Data from: Genome-wide association reveals the locus responsible for four-horned ruminant

Phenotypic variability in horn characteristics, such as their size, number and shape, offers the opportunity to elucidate the molecular basis of horn development. The objective of this study was to map the genetic determinant controlling the production of four horns in two breeds, Jacob sheep and Navajo-Churro, and examine whether an eyelid abnormality occurring in the same populations is related. Genome-wide association mapping was performed using 125 animals from the two breeds that contain two- and four-horned individuals. A case–control design analysis of 570 712 SNPs genotyped with the ovine HD SNP Beadchip revealed a strong association signal on sheep chromosome 2. The 10 most strongly associated SNPs were all located in a region spanning Mb positions 131.9–132.6, indicating the genetic architecture underpinning the production of four horns is likely to involve a single gene. The closest genes to the most strongly associated marker (OAR2_132568092) were MTX2 and the HOXD cluster, located approximately 93 Kb and 251 Kb upstream respectively. The occurrence of an eyelid malformation across both breeds was restricted to polled animals and those carrying more than two horns. This suggests the eyelid abnormality may be associated with departures from the normal developmental production of two-horned animals and that the two conditions are developmentally linked. This study demonstrated the presence of separate loci responsible for the polled and four-horned phenotypes in sheep and advanced our understanding of the complexity that underpins horn morphology in ruminants.羊角性状（包括大小、数量与形态）的表型变异，为解析羊角发育的分子机制提供了重要研究契机。本研究旨在定位控制两个绵羊品种——雅各布羊（Jacob sheep）与纳瓦霍丘罗羊（Navajo-Churro）——四角性状形成的遗传决定因子，并探究同一群体中出现的眼睑异常是否与该性状存在关联。本研究选取两个品种中兼具二角与四角个体的125只绵羊开展全基因组关联定位（Genome-wide association mapping）分析，利用绵羊HD SNP基因分型芯片（ovine HD SNP Beadchip）对570712个单核苷酸多态性（Single Nucleotide Polymorphism, SNP）位点进行病例-对照设计分析后，在绵羊2号染色体上检测到显著的关联信号。10个关联度最高的单核苷酸多态性位点均位于131.9~132.6 Mb的基因组区域内，这表明调控四角性状的遗传结构可能仅涉及单个基因。与关联度最高的标记位点（OAR2_132568092）距离最近的基因为MTX2与HOXD基因簇，二者分别位于该位点上游约93 Kb与251 Kb处。在两个绵羊品种中，眼睑畸形仅出现在无角（polled）个体以及角数多于2只的个体中，这表明眼睑异常可能与偏离正常二角个体的发育进程相关，且两种性状在发育层面存在关联。本研究证实了绵羊无角与四角性状分别由不同的基因座调控，并加深了我们对反刍动物羊角形态发育复杂性的理解。