Genome-wide association study shows that microtia in Altay sheep is caused by a 76 bp duplication of HMX1.

Microtia is a congenital malformation of the external ear that can be observed in many species including sheep. However, the genetic basis of microtia still remains unclear. Here, a GWAS was conducted to investigate the genetic basis underlying microtia. A total of 55 samples from 26 microtia and 29 normal animals were genotyped with Illumina OvineHD BeadChip. The strongest significant SNP was identified on OAR6, approximating the evolutionarily conserved region of the HMX1 gene, which is related to congenital malformations of the external ear in other species such as cattle and rats. Sequencing an evolutionarily conserved region surrounding HMX1 revealed a duplication of 76 bp, which is concordant with microtia, suggesting a dominant inheritance mode. Identification of this causal mutation in the HMX1 gene indicates the role of this particular gene in the development of the external ear and provides a genetic marker for selection against microtia.