The major objective of Project 3 is to localize and identify the genes underlying previously detected QTLs forobesity-related phenotypes in the San Antonio Family Heart Study (SAFHS) which contribute to variation inrisk of cardiovascular disease (CVD). This work is based upon large extended Mexican American familiesascertained without regard to disease status. This sample represents -1400 family members which havebeen genotyped for >400 short tandem repeat markers in an 8 centimorgan map and for which genome-widelinkage analysis has been performed for a variety of phenotypes associated with obesity and which arerecognized risk factors for CVD. In this project we will make use of recent advancements in high-throughputSNP typing and sequencing to saturate our areas of interest to further refine the region and help selectpositional candidate genes based on association implemented in a novel Bayesian quantitative traitnucleotide (BQTN) analysis designed to make use of complex family data sets. The identification andselection of these positional candidate genes will be further refined based on the application of an objectivebioinformatics search routine along with insights provided by evidence of strong cis regulation of genes in thespecific regions of interest identified from our unique whole genome transcript data for this population. Oncestrong positional candidate genes have been identified within our regions of interest, they will beresequenced within the set of founders for this sample to identify all common polymorphisms.Characterization of these polymorphisms will permit the remaining individuals to be genotyped and BQTNanalysis will again be employed to identify the presence of potential functional variants in these positionalcandidate genes. When significant evidence of potential functional variants has been detected thesepolymorphisms will be typed in two additional family samples of Mexican Americans in order to look forreplication.
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