The 1000 Genomes Project to Study Human Genetic Variation to Support Disease Studies

The 1000 Genomes Project, led by an international research consortium, will
sequence the genomes of at least a thousand people from around the world to create the most detailed and medically useful picture to date of human genetic variation.

The international research consortium draws support from the Wellcome Trust Sanger Institute in Hinxton, England, the Beijing Genomics Institute, Shenzhen (BGI Shenzhen) in China and the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH).

The other participants include from as many as 35 Institutions such as the

Sanger Institute, BGI Shenzhen and National Human Genome Research Institute’s Large-Scale Sequencing Network,  Broad Institute of MIT and Harvard; the Washington University Genome Sequencing Centre at the Washington University School of Medicine in St. Louis; and the Human Genome Sequencing Centre at the Baylor College of Medicine in Houston. European Bioinformatics Institute near Cambridge, UK, and the National Centre for Biotechnology Information in the USA

Using standard DNA sequencing technologies, the effort would likely cost more than £250 million. However, leaders of the 1000 Genomes Project expect the costs to fall to as little as £15 million by the use of new sequencing technologies.

The scale is immense. At 6 trillion DNA bases, the 1000 Genomes Project will generate 60-fold more sequence data over its three-year course than have been deposited into public DNA databases over the past 25 years.

Among the populations whose DNA will be sequenced in the 1000 Genomes Project are: Yoruba in Ibadan, Nigeria; Japanese in Tokyo; Chinese in Beijing; Utah residents with ancestry from northern and western Europe; Luhya in Webuye, Kenya; Maasai in Kinyawa, Kenya; Toscani in Italy; Gujarati Indians in Houston; Chinese in metropolitan Denver; people of Mexican ancestry in Los Angeles; and people of African ancestry in the southwestern United States.

 

New Microarray technology replacing PCR and speed up HTS

Dr. Richard Gibbs, director of the Baylor College of Medicine Human Genome Sequencing Centre and his researchers along with the help of  NimbleGen Systems the  company recently acquired by Roche Applied Science has developed a new technique that combines gene chip technology with the latest generation of gene sequencing machines to allow fast and accurate sequencing of selected parts of the genome

 The technology, called “sequence capture,” enables fast and accurate enrichment of thousands of selected genomic regions, either contiguous or dispersed, such as segments of chromosomes or all genes or exons uses , The study had uses NimbleChip™ microarrays in preparation for a high-throughput 454 Sequencing™.

The study Direct Selection of Human Genomic Loci by Microarray Hybridization presented on October 10, 2007, at the J. Craig Venter Institute’s Genomes, Medicine, and the Environment (GME) conference, Roche NimbleGen and 454 Life Sciences, working with Dr. Richard , will create a whole-genome human exome (all exons) microarray, with the goal of resequencing the entire human exome faster and cheaper.

Till now researchers relied upon PCR for selection of specific genomic regions for resequencing

Limitations of PCR  meant the length of sequence it can amplify was small, is difficult to scale or multiplex for the enrichment of thousands of fragments, and has limited performance in the repetitive regions typical of complex genomes, such as human.

The sequence capture microarray technology bridges the gap between next-generation DNA sequencing technology and current sample preparation methods by providing an adaptable, massively parallel method for selective enrichment of genomic regions of interest.

The new process is simpler, more accurate and efficient than the multiplex PCR . In one experiment, more than 6,400 exons (the part of the genetic code that carries the instructions for making proteins), were analyzed. Using the old technology this would have taken at least six months.

So Thats how Humans Evolved! – Now we can begin to answer the big question

Which of the thousands of long stretches of repeated DNA in the human genome came first? And which are the duplicates the question have been answered by a team of scientists from University of Washington School of Medicine and University of California, San Diego.The research published by Evan Eichler from the University of Washington School of Medicine provide the first evolutionary history of the duplications in the human genome that are partly responsible for both disease and recent genetic innovations.

Evan Eichler has analyzed segmental duplications in the human genome and have successfully pinpointed the ancestral origin of each and identified the newly named core duplicon.

The study presents a comprehensive global analysis of the evolution of segmental duplications in the human enome. The authors identify the origin of ancestral duplication loci, regions of clustered duplicons, and evidence upporting a punctuated model of evolution.

This work marks a significant step toward a better understanding of what genomic changes paved the way for modern humans, when these duplications occurred and what the associated costs are – in terms of susceptibility to disease-causing genetic mutations.

Apart from the above study  the recently completed (check previous blogs) Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences the study helps to explain the evolutionary origins of human DNA and the role played by transposons

Genomes can duplicate long stretches of DNA from one chromosome and insert the duplication in another area of the genome. The resulting segments of DNA are called segmental duplications.  They are important because they hold evolutionary secrets

Finding answers to questions such as, Which set came first? What changes were innovated, when and why? What was sacrificed when an innovation took effect? What is the connection between disease and innovations within segmental duplications?, are important because researchers can then design specific medical treatments and can lead to ket discoveries in  Pharmacogenomics research

Download the Research Article

ENCODE consortium: forming background of why 3 billions bp are required for a human to survive not just the set of genes.

ENCODE consortium today published one in nature and 28 papers in genome research involving 35 groups from 80 organizations around the world, which promise to reshape our understanding of how the human genome functions. The findings totally challenge the tidy collection of independent genes , but sees as a complex networking system, along with regulatory elements and other types of DNA sequences that do not code for proteins, interact in overlapping ways not yet fully understood.

“This impressive effort has uncovered many exciting surprises and blazed the way for future efforts to explore the functional landscape of the entire human genome,” said NHGRI Director Francis S. Collins, M.D., Ph.D. “Because of the hard work and keen insights of the ENCODE consortium, the scientific community will need to rethink some long-held views about what genes are and what they do, as well as how the genome’s functional elements have evolved. This could have significant implications for efforts to identify the DNA sequences involved in many human diseases.”

Loads to come out of this …. few days back in nature cell biology there was a article stating small peptide regulators of actin-based cell morphogenesis encoded by a polycistronic mRNA in an eukaryote…

Future of High Throughput Genome Sequencing

In Bangalore Bio 2007 LabIndia has introduced  SOLiD: Sequencing by Oligonucleotide Ligation and Detection which is the Future of High Throughput Sequencing.

“This is useful for those who want to do full genome sequencing. Whole genome projects will be more cost effective with this new instrument than they are today,” said Dr. Anupama Gaur, Team Leader Application Support, Labindia Instruments, Pvt. Ltd.

HistoGenetics has come up with Sequence Based Typing which has many advantages such as identifying many rare and new alleles. “Nearly 2000 alleles have been identified so far and it has been launched in the US and UK as of now” said Dr. Cereb Nezih, M.D., President and co-founder, Histogenetics, Inc.

454 life sciences completes acquisition by Roche

BRANFORD, Conn., May 29, 2007 /PRNewswire/ — 454 Life Sciences announced today the completion of its acquisition by Roche Holdings, Inc. 454 Life Sciences, with its 167 employees, will remain in Branford, Connecticut as a member of the Roche Diagnostics organization.

The 454 Life Sciences, now part of Roche Diagnostics, and researchers from the Baylor College of Medicine (BCM) in Houston, US will present James Watson, co-discoverer of the DNA double helix and developer of the human genome project with his personal genome DNA sequence data at on May 31

related articles

eyeon DNA -Dr. Jim Watson’s Genome Sequenced for 2 Million Dollars

Geneengnews     curagen closes 454life sciences transaction

Microarrays in daily life

Accurate assessment of a calf’s future performance may soon be possible by using microarrays.

By 2010, less than three years away,
Australia’s largest integrated beef research program, the Beef Cooperative Research Centre (CRC) anticipates cattle breeders may be able to get an accurate assessment of a bull or a dam’s future performance within a few months of its birth

Professor John Gibson, Beef CRC Adaptation and Cattle Welfare Research Leader, says microarray technology has enabled the entire 23,000-odd separate genes of the bovine genome to be printed on one microarray plate the size of a microscope slide. 

“Research overseas indicates that how an animal expresses its genes in early life provides an accurate picture of its gene expression at breeding age.” 

This leads to the prospect of microarrays being printed that carry genes of commercial interest, which could be then used to predict the breeding performance of young animals well before they reach breeding age.

 Prof. Gibson observes that this would help breeders quickly eliminate genetically dud bulls and cows early in their life, without the costs of feeding and progeny testing now required to determine the duds. 

Genes add up risk of autoimmune disease

Geneticists have identified a link between the number of copies of a specific gene an individual has and their susceptibility to autoimmune diseases like lupus.

The research by Professor Tim Aitman of the Medical Research Council Clinical Sciences Centre at Imperial College London, and colleagues, is published in Nature Genetics.

From Medical News 

New approach to study microbiaL GENOTYPING

Over 99% of the Earth’s microorganisms cannot be cultivated in laboratory, making their ecological roles, biochemistry and potential practical applications an unresolved mystery. The cutting-edge approach to tackle this enigma, originally developed for the human genome sequencing project, has been sequencing large quantities of short sections of DNA from the extracts of entire microbial communities, and then assembling these sections back into individual genomes by computational means.

Unfortunately, the diversity of natural microbial communities proved so incredibly high, that very few genomes could be assembled from even the largest metagenomic studies, consisting of millions of DNA sequences.

In a paper published this month in the Proceedings of the National Academy of Sciences, Drs. Stepanauskas and Sieracki from Bigelow Laboratory for Ocean Sciences  propose an alternative to the metagenomic research.

The new method is based on fluorescence-activated sorting, whole genome amplification, and multi-locus DNA sequencing of single cells. This allows us to sequence any number of genes in each cell, including those that reveal cell’s identity and those that tell us what biochemical reactions the cell is capable of performing”, said Dr. Stepanauskas.

The publication “Matching phylogeny and metabolism in the uncultured marine bacteria, one cell at a time,” is a result of the researchers’ collaboration, 

The paper is available online at: PNAS

There is no ET in Human DNA

Well after all the hulllaba about the presence of extraterrestrial DNA in human genome and lots of blogs and articles later inlcuding the ones from mine which talked about the unusual presence and shift in genetic codon makeup in human DNA. More plausible evidence has started to emerge for what can be termed as ET DNA  in Human genome, triggered  by the completion of the genome sequencing of the marsupial opposum

An international team, led by researchers at the Broad Institute of MIT and Harvard, and supported by the National Institutes of Health (NIH), have announced the publication of the first genome of a marsupial, belonging to a South American species of opossum (Monodelphis domestica ). In a comparison of the marsupial genome to genomes of non-marsupials, including human, published in the journal Nature, the team found that most innovations leading to the human genome sequence lie not in protein-coding genes, but in areas that until recently were referred to as “junk” DNA. Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences the study helps to explain the evolutionary origins of human DNA and the role played by transposons,  

The study reveals a surprising role in human evolution for “jumping genes”

So how does the marsupial genome sequencing explains what has been refered as the presence of extraterrestrial gene or well of course we dont have any ET DNA

In the words of  Broad Institute director Eric Lander “Evolution is tinkering much more with the controls than it is with the genes themselves,”. “Almost all of the new innovation … is in the regulatory controls. In fact, marsupial mammals and placental mammals have largely the same set of protein-coding genes. But by contrast, 20 percent of the regulatory instructions in the human genome were invented after we parted ways with the marsupial.”

It showed that an important source of genetic innovation comes from bits of DNA, called transposons, that make up roughly half of our genome and that were previously thought to be genetic “junk.”

The research shows that this so-called junk DNA is anything but, and that it instead can help drive evolution by moving between chromosomes, turning genes on and off in new ways.

 “The official textbook picture of how genes work really didn’t appear to be right,” Lander said. “There was much more of the genome standing around shouting instructions than actually producing proteins.”

That raised a question of how evolution actually works on the genome, Lander said. With so much of the genome devoted to regulation, it became apparent that evolution could work by simply changing the instructions rather than changing the protein-coding genes themselves.

Now that perhaps explain all the articles you may have come across about the discovery of extraterrestrial genes in human DNA

Thus, the mobile elements that are typically thought of as “junk DNA” have played a creative role in genome evolution – spreading key genetic innovations involved in the control of gene expression across the genome.

 

A tiny opossum’s genome has shed light on how evolution creates new creatures from old, showing that change primarily comes by finding new ways of turning existing genes on and off

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