Bayesian Inference Identifies a Candidate Region Associated with Canine Cryptorchidism that Includes the AMHR2 Gene

Cryptorchidism is a condition whereby one or both testes fail to descend into the scrotal sac.  It is a common congenital disorder prevalent in many mammalian species.  Cryptorchidism is considered to be caused by the interaction of genetic, epigenetic and environmental factors.  No single mutated gene has been found to cause more than 10% of cryptorchids.  Here we performed a genome wide association study (GWAS) using case-control analysis in PLINK software and the BayesB approach in GenSel software with a 1Mb window of SNPs or haplotypes.  The haplotypes were constructed from a genealogical tree on the population of 204 Siberian Huskies and its 3 subgroups clustered by genomic relationships to account for population structure.  No significant association was observed in the case-control analyses after FDR corrections in PLINK.  In contrast, the BayesB analyses identified a 1Mb region on dog chromosome 27 (CFA27) containing the AMHR2 (anti-mullenrian hormone type II receptor) gene that explained a high percentage of genetic variance in subgroup 1 (~ 10 fold greater than the expected value for an infinitesimal model in the SNP window analysis and ~ 9 fold greater in the haplotype window analysis).  It is known that mutations in AMHR2 cause persistent mullerian duct syndrome (PMDS) in humans and the majority of such patients with PMDS exhibit cryptorchidism.  In conclusion, we identified a putative candidate region at the 4^th Mb on CFA27 (CanFam2.0) harboring a very promising functional candidate gene AMHR2 associated with the development of cryptorchidism in our Siberian Husky population.