Genetic researchers have substantial advances in understanding the evolutionary causes of common diseases and human history, a series of reports published in scientific journals after this week.
The most important of these results is the work of an international consortium of over 200 scientists from Canada, China, Japan, Nigeria, United Kingdom and the United States in the October 27 issue of the journal Nature.
The team examinedDNA samples from four different parts of the world and concluded that genetic variants located physically close to each other are inherited together in groups called haplotypes. The complete catalog of all of these blocks is known as the HapMap. "
"Building on the basis of a fixed sequence of the human genome, the HapMap is a powerful new tool for research into the causes of common diseases," said David Altshuler, MD, PhD, program director inMedical Genetics and the population of Broad Institute of Harvard and MIT.
"Such understanding is necessary for researchers to develop new approaches and urgent to understand the causes of common diseases is still volatile, such as diabetes, bipolar disorder, cancer and many others," he adds.
Altshuler and Peter Donnelly, PhD, University of Oxford in England, are the corresponding authors of the journal Nature.
Greatest information as efficiently
E 'has long been known that diseases in the family, perhaps with half of the inherited risk of common diseases caused by genetic differences of the parents said. Heredity also plays a role in different responses to a drug or an environmental factor game.
Since the causes of these common diseases and treatment responses largely unknown - and because knowing this information is necessary for the successful development of new approaches to prevention, Diagnosis and treatment - identifying the genetic contributors to human health is a fundamental goal of biomedicine.
A new genomics-based approach to human genetics was proposed nearly a decade populations cataloging human DNA sequence variations and full of common test them systematically for their association with disease in humans.
Although it is theoretically possible to collect all this information by> Sequencing the human genome, all this is neither technically nor economically feasible.
"The data from the HapMap project, scientists in an efficient way to particular DNA variants, most of the information in the largest offering, reduce costs and improve performance of genetic research to identify the source of disease," says Mark Daly, an associate member of the Broad Institute of Harvard and MIT. Daly led the Boston team's statistical and analytical work, and was a member of the writing group for the journal Nature.
Millions of SNPs a day
In addition, the HapMap project helped spur a remarkable progress in technology for testing genetic variations in DNA, which enables you to undertake extensive studies in large patient samples.
A single nucleotide polymorphism, or SNP (pronounced "snip") is a small genetic change or changes, DNA that can occur within a person> Sequence.
"When we started this work, a number of years, to determine the genotype of a SNP in a patient cost nearly a dollar, and we have hundreds of blogs a day," said Stacey Gabriel, director of the Broad Institute Genetic Analysis Platform, and an author of the journal Nature.
"Today the prices, in many cases at a fraction of a cent for each genotype were killed, and we can make millions a day," says Gabriel. "This is the difference between not able to do the study,and get done quickly and well. "
Days SNPs
The HapMap provides excellent power to capture most human variation and link or other symptoms of the disease, according to a paper published in the genetic correlation of the November issue of Nature.
Paul de Bakker, Roman Yalensky and his colleagues have shown that the determination, through the development and evaluation of methods of "tag SNPs" that capture the genetic variation to select in any environment with a minimal amount of work.
WithThese tags, scientists can compare the SNP patterns of people affected by a disease with unaffected far more efficiently than was previously possible.
"Compared to directly genotyping all common SNPs in the genome in all individuals of a study of disease, we selected tag SNPs based on HapMap can save genotyping observed by almost an order of magnitude, without realizing that a lot of power in a club real, "says De Bakker, post-doctoral fellow in Altshuler and DalyGroup at the Broad Institute.
The widely used tool for tag SNP selection was developed by de Bakker and colleagues.
Previous computer models to simple
Another important observation that the availability of HapMap data to computer models of human genetics that is too simplistic and can lead to erroneous conclusions about previous diseases the role of different genes or genetic loci.
Stephen Schaffner, Altshuler and colleagues at the BroadInstitute to describe the limitations of these models, first published in an article in the November issue of Genome Research. They also provide the scientific community with updated models that come close in reality the empirical data generated by the HapMap Consortium.
Better computer models can be useful tools for understanding the nature of human DNA variation, past changes in human population size and evolutionary selection, "saysSchaffner, a computational biologist in the wide range of medical genetics and population.
The candidate for natural selection
The public availability of genome-wide differences in the HapMap data also allows scientists to conduct systematic studies of potential sites on the genome of natural selection in humans and also for evaluating new application for selection.
Pardis Sabet, Eric Lander and colleagues at the Broad Institute, together withStephen O'Brien and colleagues at the National Cancer Institute used the HapMap data to a major case of natural selection, the study reported in association with HIV infection.
A genetic variation in a T cell receptor, called CCR5-? 32, which confers a strong resistance to HIV infection because of the complex and was placed on the bubonic plague, rose up against resistance, recently in the human population, do not issue reports in the November PLoS Biology.
"With the advantage of greaterGenotyping and empirical comparisons from the HapMap, we were able to demonstrate that the pattern of genetic variation seen at CCR5-? 32 does not stand out as exceptional relative to other loci on the genome and is consistent with neutral evolution, "said Sabet, a postdoctoral fellow at the Broad Institute.
"In fact, CCR5 is? 32 allele probably arose more than 5,000 years, not accepted over the past 1,000 years since it was previously," Sabet created.
In addition toso that the review of applications for the previous selection, the HapMap data give scientists a new way to identify new candidates for natural selection.
The objective
Successful completion of the HapMap has not only the completion of the human genome in 2001, but also in the massive effort to characterize its roots and catalog millions of SNPs across the genome.
Based on these initial data, the haplotype structure of the human personGenome was detected in 2001 and leads to the formation of the International HapMap Consortium. Finally, to determine the influence of natural selection in the human genome methods have been described in 2003.
Altshuler, Lander, Gabriel, Daly and many other Broad Institute has led or contributed significantly to these efforts, in addition to their role in the realization of the HapMap and demonstrations of its utility as described above.
InOctober 2002, the International HapMap Consortium set the ambitious goal to create the HapMap, within three years. The Nature paper marks the attainment of this goal with its detailed description of the Phase I HapMap, consisting of more than 1 million SNPs.
The consortium is also nearing completion of Phase II HapMap that will contain nearly three times more SNPs than the original version, allowing researchers to focus their gene searches even more precisely to specificRegions of the genome.
In line with the Broad Institute's commitment to building critical resources for the scientific community, HapMap data are freely available in several public databases, including HapMap Data Coordination Center (http://www.hapmap.org) NIH-funded National Center for Biotechnology Information dbSNP (http://www.ncbi.nlm.nih.gov/SNP/index.html) and the JSNP database (http://snp.ims.u-tokyo.ac. jp) in Japan.
Copyright 2005 Daily News Central
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