https://scholars.lib.ntu.edu.tw/handle/123456789/569556
Title: | Predicting HLA genotypes using unphased and flanking single-nucleotide polymorphisms in Han Chinese population | Authors: | Hsieh, Ai-Ru Chang, Su-Wei PEI-LUNG CHEN Chu, Chen-Chung Hsiao, Ching-Lin WEI-SHIUNG YANG Chang, Chien-Ching Wu, Jer-Yuarn Chen, Yuan-Tsong TIEN-CHUN CHANG CHIAO-LONG HSIAO |
Issue Date: | 2014 | Journal Volume: | 15 | Journal Issue: | 1 | Source: | BMC Genomics | Abstract: | Background: Genetic variation associated with human leukocyte antigen (HLA) genes has immunological functions and is associated with autoimmune diseases. To date, large-scale studies involving classical HLA genes have been limited by time-consuming and expensive HLA-typing technologies. To reduce these costs, single-nucleotide polymorphisms (SNPs) have been used to predict HLA-allele types. Although HLA allelic distributions differ among populations, most prediction model of HLA genes are based on Caucasian samples, with few reported studies involving non-Caucasians.Results: Our sample consisted of 437 Han Chinese with Affymetrix 5.0 and Illumina 550 K SNPs, of whom 214 also had data on Affymetrix 6.0 SNPs. All individuals had HLA typings at a 4-digit resolution. Using these data, we have built prediction model of HLA genes that are specific for a Han Chinese population. To optimize our prediction model of HLA genes, we analyzed a number of critical parameters, including flanking-region size, genotyping platform, and imputation. Predictive accuracies generally increased both with sample size and SNP density.Conclusions: SNP data from the HapMap Project are about five times more dense than commercially available genotype chip data. Using chips to genotype our samples, however, only reduced the accuracy of our HLA predictions by only ~3%, while saving a great deal of time and expense. We demonstrated that classical HLA alleles can be predicted from SNP genotype data with a high level of accuracy (80.37% (HLA-B) ~95.79% (HLA-DQB1)) in a Han Chinese population. This finding offers new opportunities for researchers in obtaining HLA genotypes via prediction using their already existing chip datasets. Since the genetic variation structure (e.g. SNP, HLA, Linkage disequilibrium) is different between Han Chinese and Caucasians, and has strong impact in building prediction models for HLA genes, our findings emphasize the importance of building ethnic-specific models when analyzing human populations. ? 2014 Hsieh et al.; licensee BioMed Central Ltd. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84893019493&doi=10.1186%2f1471-2164-15-81&partnerID=40&md5=8983e496be23a62e5c90fa7dff11f39c https://scholars.lib.ntu.edu.tw/handle/123456789/569556 |
ISSN: | 1471-2164 | DOI: | 10.1186/1471-2164-15-81 | SDG/Keyword: | 3' Flanking Region; 5' Flanking Region; Alleles; Asian Continental Ancestry Group; China; Gene Frequency; Genotype; HapMap Project; HLA Antigens; HLA-B Antigens; HLA-DQ beta-Chains; Humans; Linkage Disequilibrium; Polymorphism, Single Nucleotide |
Appears in Collections: | 基因體暨蛋白體醫學研究所 |
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