Analysis Of Several Genes Associated With Human Signs In Jiangsu Han And European Population And The Correlation Between Graves' Disease And CNV

Part ⅠObjective:To explore the difference of several genes associated with human physical features between Jiangsu Han and European populations.Methods:Genotype657,366SNPs were performed by Illumina Human660W-Quad v1.0BeadChip in163Jiangsu Han individuals. Twenty-two SNPs associated with skin pigmentation, hair color, eye color were selected. Analyses were conducted on the differences of allele frequencies between Jiangsu Han and Europeans along with three reference populations (CHB, JPT, YRI). Moreover, the genetic structure was analyzed by multidimensional scaling analysis for the five populations.Results:There are significant allele frequency differences of the19SNPs loci between CHX and CEU, while CHX has significant differences of10and2SNPs with YRI and JPT. Multidimensional scaling analysis showed that the genetic structure of CHX, CHB and JPT were similar, while there was significant genetic structure difference between CHX and CEU, as well as YRI.Conclusion:This study presented the allele frequencies of22SNPs associated with skin pigmentation, hair color, eye color in Han in Jiangsu Province, and revealed the ethnic and geographic differences of these SNPs. Part ⅡObjective:The identification and association study of the copy number variation with pedigree linkage at5q31chromosomal region in Graves’disease (GD).Methods:All samples in this study were recruited from the Chinese Han population through collaboration with multiple hospitals. All cases and controls (1,536GD cases and1,516controls) were recruited from east and north China. All samples were genotyped by Illumina Human660W-Quad BeadChip. After quality controls, B allele frequency and Log R ratio within the5q chromosomal region were extracted from the genotyping results. And these results were calculated as CNVs by using PennCNV and cnvPartition software. Subsequently, association analysis was performed to screen GD associated CNVs by using Plink software. Calculating CNVs through different algorithms has differences, and some CNVs are complementary. We focus on the CNVs of different calculations with overlapping results, the different CNVs in case-control analysis and the CNVs in candidate genes. CNVs associated with Graves’ disease were studied by using bioinformatics analysis and related databases.Results:The association analysis revealed association at loci5q33with the susceptibility of Graves’ disease (P=3.21×10-5). The study of bioinformatics and database shows that the region of chromosome5q31-33is also associated with another kind of autoimmune Crohn’s disease. A large number of research results have been reported that the IRGM upstream fragment missing is the reason for this region association. Although the deletion of this region has been reported in Europe and the United States, it has not been reported among Asians or in the research of Graves’ disease. There are many same susceptibility genes in autoimmune diseases. In this study, we found that CNVs also existed near IRGM gene. Thus, the CNVs of this region are very likely to be GD-related CNVs.Conclusion:The related study of CNV with GD has not been reported at home or abroad. The research in this field is innovative and advanced. In this study, GD-related CNVs were screened by Illumina Human660W-Quad BeadChip. This not only provides new method for future research of GD, but also changes our understanding on the genetic mechanisms of GD.