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中国循证儿科杂志

中国循证儿科杂志 ›› 2016, Vol. 11 ›› Issue (3): 204-209.

• 论著 • 上一篇    下一篇

基于单中心儿童样本库人群全外显子组数据的致病突变携带者分析

林伊凤1，王慧君2，吴冰冰2，杨琳2，董辰2，卢宇蓝2，周文浩3   

  1. 复旦大学附属儿科医院 1 儿科研究所，2 分子诊断中心，3 新生儿科 上海，201102
  • 收稿日期:2016-06-25 修回日期:2016-06-25 出版日期:2016-06-25 发布日期:2016-06-25
  • 通讯作者: 卢宇蓝

Carrier analysis of known disease-causing genes based on WES data from single Shanghai pediatric center

LIN Yi-feng1, WANG Hui-jun2, WU Bing-bing2, YANG Lin2, DONG Chen2, LU Yu-lan2, ZHOU Wen-hao3   

  1. 1 Institute of Pediatrics, 2 Molecular Diagnostic Center, 3 Department of Neonatology, Children′s Hospital of Fudan University, Shanghai 201102, China
  • Received:2016-06-25 Revised:2016-06-25 Online:2016-06-25 Published:2016-06-25
  • Contact: LU Yu-lan

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摘要：

目的 通过对比公共数据库和复旦大学附属儿科医院分子诊断中心（复旦儿科）样本库全外显子组测序（WES）数据中已知儿童致病突变频率差异，推测中国人群隐性遗传致病基因携带者频率分布。方法 整理公共数据库（OMIM、ClinVar、HGMD）中常染色体隐性遗传病的致病基因和突变位点，计算复旦儿科样本库中的WES数据，基于公共数据库的致病基因的携带者频率。结果 从公共数据库分析中共得到1 368个常染色体隐性致病基因上的60 209个位点。在复旦儿科1 147例临床WES样本中，共筛出408个基因上的1 016个突变位点。比较复旦儿科、人类外显子组整合数据库（ExAC）东亚（4 312例）和欧洲人群（33 301例）突变位点的出现频率，3个人群中均发现了人群特有的突变位点，相比ExAC欧洲人群，复旦儿科人群中的突变位点出现频率与ExAC东亚人群更为相近。在携带者频率>1%的基因中，复旦儿科和ExAC东亚人群相同的基因分别为70/81个（86.4%）和70/102个（68.6%）；复旦儿科和ExAC欧洲人群相同的基因分别为37/81个（45.7%）和37/136个（27.2%）。结论 通过与ExAC东亚和欧洲人群数据进行对比，中国人群中隐性致病基因及致病突变位点的携带者频率与ExAC东亚人群较为相似，与欧洲人群差异较大，建立针对中国人群特异性的常见遗传携带者突变位点筛查项目十分必要。

Abstract:

Objective By comparing genotype frequencies among public population databases and single pediatric center, the carrier frequency of autosomal recessive disease-causing genes was acquired in Translational Medicine Center of Children′s Hospital of Fudan University (TMCCHFU). These carrier frequencies could be used as a reference to estimate the Chinese population carrier frequency, and would provide essential information for the design of Chinese-specific disease-causing gene carrier screen panel.Methods The disease-causing autosomal recessive genes from OMIM, and known pathogenic disease-causing mutations from ClinVar and HGMD were summarized. The carrier frequency of disease-causing genes was calculated using local population data and public population databases seperately, and then compared with each other in further studies.Results The public database were filtered and 60 209 pathogenic mutations on 1 368 autosomal recessive disease-causing genes were found, and 1 016 of mutations on 408 genes were identified in 1 147 WES datasets from TMCCHFU. Compared with ExAC East Asian population (4 312 samples) and ExAC European population (33 301 samples), population-specific mutations were identified in each of the populations. Carrier frequencies in TMCCHFU showed more similarity with ExAC East Asian population than European population. Among genes with carrier frequency higher than 1%, 70 out of 81 genes (86.4%) from TMCCHFU overlapped with 70 out of 102 genes (68.6%) from ExAC East Asian population, while 37 out of 81 genes (45.7%) overlapped with 37 out of 136 genes (27.2%) from ExAC European population.Conclusion Through comparison with ExAC East Asian and European population, carrier frequency of disease-causing genes identified in TMCCHFU is much more similar with East Asian population than European population. The difference of carrier frequency among populations should not be ignored and makes it necessary to establish a Chinese-specific panel for genetic disease screen.