USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030-2600, USA.
Physiol Genomics. 2012 Aug 17;44(16):787-98. doi: 10.1152/physiolgenomics.00159.2011. Epub 2012 Jul 3.
Significant variation exists for maternal nurturing ability in inbred mice. Although classical mapping approaches have identified quantitative trait loci (QTL) that may account for this variation, the underlying genes are unknown. In this study, lactation performance data among the mouse diversity panel were used to map genomic regions associated with this variation. Females from each of 32 inbred strains (n = 8-19 dams/strain) were studied during the first 8 days of lactation by allowing them to raise weight- and size-normalized cross-foster litters (10 pups/litter). Average daily weight gain (ADG) of litters served as the primary indicator of milk production. The number of pups successfully reared to 8 days (PNUM8) also served as a related indicator of maternal performance. Initial haplotype association analysis using a Bonferroni-corrected, genome-wide threshold revealed 10 and 15 associations encompassing 11 and 13 genes for ADG and PNUM8, respectively. The most significant of these associated haplotype blocks were found on MMU 8, 11, and 19 and contained the genes Nr3c2, Egfr, Sec61g, and Gnaq. Lastly, two haplotype blocks on MMU9 were detected in association with PNUM8. These overlapped with the previously described maternal performance QTL, Neogq1. These results suggest that the application of in silico QTL mapping is a useful tool in discovering the presence of novel candidate genes involved in determining lactation capacity in mice.
近交系小鼠的母性养育能力存在显著差异。尽管经典的图谱绘制方法已经确定了可能导致这种差异的数量性状基因座(QTL),但这些基因仍不清楚。在这项研究中,利用小鼠多样性面板中的泌乳表现数据来绘制与这种差异相关的基因组区域。在泌乳的前 8 天,对 32 个近交系的雌性(n=8-19 只/系)进行研究,让它们喂养体重和大小正常化的交叉寄养窝仔(10 只/窝)。窝仔的平均日增重(ADG)作为产奶量的主要指标。成功饲养到 8 天的窝仔数量(PNUM8)也作为母性表现的相关指标。使用经 Bonferroni 校正的全基因组阈值进行初始单倍型关联分析,发现 ADG 和 PNUM8 分别有 10 个和 15 个包含 11 个和 13 个基因的关联单倍型,其中最显著的关联单倍型块位于 MMU8、11 和 19 上,包含 Nr3c2、Egfr、Sec61g 和 Gnaq 基因。最后,在 MMU9 上检测到与 PNUM8 相关的两个单倍型块。这些与先前描述的母性表现 QTL Neogq1 重叠。这些结果表明,应用计算机 QTL 图谱绘制是发现参与决定小鼠泌乳能力的新候选基因的有用工具。