A genetic linkage map of the Syrian hamster and localization of cardiomyopathy locus on chromosome 9qa2.1-b1 using RLGS spot-mapping

The Syrian cardiomyopathic hamster1 (BIO14.6) has an inherited form of progressive myocardial necrosis and congestive heart failure. Although widely studied2–4 as an animal model for human hypertrophic cardiomyopathy, further genetic analysis has been limited by a scarcity of DMA markers. Until now, only six autosomal linkage groups have been described5 and the number of polymorphic loci was extremely limited. In this study, we applied the restriction landmark genome scanning (RLGS) spot-mapping method6–9 to construct a genetic map of the Syrian hamster (Mesocricetus auratus) using 72 back-cross progeny. Although the polymorphic rate is very low (3–7%) between the strains, 531 polymorphic spots/loci were mapped, showing the power of this approach and reasonable applicability to other organisms lacking a well-defined genetic map. Further, the spot markers which flank the cardiomyopathy (cm) locus were cloned to determine the chromosomal location of cm by fluorescent in situ hybridization (FISH) analysis, resulting in the assignment of the locus to the centromeric region of hamster chromosome 9qa2.1–b1. Several candidate genes responsible for hypertrophic cardiomyopathy in humans have been excluded.