强直性脊柱炎患者16号染色体区域遗传易感位点的大家系全基因组测序验证及筛选  

Region of Chromosome 16 Associated with Genetic Susceptibility of Ankylosing Spondylitis:Exome Sequencing and Validation Study of A Family

作　　者：吕青[1] 李秋霞[1] 郑栩琪 林智明[1] 曹双燕[1] 廖泽涛[1] 魏秋静[1] 祁军[1] 方霖楷[1] 古洁若[1] 

机构地区：[1]中山大学附属第三医院风湿免疫科,广东广州510630

出　　处：《中山大学学报（医学科学版）》2015年第1期33-41,共9页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：中山大学临床医学研究"5010计划"项目(2007023)

摘　　要：【目的】前期家系GWAS非参数分析结果提示在16号染色体chr16:27836693-53825488,LOD=1.656。我们选择一个大的中国汉族强直性脊柱炎家系,采用全基因组外显子测序进一步验证和筛选该区的疾病易感基因位点。【方法】选取一个具有47个成员的5代中国汉族强直性脊柱炎大家系,其中先用家系中3名患者(1名男性,2名女性,分属3代)的基因组DNA进行外显子区高通量测序;对于初筛的外显子组测序后所得到的SNP位点进行全家系成员验证,并进行家系患者和非患者成员间比较,及与健康人群数据进行比较。【结果】通过对数据所进行的分析,发现在16号染色体强直性脊柱炎关联区域三个样本共有SNP 165个。对上述165个SNP进行初步筛选后,对其中的位于15个基因的29个SNP位点,在1个AS患者和1个非AS患者中进行初步验证,进而在上述关联区域内得到5个在家系AS患者和其他非AS患者间差异有显著性的SNP位点rs10163354、rs11863236、rs16945916、rs28654935和rs8043751(P<0.05),位于ABCC11基因。【结论】该家系研究提示在16号染色体区域的ABCC11基因变异可能与AS易感性相关,值得扩大样本进一步研究。【Objective】This research selected a Chinese Han family as subject.The candidate region was chr16 ：27836693-53825488,LOD = 1.656,which was found by GWAS.Three family members was included in the exon sequencing（one male an three female,and belongs to three generation）.SNPs were annotated,and validated by Sanger sequencing to find susceptible gene of AS.【Method】 This research included three family members in the exon sequencing（one male an three female,and belongs to three generation）.Sequence all of candidate SNPs in one patient and one health volunteer of this family.The SNPs which were different in patient and healthy volunteer will be sequenced in all of family members.【Result】 Base on the research of our group,165 SNPs were found in the susceptible region of AS.Filter these SNPs and sequence them in all of family members.Five SNPs,rs10163354,rs11863236,rs16945916,rs28654935,and rs8043751,in ABCC11 gene,was found（P 0.05）.【Conclusion】Base on the research of our group,Five SNPs,rs10163354,rs11863236,rs16945916,rs28654935,and rs8043751,in ABCC11 gene,was found.Provide the necessary clue to the future research.

关 键 词：强直性脊柱炎 外显子测序 易感基因 

分 类 号：R593.23[医药卫生—内科学]