Abstract
BackgroundDespite the importance of the human leukocyte antigen (HLA) gene locus in research and clinical practice, direct HLA typing is laborious and expensive. Furthermore, the analysis requires specialized software and expertise which are unavailable in most developing country settings. Recently, in silico methods have been developed for predicting HLA alleles using single nucleotide polymorphisms (SNPs). However, the utility of these methods in African populations has not been systematically evaluated.Methodology/Principal FindingsIn the present study, we investigate prediction of HLA class II (HLA-DRB1 and HLA-DQB1) alleles using SNPs in the Wolaita population, southern Ethiopia. The subjects comprised 297 Ethiopians with genome-wide SNP data, of whom 188 had also been HLA typed and were used for training and testing the model. The 109 subjects with SNP data alone were used for empirical prediction using the multi-allelic gene prediction method. We evaluated accuracy of the prediction, agreement between predicted and HLA typed alleles, and discriminative ability of the prediction probability supplied by the model. We found that the model predicted intermediate (two-digit) resolution for HLA-DRB1 and HLA-DQB1 alleles at accuracy levels of 96% and 87%, respectively. All measures of performance showed high accuracy and reliability for prediction. The distribution of the majority of HLA alleles in the study was similar to that previously reported for the Oromo and Amhara ethnic groups from Ethiopia.Conclusions/SignificanceWe demonstrate that HLA class II alleles can be predicted from SNP genotype data with a high level of accuracy at intermediate (two-digit) resolution in an African population. This finding offers new opportunities for HLA studies of disease epidemiology and population genetics in developing countries.
Highlights
The human leukocyte antigen (HLA) locus, located on chromosome 6p21.3, is the most polymorphic and gene-dense region of the human genome [1]
This study demonstrated high accuracy of two-digit HLA prediction using a small set of single nucleotide polymorphisms (SNPs) in an Ethiopian population
This suggests that HLA prediction may provide a simpler and less expensive alternative to direct typing of HLA genes in an African population
Summary
The human leukocyte antigen (HLA) locus, located on chromosome 6p21.3, is the most polymorphic and gene-dense region of the human genome [1]. The use and acceptance of single nucleotide polymorphism (SNP) genotype data in the HLA region to predict HLA alleles is increasing, especially in non-African populations. This approach is less expensive than classical HLA typing, and in some instances the required SNP data may already have been generated through high-throughput genotyping done for large-scale genomic studies. The high polymorphism of HLA genes, genetic diversity among African populations and resource limitations in these settings present important challenges to direct HLA typing and/or the use of the same set of tag SNPs across different African populations. We describe distributions of HLADRB1 and HLA-DQB1 alleles in our sample using predicted and directly typed HLA data, and compare the allele distributions with available published data from two other Ethiopian ethnic groups, the Amhara and the Oromo
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