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三个新的与慢性乙型病毒性肝炎易感性相关的HLA中单核苷酸变异

发表时间:2016-12-15  浏览量:1468  下载量:455
全部作者: 蒋丹华,廖启军,赵强,王一鸣
作者单位: 中山大学中山医学院医学遗传学教研室;中山大学中山医学院疾病基因组研究所;深圳华大基因研究院;中山大学附属第一医院生殖医学中心;中山大学新华学院
摘 要: 目的:从前期已进行全外显子组测序的极端性状个体的数据中挖掘并鉴定人类白细胞抗原(human leucocyte antigen,HLA)基因区域内与慢性乙型病毒性肝炎(乙肝,chronic hepatitis B,CHB)易感性相关的单核苷酸变异(single nucleotide variations,SNV)。方法:选择极端性状的个体,即理论上对乙肝易感的个体99例及对乙肝抵抗的个体90例,对它们进行全外显子组测序,从全外显子组测序数据中筛选出HLA基因区域内所有导致编码蛋白改变的SNV及小的插入缺失(insertion and deletion,INDEL),对其频率的差异进行统计学分析,并对阳性者进行生物信息学研究。结果:本研究在HLA基因区域内发现3个具有统计学意义的SNV,即rs10093、rs12722039、rs12722042(rs10093:P=0.004 2,OR=2.164 6;rs12722039:P=0.001 6,OR=2.512 2;rs12722042:P=0.001 6,OR=2.512 2),它们皆位于单倍体HLA-DQA1*0104内。生物信息学分析显示这3个突变均导致编码蛋白的改变。结论:本研究在HLA区域内发现了3个与乙肝易感性相关的改变基因编码蛋白的SNV,即rs10093、rs12722039、rs12722042. 为进一步研究HLA在CHB中的功能提供了新的基础。
关 键 词: 医学遗传学;慢性乙型病毒性肝炎;全外显子组测序;人类白细胞抗原;单核苷酸变异
Title: Three novel single nucleotide variations in HLA associated with susceptibility to chronic hepatitis B
Author: JIANG Danhua, LIAO Qijun, ZHAO Qiang, WANG Yiming
Organization: Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University; Center for Genome Research, Zhongshan School of Medcine, Sun Yat-sen University; Beijing Genomics Institute (BGI)-Shenzhen; Reproductive Medicine Center, The First Affiliated Hospital, Sun Yat-sen University; Xinhua College, Sun Yat-sen University
Abstract: Objective: Mining from our previous exome sequencing data of extreme phenotypic individuals, to unravel and identify single nucleotide variations (SNV) associated with susceptibility to chronic hepatitis B (CHB) in region of human leucocyte antigen (HLA) genes. Methods: We selected 99 CHB “susceptible” individuals and 90 CHB “resistance” individuals and performed exome sequencing on these individuals. We selected all coding region variations, SNV and small insertion and deletion (INDEL) in the HLA region from the exome sequencing data. We performed statistical analysis to select variations significantly different between the two groups. We further performed haplotype constructionand bioinformatics studies on the significant variations. Results: Three previously unreported novel variations, rs10093, rs12722039 and rs12722042 (rs10093: P=0.004 2, OR=2.164 6; rs12722039: P=0.001 6, OR=2.512 2; rs12722042: P=0.001 6, OR=2.512 2) in the HLA regions were associated with CHB. Our haplotype analysis showed that the three variations were located in the HLA-DQA1*0104. Bioinformatics analysis showed that the three variations damaged the functions of the wild-type alleles. Conclusion: We have discovered three new genetic variations, rs10093, rs12722039 and rs12722042, associated with susceptibility to CHB. This adds novel information on our understandings of HLA in the pathogenesis of CHB.
Key words: medical genetics; chronic hepatitis B; exome sequencing; human leucocyte antigen; single nucleotide variations
发表期数: 2016年12月第23期
引用格式: 蒋丹华,廖启军,赵强,等. 三个新的与慢性乙型病毒性肝炎易感性相关的HLA中单核苷酸变异[J]. 中国科技论文在线精品论文,2016,9(23):2440-2444.
 
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