Allele and Haplotype Frequencies of 17 HLA-Related Loci in Shenzhen Chinese Population by Next-Generation Sequencing

Abstract

Although the allele and haplotype frequencies of 11 HLA loci (HLA-A, B, C, DRB1, DRB3/4/5, DQA1, DQB1, DPA1 and DPB1) have been reported in different populations, rare studies have simultaneously assessed the allele distributions of non-classical HLA class I genes (HLA-E/F/G/H) and MICA/MICB together with the 11 classical HLA loci, or further analysed the haplotype frequencies covering the 17 loci. The present study aims to investigate the allele diversity and haplotype frequencies of 17 HLA-related loci including HLA genes and MICA/MICB simultaneously using a hybrid capture (HC)-based NGS method. A total of 358 HLA alleles including 177 class I and 137 class II alleles, as well as 29 MICA and 15 MICB alleles were identified in this project. The most frequent alleles at each locus were A*11:01 (29.10%), B*40:01 (14.46%), C*01:02 (19.90%), DRB1*09:01 (15.61%), DQB1*03:01 (18.48%), DPB1*05:01 (40.13%), DQA1*01:02 (22.58%), DPA1*02:02 (55.27%), DRB3*02:02 (65.95%), DRB4*01:03 (95.20%), DRB5*01:01 (75.97%), E*01:03 (62.63%), F*01:01 (97.07%), G*01:01 (70.74%), H*01:01 (35.87%), MICA*010:01 (19.90%) and MICB*005:02 (57.53%), respectively. The haplotype frequencies for different combinations of HLA loci were estimated and linkage disequilibrium (LD) between alleles for all pairs of neighbouring loci were calculated. The most frequent haplotype covering 17 loci was F*01:01-G*01:01-H*01:01-A*02:07-E*01:03-C*01:02-B*46:01-MICA*010:01-MICB*005:02-DRB4*01:03-DRB1*09:01-DQA1*03:02-DQB1*03:03-DPA1*02:02-DPB1*05:01 with a frequency of 3.18%. This is the first study on allelic polymorphism, haplotype inference and LD covering 17 HLA-related loci simultaneously in the Shenzhen Chinese population. These results will extend our knowledge of the allelic diversity of the HLA complex and provide population genetics data for transplantation and HLA-associated disease studies.