Juxtaposed short sequence repeat types and haplotypes near exon 3 of the insulin receptor locus among Mexican Americans

Abstract The insulin receptor has been sequenced on numerous occasions and reports suggest several potential polymorphisms, as do a number of reports of single base changes. Examining these reports identifies five potential polymorphisms at or near exon 3. Three of these—codon 233 (CTG to CCG), codon 234 (GAC to GAT), and codon 276 (CAG to CAA)—predict restriction site differences. Just 5′ of exon 3, the sequence suggests the presence of two short sequence repeats (SSRs), one with ATTT repeats and one with TC dinucleotide repeats. Amplification of exon 3 using the polymerase chain reaction followed by appropriate restriction digestion demonstrated no variation in a sample of 50 Mexican Americans. The codon 276 results were surprising given several reports showing the putative differences. An additional 91 mixed samples were examined and no variation was detected, suggesting that the reported differences likely resulted from sequencing artifacts. Amplification of a smaller fragment demonstrated 10 phenotypes and 7 alleles for the SSR region. Digestion with Mnl I permitted scoring each motif separately and when coupled with the uncut results permits unequivocal classification of haplotypes without familial data. These juxtaposed SSRs should be useful for linkage analysis and investigations of gene structure and evolution.