Genome-wide association and genomic prediction for a reproductive index summarizing fertility outcomes in U.S. Holsteins

Subfertility represents one major challenge to enhancing dairy production
and efficiency. Herein, we use a reproductive index (RI) expressing the
predicted probability of pregnancy following artificial insemination with
Illumina 778K genotypes to perform single and multi-locus genome-wide
association analyses (GWAA) on 2,448 geographically diverse U.S. Holstein
cows and produce genomic heritability estimates. Moreover, we use genomic
best linear unbiased prediction (GBLUP) to investigate the potential
utility of the RI by performing genomic predictions with cross-validation.
Notably, genomic heritability estimates for the U.S. Holstein RI were
moderate ( 0.1654± 0.0317 – 0.2550 ± 0.0348), while single and multi-locus
GWAA revealed overlapping quantitative trait loci (QTL) on BTA6 and BTA29,
including known QTL for daughter pregnancy rate (DPR) and cow conception
rate (CCR). Multi-locus GWAA revealed seven additional QTL, including one
on BTA7 (60 Mb) which is adjacent to a known heifer conception rate (HCR)
QTL (59 Mb). Positional candidate genes for the detected QTL included male
and female fertility loci (i.e., spermatogenesis, oogenesis), meiotic and
mitotic regulators, and genes associated with immune response, milk yield,
enhanced pregnancy rates, and the reproductive-longevity pathway.
 Based on the proportion of phenotypic variance explained (PVE),
all detected QTL (n = 13; P ≤ 5e-05) were estimated to have moderate (1.0%
< PVE ≤ 2.0%) or small effects (PVE ≤ 1.0%) on the predicted
probability of pregnancy.  Genomic prediction using GBLUP with
cross-validation (k = 3) produced mean predictive abilities
(0.1692–0.2301) and mean genomic prediction accuracies (0.4119–0.4557)
that were similar to bovine health and production traits previously
investigated.

生育力低下是制约奶牛养殖生产效率提升的一大核心挑战。本研究采用繁殖指数（RI）——该指数可表征荷斯坦奶牛经人工授精后妊娠的预测概率——以Illumina 778K基因分型芯片对2448头地理分布广泛的美国荷斯坦奶牛开展单基因座与多基因座全基因组关联分析（GWAA），并估算基因组遗传力。此外，本研究借助基因组最佳线性无偏预测（GBLUP），通过交叉验证开展基因组预测，以探究繁殖指数的应用潜力。值得注意的是，美国荷斯坦奶牛繁殖指数的基因组遗传力估算值处于中等水平（0.1654±0.0317 ~ 0.2550±0.0348）；单基因座与多基因座GWAA均在牛6号染色体（BTA6）与牛29号染色体（BTA29）上发现了重叠的数量性状位点（QTL），其中包含已知的与女儿妊娠率（DPR）和母牛受胎率（CCR）相关的QTL。多基因座GWAA还额外发现了7个QTL，其中位于牛7号染色体（BTA7）60 Mb处的位点毗邻已知的青年母牛受胎率（HCR）QTL（59 Mb）。本研究鉴定到的QTL的位置候选基因涵盖雌雄生育相关位点（如精子发生、卵子发生相关基因）、减数分裂与有丝分裂调控因子，以及与免疫应答、产奶量、妊娠率提升及生殖长寿通路相关的基因。基于表型变异解释率（PVE）估算，所有鉴定到的13个QTL（P≤5e-05）对妊娠预测概率的效应均为中等（1.0% < PVE ≤2.0%）或微弱（PVE ≤1.0%）。采用GBLUP结合3折交叉验证（k=3）开展的基因组预测结果显示，平均预测能力为0.1692~0.2301，平均基因组预测准确度为0.4119~0.4557，这一结果与此前已报道的牛健康与生产性状的预测结果相当。