Haplotypes responsible for early embryonic lethality detected in Nordic Holsteins

Widespread use of a limited number of elite sires in dairy cattle breeding increases the risk of some deleterious allelic variants spreading in the population. Genomic data are being used to detect relatively common (frequency >1%) haplotypes that never occur in the homozygous state in live animals. Such haplotypes likely include recessive lethal or semilethal alleles. The aim of this study was to detect such haplotypes in the Nordic Holstein population and to identify causal genetic factors underlying these haplotypes. Illumina BovineSNP50 BeadChip (Illumina Inc., San Diego, CA) genotypes for 26,312 Nordic Holstein animals were phased to construct haplotypes. Haplotypes that are common in the population but never observed as homozygous were identified. Two such haplotypes overlapped with previously identified recessive lethal mutations in Holsteins—namely, structural maintenance of chromosomes 2 (HH3) and brachyspina. In addition, we identified 9 novel putative recessive lethal-carrying haplotypes, with 26 to 36 homozygous individuals expected among the genotyped animals but only 0 to 3 homozygotes observed. For 2 out of 9 homozygous-deficient haplotypes, insemination records of at-risk mating (carrier bull with daughter of carrier sire) showed reduced insemination success compared with not-at-risk mating (noncarrier bull with daughter of noncarrier sire), supporting early embryonic mortality. To detect the causative variant underlying each homozygous-deficient haplotype, data from the 1000 Bull Genome Project were used. However, no variants or deletions identified in the chromosome regions covered by the haplotypes showed concordance with haplotype carrier status. The carrier status of detected haplotypes could be used to select bulls to reduce the frequency of the latent lethal mutations in the population. If desired, at-risk matings could be avoided.