Faculty of Veterinary Science, University of Sydney, Sydney, New South Wales, Australia ; Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
PLoS One. 2013 Sep 30;8(9):e75071. doi: 10.1371/journal.pone.0075071. eCollection 2013.
Coat color and pattern variations in domestic animals are frequently inherited as simple monogenic traits, but a number are known to have a complex genetic basis. While the analysis of complex trait data remains a challenge in all species, we can use the reduced haplotypic diversity in domestic animal populations to gain insight into the genomic interactions underlying complex phenotypes. White face and leg markings are examples of complex traits in horses where little is known of the underlying genetics. In this study, Franches-Montagnes (FM) horses were scored for the occurrence of white facial and leg markings using a standardized scoring system. A genome-wide association study (GWAS) was performed for several white patterning traits in 1,077 FM horses. Seven quantitative trait loci (QTL) affecting the white marking score with p-values p≤10(-4) were identified. Three loci, MC1R and the known white spotting genes, KIT and MITF, were identified as the major loci underlying the extent of white patterning in this breed. Together, the seven loci explain 54% of the genetic variance in total white marking score, while MITF and KIT alone account for 26%. Although MITF and KIT are the major loci controlling white patterning, their influence varies according to the basic coat color of the horse and the specific body location of the white patterning. Fine mapping across the MITF and KIT loci was used to characterize haplotypes present. Phylogenetic relationships among haplotypes were calculated to assess their selective and evolutionary influences on the extent of white patterning. This novel approach shows that KIT and MITF act in an additive manner and that accumulating mutations at these loci progressively increase the extent of white markings.
家畜的毛色和图案变异通常作为简单的单基因特征遗传，但也有一些已知具有复杂的遗传基础。虽然所有物种的复杂性状数据分析仍然是一个挑战，但我们可以利用家畜群体中简化的单倍型多样性来深入了解复杂表型的基因组相互作用。白色面部和腿部标记是马中复杂性状的例子，对其潜在遗传知之甚少。在这项研究中，Franches-Montagnes（FM）马使用标准化评分系统对白色面部和腿部标记的发生情况进行评分。对 1077 匹 FM 马的几种白色图案性状进行了全基因组关联研究（GWAS）。确定了 7 个影响白色标记评分的数量性状位点（QTL），其 p 值 p≤10(-4)。确定了三个位点，MC1R 和已知的白色斑点基因 KIT 和 MITF，是该品种中白色图案范围的主要基因座。这七个位点共同解释了总白色标记评分中 54%的遗传方差，而 MITF 和 KIT 单独解释了 26%。尽管 MITF 和 KIT 是控制白色图案的主要基因座，但它们的影响因马的基本毛色和白色图案的特定身体位置而异。在 MITF 和 KIT 基因座上进行精细作图，以描述存在的单倍型。计算单倍型之间的系统发育关系，以评估它们对白色图案范围的选择和进化影响。这种新方法表明 KIT 和 MITF 以加性方式作用，并且这些基因座上的突变积累逐渐增加白色标记的范围。
