Centre for Integrative Genetics (CIGENE), Department of Animal and Aquacultural Sciences (IHA), Norwegian University of Life Sciences (UMB), PO Box 5003, N-1432 Ås, Norway.
BMC Genet. 2013 Jan 2;14:1. doi: 10.1186/1471-2156-14-1.
A genome wide association study for litter size in Norwegian White Sheep (NWS) was conducted using the recently developed ovine 50K SNP chip from Illumina. After genotyping 378 progeny tested artificial insemination (AI) rams, a GWAS analysis was performed on estimated breeding values (EBVs) for litter size.
A QTL-region was identified on sheep chromosome 5, close to the growth differentiation factor 9 (GDF9), which is known to be a strong candidate gene for increased ovulation rate/litter size. Sequencing of the GDF9 coding region in the most extreme sires (high and low BLUP values) revealed a single nucleotide polymorphism (c.1111G>A), responsible for a Val→Met substitution at position 371 (V371M). This polymorphism has previously been identified in Belclare and Cambridge sheep, but was not found to be associated with fertility. In our NWS-population the c.1111G>A SNP showed stronger association with litter size than any other single SNP on the Illumina 50K ovine SNP chip. Based on the estimated breeding values, daughters of AI rams homozygous for c.1111A will produce minimum 0.46 - 0.57 additional lambs compared to daughters of wild-type rams.
We have identified a missense mutation in the bioactive part of the GDF9 protein that shows strong association with litter size in NWS. Based on the NWS breeding history and the marked increase in the c.1111A allele frequency in the AI ram population since 1983, we hypothesize that c.1111A allele originate from Finnish landrace imported to Norway around 1970. Because of the widespread use of Finnish landrace and the fact that the ewes homozygous for the c.1111A allele are reported to be fertile, we expect the commercial impact of this mutation to be high.
利用 Illumina 公司最近开发的绵羊 50K SNP 芯片，对挪威白绵羊（NWS）的产羔数进行了全基因组关联研究。在对 378 只经过人工授精（AI）测试的后代公羊进行基因分型后，对产羔数的估计育种值（EBV）进行了 GWAS 分析。
在绵羊染色体 5 上，靠近生长分化因子 9（GDF9）的区域被鉴定为一个 QTL 区域，该基因被认为是增加排卵率/产羔数的一个强有力的候选基因。在最极端的公羊（高和低 BLUP 值）的 GDF9 编码区进行测序时，发现了一个单核苷酸多态性（c.1111G>A），导致第 371 位的缬氨酸→蛋氨酸取代（V371M）。该多态性以前在贝尔克拉尔和剑桥绵羊中被发现，但与繁殖力无关。在我们的 NWS 群体中，c.1111G>A SNP 与产羔数的相关性强于 Illumina 50K 绵羊 SNP 芯片上的任何其他单个 SNP。根据估计的育种值，与野生型公羊的女儿相比，AI 公羊纯合 c.1111A 的女儿将至少多产 0.46-0.57 只羔羊。
我们在 GDF9 蛋白的生物活性部分发现了一个错义突变，该突变与 NWS 的产羔数密切相关。根据 NWS 的育种历史和自 1983 年以来 AI 公羊群体中 c.1111A 等位基因频率的显著增加，我们假设 c.1111A 等位基因起源于 1970 年左右引入挪威的芬兰本土品种。由于芬兰本土品种的广泛使用，以及报告称 c.1111A 等位基因纯合的母羊具有繁殖力，我们预计该突变的商业影响将会很大。
