Novel haplotypes responsible for prenatal death in Nordic Red and Danish Jersey cattle

摘要

Haplotypes that are common in a population but notobserved as homotypes in living animals may harborlethal alleles that compromise embryo survival. In thisstudy, we searched for homozygous-deficient haplotypesin the genomes of 19,309 Nordic Red Dairy (RDC)and 4,291 Danish Jersey (JER) cattle genotyped usingthe Illumina BovineSNP50 BeadChip (Illumina Inc.,San Diego, CA). For statistically significant deficienthaplotypes, we evaluated the effect on nonreturn ratein at-risk matings (mating between carrier bull anddaughter of carrier sire) versus not-at-risk matings(mating between noncarrier bull and daughter of noncarriersire). Next, we analyzed whole-genome sequencevariants from the 1000 Bull Genomes Project to identifyputative causal variants underlying these haplotypes.In RDC, we identified 3 homozygous-deficientregions (HDR) that overlapped with known recessivelethal mutations: a 662-kb deletion on chromosome12 in RDC [Online Mendelian Inheritance in Animals(OMIA) 001901-9913), a missense mutation in TUBD1,g.11063520T>C, in Braunvieh cattle (OMIA 001939-9913), and a 525-kb deletion on chromosome 23 in RDC(OMIA 001991-9913)]. In addition, we identified 15novel HDR and their tag haplotypes for the underlyingcausative variants. The tag haplotype located between39.2 and 40.3 Mbp on chromosome 18 had a negativeeffect on nonreturn rate in at-risk mating, confirmingembryonic lethality. In Danish Jersey, we identified 12novel HDR and their tag haplotypes for underlyingcausative variants. For 3 of these 12 tag haplotypes,insemination records of at-risk mating showed a negativeeffect on nonreturn rate, confirming the associationwith early embryonic mortality. Cattle that hadboth genotype and whole-genome sequence data wereanalyzed to detect the causative variants underlyingeach tag haplotype. However, none of the functionalvariants or deletions showed concordance with carrierstatus of the novel tag haplotypes. Carrier status ofthese detected haplotypes can be used to select bulls toreduce the frequencies of lethal alleles in the populationand to avoid at-risk matings.