Wageningen University & Research, Animal Breeding and Genomics, Wageningen, The Netherlands.
Topigs Norsvin Research Center, Beuningen, the Netherlands.
BMC Genomics. 2017 Nov 9;18(1):858. doi: 10.1186/s12864-017-4278-1.
Lethal recessive variation can cause prenatal death of homozygous offspring. Although usually present at low-frequency in populations, the impact on individual fitness can be substantial. Until recently, the presence of recessive embryonic lethal variation could only be measured indirectly through reduced fertility. In this study, we estimate the presence of genetic loci associated with both early and late termination of development during gestation in pigs from the wealth of genome data routinely generated by a commercial breeding company.
We examined three commercial pig (Sus scrofa) populations for potentially deleterious genetic variation based on 80 K SNP-chip genotypes, and estimate the effects on reproductive traits. 24,000 pigs from three populations were analyzed for missing or depletion of homozygous haplotypes. We identified 145 haplotypes (ranging from 0.5-4 Mb in size) in the genome with complete absence or depletion of homozygous animals. Thirty-five haplotypes show a negative effect on at least one of the analysed reproductive traits (total number born, number of stillborn, and number of mummified piglets). One variant in particular appeared to result in relative late termination of development of fetuses, responsible for a significant fraction of observed stillborn piglets ('mummies'), as they die mid-gestation. Moreover, we identified the BMPER gene as a likely candidate underlying this phenomenon.
Our study shows that although lethal recessive variation is present, the frequency of these alleles is invariably low in these highly managed populations. Nevertheless, due to cumulative effects of deleterious variants, large numbers of affected offspring are produced. Furthermore, our study demonstrates the use of a large-scale commercial genetic experiment to systematically screen for 'natural knockouts' that can increase understanding of gene function.
致死性隐性变异可导致纯合子后代的产前死亡。尽管在人群中通常以低频率存在，但对个体适应性的影响可能是巨大的。直到最近，隐性胚胎致死变异的存在只能通过降低生育率来间接测量。在这项研究中，我们利用商业育种公司常规产生的大量基因组数据，估计了与猪在妊娠期早期和晚期发育终止相关的遗传基因座的存在。
我们基于 80K SNP 芯片基因型，对三个商业猪（Sus scrofa）群体进行了潜在有害遗传变异的研究，并估计了它们对繁殖性状的影响。我们对来自三个群体的 24000 头猪进行了缺失或纯合子缺失的分析。我们在基因组中确定了 145 个大小在 0.5-4 Mb 之间的单倍型，这些单倍型完全不存在或缺失纯合动物。35 个单倍型对至少一个分析的繁殖性状（总产仔数、死产数和木乃伊仔猪数）有负面影响。一个特别的变异似乎导致了胎儿发育的相对晚期终止，导致了大量观察到的死产仔猪（木乃伊），因为它们在妊娠中期死亡。此外，我们确定了 BMPER 基因可能是这一现象的候选基因。
我们的研究表明，尽管存在致死性隐性变异，但在这些高度管理的群体中，这些等位基因的频率始终很低。然而，由于有害变异的累积效应，大量受影响的后代被产生。此外，我们的研究表明，利用大规模商业遗传实验可以系统地筛选“自然敲除”，从而增加对基因功能的理解。
