the Akey Lab, where Joshua Akey, Ph.D. and associate professor of genome sciences, and graduate student Benjamin Vernot worked on the history of human genomes.

They superimposed the ENCODE data with 52 known genome sequences gathered from geographically diverse areas and asked themselves basic questions such as whether or not an average individual has more protein-coding variation or variation that influences gene expression levels in populations. Understanding how patterns and variation are spread out among individuals and populations, or even species, and finding the evolutionary forces that act upon the sequence variation is what a population geneticist like Akey does.

Here is the original post:
Encoding the human genome

Public release date: 23-Sep-2012 [ | E-mail | Share ]

Contact: Dianne G. Shaw dgs@med.unc.edu 919-966-7834 University of North Carolina Health Care

A team of scientists with The Cancer Genome Atlas program reports their genetic characterization of 800 breast tumors, including finding some of the genetic causes of the most common forms of breast cancer, providing clues for new therapeutic targets, and identifying a molecular similarity between one sub-type of breast cancer and ovarian cancer.

Their findings, which offer a more comprehensive understanding of the mechanisms behind each sub-type of breast cancer, are reported in the September 23, 2012 online edition of the journal Nature.

The researchers, including a large group from the University of North Carolina at Chapel Hill, analyzed tumors using two basic approaches: first, using an unbiased and genome-wide approach, and second, within the context of four previously known molecular sub-types of breast cancer: HER2-enriched, Luminal A, Luminal B and Basal-like. Both approaches arrived at the same conclusions, which suggest that even when given the tremendous genetic diversity of breast cancers, four main subtypes were observed. This study is also the first to integrate information from six analytic technologies, thus providing new insights into these previously defined disease subtypes.

Charles Perou, PhD, corresponding author of the paper, says, "Through the use of multiple different technologies, we were able to collect the most complete picture of breast cancer diversity ever. These studies have important implications for all breast cancer patients and confirm a large number of our previous findings. In particular, we now have a much better picture of the genetic causes of the most common form of breast cancer, namely Estrogen-Receptor positive/Luminal A disease. We also found a stunning similarity between Basal-like breast cancers and ovarian cancers."

"This study has now provided a near complete framework for the genetic causes of breast cancer, which will significantly impact clinical medicine in the coming years as these genetic markers are evaluated as possible markers of therapeutic responsiveness."

Dr. Perou is the May Goldman Shaw Distinguished Professor of Molecular Oncology and a member of UNC Lineberger Comprehensive Cancer Center.

Among the many discoveries include findings of some of the likely genetic causes of the most common form of breast cancer, which is the Estrogen-Receptor positive Luminal A subtype. Luminal A tumors are the number one cause of breast cancer deaths in the USA accounting for approximately 40 percent, and thus, finding the genetic drivers of this subtype is of paramount importance. The TCGA team found that the mutation diversity within this group was the greatest, and that even specific types of mutations within individual genes, were associated with the Luminal A subtype. Some of these mutations may be directly targetable by a drug(s) that is in clinical development, thus possibly offering new options for many patients.

In addition, the team compared basal-like breast tumors (also known as triple-negative breast cancers) with high-grade serous ovarian tumors and found many similarities at the molecular level, suggesting a related origin and similar therapeutic opportunities. These data also suggest that basal-like breast cancer should be considered a different disease than ER-positive/Luminal breast cancer, and in fact, both basal-like breast cancer and ovarian cancer were more similar to each other than either was to ER-positive/Luminal breast cancer.

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UNC Lineberger scientists lead cancer genome analysis of breast cancer