Linkage disequilibrium study of RFLPs detected at the human muscle nicotinic acetylcholine receptor subunit genes.

We screened DNA from unrelated individuals for RFLPs in the muscle nicotinic acetylcholine receptor (AcChoR) genes. These RFLP markers can be used for genetic linkage and association studies to test the hypothesis that receptor structure or regulation is involved in the development of myasthenia gravis (MG). The cDNAs from four subunits (alpha, beta, gamma, and delta) of the murine muscle AcChoR were used as probes to identify RFLPs in the homologous human genes. Digestion of DNA from 15 unrelated individuals with a set of 10 restriction enzymes revealed 11 RFLPs. At least one RFLP was found for each subunit gene. Eight RFLPs were found at the linked gamma and delta gene loci, six with minor allele frequencies greater than 15%, making that linkage group a very informative marker locus (PIC = .72). PIC values were calculated for the RFLPs from allele and haplotype frequency estimates obtained from a population sample of 53 individuals. The delta gene was assigned by in situ hybridization to region q31----q34 of chromosome 2. All pairs of RFLPs were analyzed for linkage disequilibrium. Of the 16 pairs of RFLPs from the same gene or from the linked gamma and delta genes, 13 pairs showed evidence of disequilibrium that was significant, with P less than .05. The implications of these results are discussed.