GenPhySE, Université de Toulouse, INRAE, ENVT, 31326, Castanet-Tolosan, France.
Allice, 149 rue de Bercy, 75595, Paris, France.
Genet Sel Evol. 2021 May 1;53(1):41. doi: 10.1186/s12711-021-00634-1.
Homozygous recessive deleterious mutations can cause embryo/fetal or neonatal lethality, or genetic defects that affect female fertility and animal welfare. In livestock populations under selection, the frequency of such lethal mutations may increase due to inbreeding, genetic drift, and/or the positive pleiotropic effects of heterozygous carriers on selected traits.
By scanning the genome of 19,102 Lacaune sheep using 50 k single nucleotide polymorphism (SNP) phased genotypes and pedigree data, we identified 11 Lacaune deficient homozygous haplotypes (LDHH1 to LDHH11) showing a highly significant deficit of homozygous animals ranging from 79 to 100%. These haplotypes located on chromosomes 3, 4, 13, 17 and 18, spanned regions from 1.2 to 3.0 Mb long with a frequency of heterozygous carriers between 3.7 and 12.1%. When we compared at-risk matings (between carrier rams and daughters of carrier rams) and safe matings, seven of the 11 haplotypes were associated with a significant alteration of two fertility traits, a reduced success of artificial insemination (LDHH1, 2, 8 and 9), and/or an increased stillbirth rate (LDHH3, 6, 8, 9, and 10). The 11 haplotypes were also tested for a putative selective advantage of heterozygous carrier rams based on their daughter yield deviation for six dairy traits (milk, fat and protein yields, fat and protein contents and lactation somatic cell score). LDHH1, 3, 4, 5, 7, 9 and 11 were associated with positive effects on at least one selected dairy trait, in particular milk yield. For each haplotype, the most probable candidate genes were identified based on their roles in lethality of mouse knock-out models and in mammalian genetic disorders.
Based on a reverse genetic strategy, we identified at least 11 haplotypes with homozygous deficiency segregating in French Lacaune dairy sheep. This strategy represents a first tool to limit at-risk matings in the Lacaune dairy selection scheme. We assume that most of the identified LDHH are in strong linkage disequilibrium with a recessive lethal mutation that affects embryonic or juvenile survival in sheep but is yet to be identified.
纯合隐性有害突变可导致胚胎/胎儿或新生儿致死，或导致影响雌性生育能力和动物福利的遗传缺陷。在受选择的家畜群体中，由于近交、遗传漂变和/或杂合携带者对选择性状的正多效性影响，此类致死突变的频率可能会增加。
通过使用 50k 单核苷酸多态性（SNP）相位基因型和系谱数据扫描 19102 只拉卡奴绵羊的基因组，我们鉴定了 11 个拉卡奴绵羊纯合缺失单倍型（LDHH1 至 LDHH11），这些单倍型显示出高度显著的纯合动物缺陷，范围从 79%到 100%。这些单倍型位于染色体 3、4、13、17 和 18 上，跨越 1.2 到 3.0 Mb 长的区域，杂合携带者的频率在 3.7%到 12.1%之间。当我们比较风险交配（携带公羊与携带公羊的女儿之间的交配）和安全交配时，这 11 个单倍型中的 7 个与两个生育力性状的显著改变相关，即人工授精成功率降低（LDHH1、2、8 和 9）和/或死产率增加（LDHH3、6、8、9 和 10）。还基于杂合携带公羊对六个乳用性状（牛奶、脂肪和蛋白质产量、脂肪和蛋白质含量以及泌乳体细胞评分）的女儿产量偏差，对这 11 个单倍型进行了潜在选择优势的测试。LDHH1、3、4、5、7、9 和 11 与至少一个选择的乳用性状呈正相关，特别是产奶量。对于每个单倍型，根据其在小鼠敲除模型的致死性和哺乳动物遗传疾病中的作用，确定了最可能的候选基因。
基于反向遗传策略，我们在法国拉卡奴奶绵羊中鉴定了至少 11 个纯合缺失的单倍型。该策略代表了限制拉卡奴奶绵羊选择计划中风险交配的第一个工具。我们假设，大多数鉴定的 LDHH 与影响绵羊胚胎或幼体存活的隐性致死突变密切相关，但尚未确定该突变。
