猪先天性外耳发育遗传缺陷致病基因的鉴别

External ear is important part of mammalian audiometric system. External ear malformations have relatively high incidence rates and various types in mammals, often accompanied by hearing disorders. To date few genes related to this malformation have been characterized and the intrinsic pathogenic mechanism of this genetic detect is still elusive.The domestic pig is an ideal biomedical model for human genetic diseases because of the high biological similarity between humans and pigs. We have constructed an Erhualian ×Shaziling F2 inbred population, which showed affected animals with innate auricle malformation. Genetic pedigree analysis revealed that it is autosomal recessive monogenic disease. In this project, we would use this inbred family as experimental animals,and perform genome-wide association study, deep resequencing of target regions, bioinformatic analysis and functional assay, with the aim to identify the pathogenic gene and the causative mutation underlying this genetic disease. The findings will not only provide novel insight into the genetic mechanism of ear malformations in mammals, but also novel diagnostic test for affected animals form Chinese local pig breeds.

耳廓是哺乳动物听力系统的重要组成部分，耳廓畸形发病率较高、类型多样且常伴有听力相关疾病的发生。目前虽已知少部分基因与外耳畸形相关，但其真正的致病机理却鲜有报道。家猪因其生理结构与人高度相似，成为研究人类遗传疾病的理想模式动物。课题组前期获得了一个家猪先天性外耳发育畸形近交家系（二花脸×沙子岭F2家系），通过系谱遗传分析发现此疾病为常染色体单基因隐性遗传性状。本项目拟利用该近交家系为研究材料，采用全基因组关联定位分析和目标区域深度比较重测序，结合生物信息学分析及功能验证，鉴别到导致该疾病的致病基因和因果突变。预期结果不仅将为哺乳动物和人类先天性外耳发育畸形的遗传解析研究提供重要科学借鉴，而且可为中国地方猪种质资源提纯复纯提供新型基因诊断手段。

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