This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The CANHR Genetics project (Boyer, project PI) is focused on the identification of genetic, and gene by environment interactions involved in the development of obesity in Yup ik Eskimos. In collaboration with investigators at Columbia University, we have recently obtained preliminary results from a candidate gene study interrogating 384 SNPs in 25 candidate genes. Preliminary association results have identified ten genes that are significantly associated with one or more obesity phenotypes in our Yup ik Eskimo study population. We are currently evaluating gene-gene and pathway interactions to identify biologically plausible pathways and networks of genes that may be implicated in obesity. We have also begun our resequencing effort to gain preliminary data for Dr. Boyer s RO1 re-submission application, and have completed resequencing four candidate genes. We selected 30 unrelated individuals from seven villages for resequencing and identified 57 SNPs, 22 (42%) of these SNPs had not been previously identified. We then analyzed all resequenced SNPs using the multimarker predictor method implemented in the Tagger program (Haploview software), and an r2 threshold of 0.8 revealed that 30 tagging SNPs will capture all of the allelic diversity found in the resequenced regions of our Yup ik samples. Although encouraging results from large-scale tagSNP portability studies have recently been published, the HapMap tagSNPs only pick up only 33% of the common variation found in the Yup ik resequenced regions. Therefore, we conclude that it is very important to resequence our candidate genes in Yup ik Eskimos. Nevertheless, we propose supplementation of our Yup ik SNP set with HapMap tagSNPs to provide higher density coverage of each gene. No changes are expected in the gender/minority composition of this subproject.
Showing the most recent 10 out of 96 publications
