Unit of Animal Genomics, GIGA-R, 11 Avenue de l'Hôpital (B34), University of Liège, 4000, Liège, Belgium.
Animal Genomics, ETH Zürich, Universitätstrasse 2, 8092, Zürich, Switzerland.
BMC Genomics. 2022 Feb 10;23(1):114. doi: 10.1186/s12864-022-08328-8.
Meiotic recombination plays an important role in reproduction and evolution. The individual global recombination rate (GRR), measured as the number of crossovers (CO) per gametes, is a complex trait that has been shown to be heritable. The sex chromosomes play an important role in reproduction and fertility related traits. Therefore, variants present on the X-chromosome might have a high contribution to the genetic variation of GRR that is related to meiosis and to reproduction.
We herein used genotyping data from 58,474 New Zealand dairy cattle to estimate the contribution of the X-chromosome to male and female GRR levels. Based on the pedigree-based relationships, we first estimated that the X-chromosome accounted for 30% of the total additive genetic variance for male GRR. This percentage was equal to 19.9% when the estimation relied on a SNP-BLUP approach assuming each SNP has a small contribution. We then carried out a haplotype-based association study to map X-linked QTL, and subsequently fine-mapped the identified QTL with imputed sequence variants. With this approach we identified three QTL with large effect accounting for 7.7% of the additive genetic variance of male GRR. The associated effects were equal to + 0.79, - 1.16 and + 1.18 CO for the alternate alleles. In females, the estimated contribution of the X-chromosome to GRR was null and no significant association with X-linked loci was found. Interestingly, two of the male GRR QTL were associated with candidate genes preferentially expressed in testis, in agreement with a male-specific effect. Finally, the most significant QTL was associated with PPP4R3C, further supporting the important role of protein phosphatase in double-strand break repair by homologous recombination.
Our study illustrates the important role the X-chromosome can have on traits such as individual recombination rate, associated with testis in males. We also show that contribution of the X-chromosome to such a trait might be sex dependent.
减数分裂重组在繁殖和进化中起着重要作用。个体整体重组率（GRR），以每配子的交叉数（CO）来衡量，是一个复杂的特征，已经证明具有遗传性。性染色体在繁殖和与繁殖相关的特征中起着重要作用。因此，X 染色体上存在的变异可能对与减数分裂和繁殖有关的 GRR 遗传变异有很高的贡献。
我们在此使用来自 58474 头新西兰奶牛的基因分型数据来估计 X 染色体对雄性和雌性 GRR 水平的贡献。基于系谱关系，我们首先估计 X 染色体占雄性 GRR 总加性遗传方差的 30%。当依赖 SNP-BLUP 方法进行估计，假设每个 SNP 有小的贡献时，这个百分比等于 19.9%。然后，我们进行了基于单倍型的关联研究来映射 X 连锁 QTL，随后使用推断的序列变体对鉴定的 QTL 进行精细映射。通过这种方法，我们鉴定了三个具有大效应的 QTL，占雄性 GRR 加性遗传方差的 7.7%。交替等位基因的相关效应分别为 +0.79、-1.16 和 +1.18 CO。在雌性中，X 染色体对 GRR 的估计贡献为零，并且没有发现与 X 连锁基因座的显著关联。有趣的是，两个雄性 GRR QTL 与在睾丸中优先表达的候选基因相关，这与雄性特异性效应一致。最后，最显著的 QTL 与 PPP4R3C 相关，进一步支持了蛋白磷酸酶在同源重组修复双链断裂中的重要作用。
我们的研究说明了 X 染色体在与睾丸相关的个体重组率等特征中可能具有重要作用。我们还表明，X 染色体对这种特征的贡献可能与性别有关。
