强直性脊柱炎一家系全外显子组测序分析

目的： 对一强直性脊柱炎（ankylosing spondylitis，AS）家系进行全外显子测序，筛选该家系的易感基因，为其发病机制提供理论依据。方法： 收集1组AS家系成员的临床资料，其中男性患者2例，年龄分别为48岁和18岁，病程分别为23年和4年。提取相关家系成员外周血DNA进行全外显子测序，测序结果与人类数据库比对，过滤掉同义突变及高频突变，整合家系成员单核苷酸非同义突变，寻找致病基因。结果： 家系成员共得原始数据80 G，数据具有较高质量值，通过对家系患者与正常人测序结果比对分析，同时经过多个生物数据库数据过滤，发现JAK2基因12号外显子上存在的杂合突变c.1709A>G（p.Tyr570Cys）为该家系的可能致病基因突变。另外，该家系MUC3A基因c.1151T>C突变可能是该家系患病成员肠道症状的原因之一。结论： 运用全基因组外显子测序寻找AS易感基因是可行的，JAK2基因c.1709A>G突变可能是导致该家系AS的致病突变及位点。

Whole-exome sequencing in a pedigree with ankylosing spondylitis

Objective: To choose the disease-causing gene in a Chinese pedigree with ankylosing spondylitis (AS) by whole-exome sequencing(WES),and provide theory basis for mechanism of disease.Methods: Clinical data of AS pedigree were collected,including 2 males,the age were 48 and 18 years old,the course of disease were 23 and 4 years. Whole blood genomic DNA of AS was extracted to perform whole-exome sequencing,the results were compared with human databases,common variations which had been reported were wiped out,then non-synonymous single nucleotide variants(SNVs) from the family members were combined,and candidate genes was selected initially.Results: Totally 80 G data was obtained from AS family with high quality. By comparing results between patient and normal subject,and filtering with number of biological database,the result showed heterozygous mutation of JAK2 gene 12 exon c.1709 A>G (p.Tyr570Cys) may be the potential disease-causing gene. The variant c.1151T>C of MUC3A gene may be one of the causes of intestinal symptoms in the family members.Conclusion: It is feasible to find t candidate gene mutations of AS by Exon sequencing. The mutation c.1709 A>G in gene JAK2 identified by whole-exome sequencing might be the pathogenic mutation in this AS pedigree.