Exome Sequencing Screen Susceptibility Gene Or Loci Of Systemic Lupus Erythematosus In Yunnan Han Population

Objectives:In general,it is considered that genetic foctors,epigenetic modifications and environmental factors are associated with Systemic Lupus Erythematosus?SLE?and caused by genetic and environmental interactions.So,we screen and identify the susceptibility genes or loci of SLE in Yunnan han population by exome sequencing.Methods:SLE patients treated in the in-patient facilities of the first affiliated hospital of Kunming medical university?from the October 2015 to June 2016?were recruited in this study.At the same time,the healthy volunteers in Yunnan han population were selected for control group.After collected individual information,we collected their peripheral blood for extracting genomic DNA.Then the whole exom sequencing?WES?was performed according to Illumina High-Throughput Sequencing Platform Operation Guide.In order to screen and identify the susceptibility genes or loci of SLE,fastQC,sequence mapping,filtration,annotation and bioinformatics analysis were further performed.Results:In total,24 SLE and 23 healthy volunteers were analyzed in this study.There were no significant differences in age or sex between these two groups.Mean read depth was 91X and getting high quality sequences.268 missense?according 18 rare variants,2 frameshift deletion and 1 splicing variant?and 16 InDel were called.GO enrichment analysis and kegg pathway analysis revealed that the functions of these loci were associated with lymphocyte regulation and migration,the body of the oxidative stress,tryptophan metabolism,folic acid,estrogen metabolism and salivary secretion?P<0.01?.Finally,7 variants were selected as candidate susceptibility gene of SLE.Conclusion:the conclusion of this study as follows:1)Candidate SNP including rs143467845?SLC4A5,c.a.2306 g,p.Y 769 c?,rs74740082?ERC1,c.G 1004 a,335 q?p.R,rs2228552?COL16A1,Arthur c.185 a,p.T 62 k?,rs1309282?WDR92,c.a.721 g,p.241 v?and InDel mutations are rs138204694?CCDC54,c.647₆51del,p.Q 216 fs?and rs3217319?ZNF480,c.5₆del,p.L 2 fs?.They probably play an important role in SLE and it is worth for us to perform further confirmatory tests.2)Although GWAS studies at present are more popular,but WES also has higher read depth and lower prices as characteristics.So this study is the first high-throughput sequencing based on the SLE in Yunnan Han population and lay the foundation for further researches in parallel.