人群中自发基因变异频率在不同种族间差异巨大，在不同种族中可鉴定出更多新的自发基因变异。青年大学生人群因暴露于吸烟、饮酒等复杂环境因素中的时间较短，且生活环境、饮食及机体代谢较均一，因此，青年人群血脂异常的遗传变异筛查，更能揭示胆固醇代谢异常的原因。本项目首先测定新疆汉族、维吾尔族及哈萨克族青年大学生人群（18-24岁）的血脂水平，根据低密度脂蛋白胆固醇（LDL-C）水平采用极端表型策略分组，结合9个LDL-C异常家系，利用全外显子组测序与生物信息学分析进行胆固醇代谢关键基因单核苷酸变异（SNV）筛选；对筛选获得的SNV，分别在细胞、动物水平进行功能验证和扩大人群样本、寻找家系进行临床验证；对确定影响动物、人群血脂表型的SNV，深入进行分子机制研究。本项目旨在建立基因变异/功能测定、分子机制/血脂异常表型的研究系统，从遗传/环境多层次水平上阐析新疆不同民族青年人群血脂异常发生机制。

Since the frequency of spontaneous genetic variation was vary in different ethnic groups, it's possible to identify more new genetic mutations in different ethnic groups. As the short time of environmental exposure and the homogeneous level of living environment, diet and body metabolism, the genetic screening for dyslipidemia in adolescents was more likely to reveal the cause of abnormal cholesterol metabolism. In this project, plasma lipoprotein and other lipids were measured in adolescents (18-24 years old) of Han nationality, Uygur nationality and Kazak nationality in Xinjiang. According to the level of LDL-C, they were divided into two groups of extremely high and extremely low. Meanwhile, combined with 9 LDL-C abnormal families, whole-exome sequencing and bioinformatics analysis were used to screen the single nucleotide variation (SNV) of key genes in cholesterol metabolism. For SNV obtained by screening, functional determination and verification were conducted in the animal, and the samples were further expanded with the mutation gene as the unit, and the frequency of functional variation was counted, so as to find the pedigree for clinical verification. Investigating the molecular mechanism of SNV in the phenotype of blood lipid of animals and population. The project establishe genetic variation / function test and molecular mechanism /dyslipidemia phenotype system, to explain pathogenesis of dyslipidemia in the multi-layered level of the gene/ protein / environment.