Mapping of X-linked Becker muscular dystrophy through crossovers identified by DNA polymorphisms and by haplotype characterization in somatic cell hybrids

Abstract

The analysis of 10 X-linked DNA polymorphisms (five mapping on the short arm and five on the long arm) in two Becker muscular dystrophy pedigrees has been used to localize this gene in the known sequence of DNA polymorphic markers on the X chromosome. In the first pedigree, the carrier mother, whose phase for Becker and for five informative polymorphisms is known, has transmitted a double recombinant X chromosome to one of her two affected sons. The discordance between these two affected brothers for four of the five informative polymorphisms indicates that the Becker gene is located between RC8 or D2 on one side and pDP34 on the other. In the second pedigree, where the maternal grandfather is dead and two maternal first cousins are affected, the phase of DNA polymorphic alleles has been identified in somatic cell hybrids resulting from the fusion of hamster fibroblasts with lymphocytes of the mothers and aunt of the patients. The discordance between the two first cousins for two of the four informative DNA polymorphisms is best explained by the occurrence of a single recombination in the X chromosome carried by one of them. This result further restricts the localization of the Becker gene to a region of the short arm delimited by B24 and L 1.28. Regional and fine gene mapping through the approach described in this paper should become useful in the future for X-linked as well as for autosomal genes.