Homozygosity mapping of Arachnomelia in Brown cattle"

Fifteen calves affected with arachnomelia were sampled in the Swiss and Italian Brown cattle population. Analysis of the pedigree data confirmed monogenic autosomal recessive inheritance and revealed that all affected individuals traced back to a single acknowledged carrier founder sire. Eight affected offspring and 10 available relatives were genotyped for a panel of 240 microsatellites spanning the 29 bovine autosomes. Homozygosity mapping showed homozygosity of all cases at two adjacent microsatellite markers on BTA5. For fine mapping purposes 14 additional BTA5 microsatellites were genotyped in all available cases and indicated shared homozygous haplotypes across 20 Mb among affected individuals. A second pedigree with 23 acknowledged carriers among 34 sires in total related to the founder were genotyped for these markers. Linkage and haplotype analysis showed that the arachnomelia mutation could be assigned to a 7.2 Mb candidate region (LOD score >6). The linked markers can be used for indirect determination of the arachnomelia genotype in offspring of related carrier sires. This bovine chromosome segment corresponds to an ortholog segment of HSA12q containing more than 140 annotated genes and loci. The only obvious functional candidate gene of this region GDF11 is probably not responsible for this fatal bovine disorder.