The goal of the project is, for the first time, to carry out genome-wide searches:
(a) for differences in integration sites (ISs) between human and other hominoids, and;
(b) for deletion/insertion polymorphisms of Alu, L1 and HERV retroelements (RE) in various human populations from different Russian areas.

Within the framework of these major goals the project anticipates:
1. to determine the sequences of the polymorphic integration sites (PSIs) and human specific integration sites (HSIs) different by the presence/absence of the REs between human and ape genomes;
2. to identify PSIs and HSIs in available human genome sequence data bases;
3. to determine gene contents and corresponding ESTs around the PSIs and HSIs by means of bioinformatic tools, and
4. to investigate frequencies of the alleles corresponding to loci of PSIs and associations of the RE insertion polymorphisms with various diseases in various Russian populations.

The RE insertion polymorphisms offer several advantages over other types of polymorphisms for human evolution and populations studies, as well as for gene mapping: they are stable and rarely undergo deletions, and the presence of an RE represents identity by descent, because the probability that two different REs were independently integrated exactly into the same site is negligible. Moreover, the ancestral state of RE insertion polymorphisms is known to be the absence of the RE. This can be used to root plots/trees of population relationships. Technically, their typing can be readily done by rapid, simple, polymerase chain reaction (PCR)-based assays. Thus the research will provide new convenient polymorphic markers that can be used in future for analyses of relationship between populations, for genetic mapping of the disease genes as well as for better understanding of the human genome evolution.
In the course of the project the HSIs libraries for the Alu Ya5 and Yb8, L1 Ta and HERV-K(HML-2) LTRs will be obtained, and the HSIs and PSIs will be sequenced and mapped. The genes adjacent to HSIs will be identified. In particular, the identification of HSIs in the vicinity of human genes, especially those involved in embryo development, could reveal candidate regulatory elements within REs capable of affecting the genes regulation and via this influencing the split of the human and chimpanzee lineages.
Also one can anticipate interesting results on application of newly discovered insertion polymorphisms to Russian population relationships. The frequencies of alleles corresponding to discovered RE insertion polymorphic loci will be determined for populations inhabiting various Russian regions, and diseases association study with the alleles distribution will be implemented at the population level. This will help to elaborate data on relationships of different ethnic groups. Possibly new candidate genes implicated in complex diseases predisposition will be revealed.
To achieve the goals formulated above a newly developed technique named Targeted Genomic Difference Analysis (TGDA) will be used based on selective amplification of RE flanking regions over the whole genome and subsequent subtractive hybridisation (SH) of the amplicons obtained. Also a new time and cost saving hybridization approach will be developed to detect insertion polymorphisms.
The international team formed to reach the goals of the project involves collaborating groups well trained to carry out these experiments. This is a well-experienced and interdiscipline team. Each member of the team successfully worked before with members of the local team and with the international partners.
The results obtained will be published jointly in peer-reviewed international journals, and reports to International Scientific Meetings will be presented. All techniques developed, materials and information concerning useful markers obtained during the project implementation will be freely available to the scientific community through e-mail and Internet communications.