Mapping a Gene for Familial Hypertrophic Cardiomyopathy to Chromosome 14q1

TLDR

The study aimed to locate the chromosomal position of the gene causing familial hypertrophic cardiomyopathy in a large kindred using clinical and molecular genetic methods. Linkage analysis of polymorphic DNA markers across the genome was performed on 20 affected and 24 deceased family members, with lod scores calculated to assess co‑inheritance with the disease. A locus, D14S26 on chromosome 14q1, co‑inherited with the disease with a lod score of +9.37, indicating odds greater than 2,000,000,000 to 1 that the pathogenic gene resides on chromosome 14q1. Published in N Engl J Med 1989, 321:1372–8.

Abstract

To identify the chromosomal location of a gene responsible for familial hypertrophic cardiomyopathy, we used clinical and molecular genetic techniques to evaluate the members of a large kindred. Twenty surviving and 24 deceased family members had hypertrophic cardiomyopathy; 58 surviving members were unaffected. Genetic-linkage analyses were performed with polymorphic DNA loci dispersed throughout the entire genome, to identify a locus that was inherited with hypertrophic cardiomyopathy in family members. The significance of the linkage detected between the disease locus and polymorphic loci was assessed by calculating a lod score (the logarithm of the probability of observing coinheritance of two loci, assuming that they are genetically linked, divided by the probability of detecting coinheritance if they are unlinked). A DNA locus (D14S26), previously mapped to chromosome 14 and of unknown function, was found to be coinherited with the disease in this family. No instances of recombination were observed between the locus for familial hypertrophic cardiomyopathy and D14S26, yielding a lod score of +9.37 (θ= 0). These data indicate that in this kindred, the odds are greater than 2,000,000,000:1 that the gene responsible for familial hypertrophic cardiomyopathy is located on chromosome 14 (band q1). (N Engl J Med 1989; 321:1372–8.)