Candidate lethal haplotypes and causal mutations in Angus cattle.
Candidate lethal haplotypes and causal mutations in Angus cattle.
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DOI：
10.1186/s12864-017-4196-2
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发表时间：
2017-10-18
期刊：
影响因子：
4.4
通讯作者：
Taylor JF
中科院分区：
文献类型：
--
作者：
Hoff JL;Decker JE;Schnabel RD;Taylor JF
如果不加以管理，牲畜群体中近亲繁殖的高比率会对它们的生殖健康产生不利影响。在肉牛中，历史选择策略增加了几个分离的致命常染色体隐性多态性的频率。选择性育种也降低了全基因组单倍型多样性的程度。通过鉴定未观察到纯合子但基于其频率预期纯合子的单倍型，可以定位发育致死隐性基因座的候选者。这种分析不需要观察损失相关的表型（例如，植入失败、妊娠早期流产、出生时畸形）。在这项研究中，使用findhap v2使用52，545个SNP位点估计了3961个注册的安格斯个体的单倍型，该方法利用了该群体中个体之间的复杂谱系。7个位点被检测到拥有单倍型，没有观察到纯合子的形式，尽管有足够高的频率和基于家系的纯合子发生的期望。这些单倍型被鉴定为具有常染色体隐性致死等位基因的候选者。在基因分型的个体中，109个被重新测序到平均27 X的覆盖深度，以识别全基因组范围内推定的功能丧失等位基因，并使用定制的内部开发的管道调用变体。对于这些公牛中存在的候选致死性单倍型，使用称为基因型的序列来鉴定一致的变体。此外，使用109只重新测序的动物对3961只基因分型动物进行变异的全基因组序列插补，以鉴定7个基因座的候选致死隐性变异。插补后，未发现与基于标记的双倍型完全一致的变体。选择性育种程序可以利用与SNP基因型相关的预测致死单倍型。用于鉴定这些单倍型背后的致病变体的测序和其他方法可以允许更有效的管理方法，例如基因编辑。这两种方法将减少近亲繁殖对生育力的负面影响，并最大限度地提高整体遗传收益。
If unmanaged, high rates of inbreeding in livestock populations adversely impact their reproductive fitness. In beef cattle, historical selection strategies have increased the frequency of several segregating fatal autosomal recessive polymorphisms. Selective breeding has also decreased the extent of haplotypic diversity genome-wide. By identifying haplotypes for which homozygotes are not observed but would be expected based on their frequency, candidates for developmentally lethal recessive loci can be localized. This analysis comes without the need for observation of the loss-associated phenotype (e.g., failure to implant, first trimester abortion, deformity at birth). In this study, haplotypes were estimated for 3961 registered Angus individuals using 52,545 SNP loci using findhap v2, which exploited the complex pedigree among the individuals in this population. Seven loci were detected to possess haplotypes that were not observed in homozygous form despite a sufficiently high frequency and pedigree-based expectation of homozygote occurrence. These haplotypes were identified as candidates for harboring autosomal recessive lethal alleles. Of the genotyped individuals, 109 were resequenced to an average 27X depth of coverage to identify putative loss-of-function alleles genome-wide and had variants called using a custom in-house developed pipeline. For the candidate lethal-harboring haplotypes present in these bulls, sequence-called genotypes were used to identify concordant variants. In addition, whole-genome sequence imputation of variants was performed into the set of 3961 genotyped animals using the 109 resequenced animals to identify candidate lethal recessive variants at the seven loci. Following the imputation, no variants were identified that were fully concordant with the marker-based diplotypes. Selective breeding programs could utilize the predicted lethal haplotypes associated with SNP genotypes. Sequencing and other methods for identifying the causal variants underlying these haplotypes can allow for more efficient methods of management such as gene editing. These two methods in total will reduce the negative impacts of inbreeding on fertility and maximize overall genetic gains.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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通讯作者：
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