To produce a 25 cM base genetic map in Pima Indians, we have genotyped over 150 highly heterozygous short tandem repeat polymorphisms, STRPs, scattered across the genome in a data set of 1000 individuals comprising 250 nuclear families. The average heterozygosity in Pima Indians is approximately 11% lower than the reported average heterozygosity in Caucasians for these STRPs. Linkage analysis using these STRP markers has revealed regions on chromosomes 1,6, and 7 that show linkage to various aspects of carbohydrate or fat metabolism or show linkage to diabetes. We have genotyped additional markers in the regions of linkage, and have started to physical mapping on chromosome 1 with several YACs which include the marker showing linkage. In addition, a region on chromosome 20 showed strong linkage to the quantitative character, stature. Analysis of additional markers supports the original linkage observation. A candidate gene, the bone morphogenetic protein 2 gene, BMP2, lies in this region. We have screened 40 individuals using single stranded conformational polymorphism, SSCP, for structural variation in the BMP2 gene that codes for the mature protein. No consistent changes were observed. Sequence analysis of these individuals suggests a single nucleotide substitution not detected with SSCP.
