Deficiency in homozygous haplotypes reveals recessive lethal variants affecting fertility and viability in the Friesian horse.

backgroundRecessive lethal alleles causing pre- or postnatal death in homozygous mutant animals, could lead to reduced fertility success. The Friesian horse breed has signs of reduced fertility and has faced high inbreeding rates in the past (∆F > 1%). Consequently, by genetic drift lethal alleles may have reached moderate to high frequencies in the population. Our aim was to identify lethal recessive alleles that — when homozygous — may cause pre- or postnatal death in the Friesian horse.

resultsWe analyzed genotypes (70 K SNP) of over 8,000 Friesian horses, looking for haplotypes with a homozygous deficiency, and used available sequence data of 50 Friesian sires to pinpoint the likely causal variant. A deficit in homozygous animals suggests a lethal allele, because individuals inheriting two copies of such an allele likely die before birth or die before being genotyped, creating a detectable imbalance in genotype frequencies. We found ten candidate haplotypes in the Friesian horse with carrier frequencies ranging from 8.0 to 22.1%. We identified candidate causal variants of six haplotypes, of which two were associated with the already known genetic disorders dwarfism and hydrocephalus. The other candidate variants were a 261-kilobase-pair deletion affecting several non-coding RNA’s, and a 14-base-pair frameshift deletion in the MET gene. Three haplotypes in LD comprised the deletion in MET and were associated with a 25% reduction (P < 0.001) in insemination success in risk matings, likely caused by early embryonic lethality.

conclusionsIn general, considering the population characteristics of domestic horse breeds, we strongly recommend performing such analyses in other horse breeds using the increasingly available genotype data. Such analyses could provide important contribution to the improvement of fertility rates in horse populations.