Category Archives: Transhuman News

ENCODE 2020: Improving the syntax for understanding functional elements in the genome - Laurie Boyer
March 10-11, 2015 - From Genome Function to Biomedical Insight: ENCODE and Beyond More: http://www.genome.gov/27560819.

By: GenomeTV

View post:
ENCODE 2020: Improving the syntax for understanding functional elements in the genome - Laurie Boyer - Video

Additional suggestions related to genome function - Richard Myers
March 10-11, 2015 - From Genome Function to Biomedical Insight: ENCODE and Beyond More: http://www.genome.gov/27560819.

By: GenomeTV

Read more:
Additional suggestions related to genome function - Richard Myers - Video

The International Society for Stem Cell Research has released a statement calling for a moratorium on attempts to apply nuclear genome editing of the human germ line in clinical practice

In a statement released yesterday, the International Society for Stem Cell Research called for a moratorium on attempts at clinical application of nuclear genome editing of the human germ line to enable more extensive scientific analysis of the potential risks of genome editing and broader public discussion of the societal and ethical implications.

Technologies used to introduce changes into the DNA sequence of cells have advanced rapidly, making genome editing increasingly simple. Genome editing is feasible, not just in the somatic cells of an adult organism, but also in early embryos, as well as the gametes (sperm and egg) that carry the inheritable, germline DNA. Research involving germline nuclear genome editing has been performed to date in many organisms, including mice and monkeys, and applications to human embryos are possible.

The ISSCR statement raises significant ethical, societal and safety considerations related to the application of nuclear genome editing to the human germ line in clinical practice. Current genome editing technologies carry risks of unintended genome damage, in addition to unknown consequences. Moreover, consensus is lacking on what, if any, therapeutic applications of germ line genome modification might be permissible.

The statement calls for a moratorium on attempts to apply nuclear genome editing of the human germ line in clinical practice, as scientists currently lack an adequate understanding of the safety and potential long term risks of germline genome modification. Moreover, the ISSCR asserts that a deeper and more rigorous deliberation on the ethical, legal and societal implications of any attempts at modifying the human germ line is essential if its clinical practice is ever to be sanctioned.

In calling for the above moratorium, the ISSCR is not taking a position on the clinical testing of mitochondrial replacement therapy, a form of germline modification that entails replacing the mitochondria (found outside the nucleus) in the eggs of women at risk of transmitting certain devastating diseases to their children.

###

A full copy of the ISSCR statement is available at http://www.isscr.org/statement-on-human-germline-genome-modification.

About the International Society for Stem Cell Research:

The International Society for Stem Cell Research is an independent, nonprofit membership organization established to promote and foster the exchange and dissemination of information and ideas relating to stem cells, to encourage the general field of research involving stem cells and to promote professional and public education in all areas of stem cell research and application.

Originally posted here:
The ISSCR issues statement on human germline genome modification

Scientists also say that replacing a defective gene with a normal one may seem entirely harmless but perhaps would not be.

"We worry about people making changes without the knowledge of what those changes mean in terms of the overall genome," Dr. Baltimore said. "I personally think we are just not smart enough and won't be for a very long time to feel comfortable about the consequences of changing heredity, even in a single individual."

Many ethicists have accepted the idea of gene therapy, changes that die with the patient, but draw a clear line at altering the germline, since these will extend to future generations. The British Parliament in February approved the transfer of mitochondria, small DNA-containing organelles, to human eggs whose own mitochondria are defective. But that technique is less far-reaching because no genes are edited.

Read MoreFDA approves first DNA-based test for colon cancer

There are two broad schools of thought on modifying the human germline, said R. Alta Charo, a bioethicist at the University of Wisconsin and a member of the Doudna group. One is pragmatic and seeks to balance benefit and risk.

The other "sets up inherent limits on how much humankind should alter nature," she said. Some Christian doctrines oppose the idea of playing God, whereas in Judaism and Islam there is the notion "that humankind is supposed to improve the world." She described herself as more of a pragmatist, saying, "I would try to regulate such things rather than shut a new technology down at its beginning."

More here:
Scientists question editing of DNA

IMAGE:This is a diagram of chromosome shattering. view more

Credit: Mirjam de Pagter

The human genome can be very forgiving. When children inherit chromosomes from their parents, some minor genetic changes frequently occur with few, if any, consequences. One exception, as researchers report in the March 19 issue of the American Journal of Human Genetics, is chromosomal shattering, termed chromothripsis, which the authors found in healthy mothers who had each given birth to a severely affected child. The findings could have important implications for genetic testing and issues related to infertility.

"Our study shows that despite its dramatic effects on chromosomal architecture, chromothripsis--which involves shattering of one or multiple chromosomes followed by random reassembly--does not necessarily lead to disease," says senior author Wigard Kloosterman, PhD, of University Medical Center Utrecht, in The Netherlands. "However, the presence of this phenomenon in healthy individuals impacts reproduction by leading to difficulties getting pregnant, miscarriages, and the birth of children with multiple birth defects, including intellectual disability."

Dr. Kloosterman and his team studied three families whose children suffer from multiple abnormalities due to chromothripsis that they inherited from their mothers. Although the children's mothers were unaffected or only mildly affected, the women's genomes harbored even more genome breakage than their children's. Two of the mothers had experienced prior difficulties with getting pregnant, which was probably associated with their complex genomic rearrangements.

Although these results highlight the amazing ability of the human genome to tolerate gene disruption, they also indicate that chromothripsis can impact female reproduction and should be considered during counseling of couples dealing with infertility.

Dr. Kloosterman noted that it is difficult to estimate the frequency of chromothripsis in the general population, and many of the commonly used analytical techniques lack the resolution to detect it to its full extent. The chromothripsis in the three mothers in this study was balanced, meaning that there were no deletions or duplications (changes in the number of copies of a gene) of any of the genes that were rearranged. Two children inherited only a subset, rather than all, chromothripsis chromosomes from their mother. In the third family, an additional rearrangement occurred during chromosome transfer to the child. In all three children, the alterations resulted in deletions and duplications of chromosomal regions, which most likely explains the children's birth defects.

"If one would solely perform currently widely used array-based diagnostic tests for detecting the number of copies of a gene in these families, one would only detect the genomic defects in the children but fail to detect the changes in the mother," said Dr. Kloosterman. "This would lead to a substantial underestimation of the recurrence risk for future pregnancies." Therefore, it is important to use a combination of genetic screening techniques, preferably whole-genome sequencing, in certain cases, he explained.

###

This research was supported by the Child Health priority program from the University Medical Center Utrecht.

More here:
Chromosome shattering may be a hidden cause of birth defects

Photo: Andrew Brookes/Corbis

In 2005, next-generation sequencing began to change the field of genetics research. Obtaining a persons entire genome became fast and relatively cheap. Databases of genetic information were growing by the terabyte, and doctors and researchers were in desperate need of a way to efficiently sift through the information for the cause of a particular disorder or for clues to how patients might respond to treatment.

Companies have sprung up over the past five years that are vying to produce the first DNA search engine. All of them have different tacticssome even have their own proprietary databases of genetic informationbut most are working to link enough genetic databases so that users can quickly identify a huge variety of mutations. Most companies also craft search algorithms to supplement the genetic information with relevant biomedical literature. But as in the days of the early Web, before Google reigned supreme, a single company has yet to emerge as the clear winner.

Making a functional search engine is a classic big-data problem, says Michael Gonzalez, the vice president of bioinformatics at one such company, ViaGenetics, which was expected to relaunch its platform in March. Before doctors or researchers can use the data, genomic data must be organized so that humans can read and search it. The first step toward that is to put it in a standard form called the variant call format, or VCF. As raw data, a persons complete sequenced genome would take up about 100 gigabytes, so a database that adds the genomes of even 10 patients per day would quickly get out of hand. But VCF files are more compact, requiring only a few hundred megabytes per genome, which helps researchers find the specific variants they want to search in a fraction of the time. Unlike a fully sequenced genome, VCF files point only to where a persons genetic data deviates from the standardthe genome originally compiled by the Human Genome Project in 2001.

With VCF, sifting the genomes themselves for pinpoint mutations isnt the challenge for search engine companies. Most of these companies are allocating their resources toward efforts to seamlessly compile supplementary information about a specific mutation from other databases across the Web, such as the biomedical research archive PubMed or various troves of electronic medical records. Many of these tools have finely tuned algorithms that prioritize the results by credibility or relevance. You want to be able to pull together the information known about a mutation in that position [of the genome] and quickly make an assessment, says David Mittelman, the chief scientific officer for Tute Genomics, based in Provo, Utah, another company designing a genetic-search engine.

In an effort to expand the information that can be attached to a genome under examination, ViaGenetics, based in Miami Beach, Fla., is making its newly updated platform useful for researchers who want to collaborate across institutions. With ViaGenetics tools, researchers can make their data available to other users, so other people can come across these projects, request access, and form a collaboration, Gonzalez says. It helps people connect the dots between different researchers and institutions. This is especially helpful for smaller labs that may not have very extensive genome databases or for researchers from different universities working to decode the same mutation.

Although the genomic-search industry is now focused on serving scientists, that might not always be the case. Mittelman envisions that Tute Genomics could eventually serve consumers directly. People are already demanding information about their genomes just to understand themselves better, Mittelman says, but most companies dont yet consider the average person to be their primary customer. In order to make that shift, the tool will have to be even more intuitive and user-friendly. Fire-hosing someone with data thats not easy to interpret, or using terminology thats not standardized, has the potential to confuse people, he says. Privacy is also a major concern for the average user; the information that Tute users upload isnt stored permanently, Mittelman says, but users will need extra reassurance if the platform becomes available to the lay public.

And a further evolution of the industry is in the offing. Both ViaGenetics and Tute are hoping to be able to run the entire process in-housefrom the initial DNA sequencing to the presentation of final searchable results to users. The market for analyzing and interpreting genomic data is very fragmented, like the computer industry in the 1990s, where you had to go to separate providers to buy a video card or a motherboard and then try to put it together, Mittelman says. Soon this field will consolidate, as the computer industry did.

This article originally appeared in print as A Google for DNA.

Read the original post:
The Race to Build a Search Engine for Your DNA