1000 Genomes project: five-year plan exceeded
The second phase of the 1000 Genomes project has been completed. As a result of a five-year study, the genomes of 1,092 representatives of 14 different populations were sequenced and analyzed.
The ultimate goal of this ambitious international project is to provide biologists and medical practitioners with information that will help them understand the normal range of genetic variants that make up the human genome. This, in turn, will make it possible to interpret the information contained in the genome in a broader context.
The analyzed populations were selected based on data on their migration history and genetic relationship with each other. Healthy donors who were not related were randomly selected in each population. Cells were isolated from the collected blood samples, from which cell lines were grown, suitable for endless storage and reproduction. The DNA of the isolated cells was sequenced, and the data obtained were entered into publicly available databases.
After the publication of the sequence of the first sequenced human genome in 2003, it became clear to specialists that, contrary to traditional beliefs, 98.5% of human genetic material does not encode proteins. Currently, scientists know the functions of a number of non-coding regions of the genome, but most of the genetic sequence still remains a mystery.
There are reasons to assume that at least part of the "dark matter" in the genome is responsible for predisposition to various diseases.
The genetic variations identified in the representatives of the analyzed populations were divided into categories depending on the frequency of occurrence. Variants detected in more than 5% of samples were considered common, in 0.5-5% of samples – sparsely distributed, and in less than 0.5% of samples – rare.
The 14 analyzed populations were divided into 4 groups: European, African, East Asian and American origin. As the researchers expected, most of the common variants had already been identified in earlier studies, while the frequency of their occurrence varied little depending on the origin of the group.
On the contrary, 58% of low-prevalence and 87% of rare variants were described for the first time. In some cases, rare variants were found in a particular population twice as often as in a larger group including this population. Different numbers of rare variants were also identified in different populations, the largest variety of which was characteristic of the Spanish, Finnish and African-American populations.
It turned out to be a complete surprise that, with respect to rare variants, healthy study participants were carriers of 130 to 400 variants that change the structure of protein molecules, 10-20 variants that deprive the proteins encoded by them of the ability to perform their inherent functions, 2-5 variants that violate the functions of proteins and 1-2 variants associated with malignant tumors. This means that healthy people, regardless of ethnic origin, are carriers of approximately the same number of rare genetic variants that are dangerous to health.
According to one of the leaders of the study, Professor Aravinda Chakravarti from Johns Hopkins University, there are a number of factors that ensure the survival of people, despite the presence of such a large number of errors in their genomes. One of the mechanisms is that the mutant allele is present only on one chromosome out of a pair, and the second, normal variant of the gene is enough for the body to function normally. Another factor is the presence of "reserve" genes in other regions of the genome, which in some cases can compensate for the consequences of the non-functionality of a particular protein.
The first phase of the 1000 Genomes project was completed in 2008. It was planned as a preliminary study of a part of the genomes sequenced for the second phase, and demonstrated the feasibility of searching for genetic markers of various diseases. As part of the final phase of the project, it is planned to sequence the genomes of another 1,500 people from 11 previously uncovered populations. More than 100 scientists from 111 research institutions around the world have already participated in the project.
Article The 1000 Genomes Project Consortium. An integrated map of genetic variation from 1,092 human genomes is published in open access in the journal Nature.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Newswise:
Scientific Team Sequences 1092 Human Genomes to Determine Standard Range of Human Genetic Variation.
02.11.2012