Haplotypes that are common in a population but not observed as homotypes in living animals may harbor lethal alleles that compromise embryo survival. In this study, we searched for homozygous-deficient haplotypes in the genomes of 19,309 Nordic Red Dairy (RDC) and 4,291 Danish Jersey (JER) cattle genotyped using the Illumina BovineSNP50 BeadChip (Illumina Inc., San Diego, CA). For statistically significant deficient haplotypes, we evaluated the effect on nonreturn rate in at-risk matings (mating between carrier bull and daughter of carrier sire) versus not-at-risk matings (mating between noncarrier bull and daughter of noncarrier sire). Next, we analyzed whole-genome sequence variants from the 1000 Bull Genomes Project to identify putative causal variants underlying these haplotypes. In RDC, we identified 3 homozygous-deficient regions (HDR) that overlapped with known recessive lethal mutations: a 662-kb deletion on chromosome 12 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 15 novel HDR and their tag haplotypes for the underlying causative variants. The tag haplotype located between 39.2 and 40.3 Mbp on chromosome 18 had a negative effect on nonreturn rate in at-risk mating, confirming embryonic lethality. In Danish Jersey, we identified 12 novel HDR and their tag haplotypes for underlying causative variants. For 3 of these 12 tag haplotypes, insemination records of at-risk mating showed a negative effect on nonreturn rate, confirming the association with early embryonic mortality. Cattle that had both genotype and whole-genome sequence data were analyzed to detect the causative variants underlying each tag haplotype. However, none of the functional variants or deletions showed concordance with carrier status of the novel tag haplotypes. Carrier status of these detected haplotypes can be used to select bulls to reduce the frequencies of lethal alleles in the population and to avoid at-risk matings.

中文翻译：

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新颖的单倍型负责北欧红和丹麦泽西岛牛的产前死亡。

在种群中很常见但未在活动动物中观察到的单倍型的单倍型可能会包含致命的等位基因，从而损害胚胎的存活。在这项研究中，我们在使用Illumina BovineSNP50 BeadChip（Illumina Inc.，San Diego，CA）进行基因分型的19,309头北欧红奶牛（RDC）和4,291头丹麦泽西（JER）牛的基因组中搜索了纯合缺陷型单倍型。对于统计学上显着的单倍型缺陷，我们评估了高风险交配（carrier公牛和of公子之间的交配）和非高风险交配（非carrier公牛和非carrier公子之间的交配）对单向率的影响。接下来，我们分析了1000 Bull Bullomes Project的全基因组序列变体，以确定这些单倍型的潜在因果变体。在RDC中，我们确定了3个与已知隐性致命突变重叠的纯合缺陷区（HDR）：RDC [在线孟德尔动物遗传学（OMIA）001901-9913）12号染色体上的662-kb缺失，TUBD1，g中的错义突变。 11063520T> C，位于Braunvieh牛中（OMIA 001939-9913），而RDC中23号染色体上有525-kb缺失（OMIA 001991-9913）]。此外，我们确定了15种新颖的HDR及其潜在潜在变异的标签单倍型。位于18号染色体上39.2至40.3 Mbp之间的标签单倍型对高风险交配中的单向返回率具有负面影响，证实了胚胎的致死性。在丹麦泽西岛，我们确定了12种新颖的HDR及其潜在潜在变异体的标签单倍型。对于这12种标签单倍型中的3种，高风险交配的授精记录显示了对单归率的负面影响，证实与早期胚胎死亡率的关联。分析了具有基因型和全基因组序列数据的牛，以检测每种标签单倍型的致病变异。然而，功能变体或缺失均未显示出与新型标签单倍型的携带者状态一致。这些检测到的单倍型的携带者状态可用于选择公牛，以降低种群中致死等位基因的频率并避免高风险交配。