F.-M. Zhu

Analysis for complete genomic sequence of HLA-B and HLA-C alleles in the Chinese Han population

In the present study, we have determined the complete genomic sequence and analysed the intron polymorphism of partial HLA‐B and HLA‐C alleles in the Chinese Han population. Over 3.0 kb DNA fragments of HLA‐B and HLA‐C loci were amplified by polymerase chain reaction from partial 5′ untranslated region to 3′ noncoding region respectively, and then the amplified products were sequenced. Full‐length nucleotide sequences of 14 HLA‐B alleles and 10 HLA‐C alleles were obtained and have been submitted to GenBank and IMGT/HLA database. Two novel alleles of HLA‐B*52:01:01:02 and HLA‐B*59:01:01:02 were identified, and the complete genomic sequence of HLA‐B*52:01:01:01 was firstly reported. Totally 157 and 167 polymorphism positions were found in the full‐length genomic sequence of HLA‐B and HLA‐C loci respectively. Our results suggested that many single nucleotide polymorphisms existed in the exon and intron regions, and the data can provide useful information for understanding the evolution of HLA‐B and HLA‐C alleles.

Analysis of the complete genomic sequence of HLA-A alleles in the Chinese Han population

To analyse the complete genomic sequences and investigate the intron polymorphism of the human leucocyte antigen (HLA)‐A locus, the full‐length nucleotide sequences of each major allelic group of HLA‐A in the Chinese Han population were determined, including HLA‐A*01, A*02, A*03, A*11, A*23, A*24, A*26, A*29, A*30, A*31, A*32, A*33, A*34, A*68, A*69. More than 3.0‐kb DNA fragment of HLA‐A locus was amplified from 5′‐untranslated region to 3′‐noncoding region for sequencing. Full‐length sequences of the HLA‐A alleles were determined using an ABI BigDye® Terminator Cycle Sequencing kit and the HLA‐A phylogenetic tree was analysed by dnaman software. Full‐length nucleotide sequences of 15 HLA‐A alleles (GenBank Accession numbers EU445470–EU445484) were obtained. HLA‐A*110101, A*2301, A*300101, A*310102, A*330301, A*340101, A*680102 and A*6901 alleles were firstly reported for complete genomic sequences. Total 247 polymorphism positions were found in the complete genomic sequences of HLA‐A alleles and a insertion of 17 nucleotides within intron 3 was observed in several allelic groups. According to the phylogenetic tree of the full‐length nucleotide sequences, HLA‐A locus was classified into seven major allelic lineages. In this study, complete genomic sequences of common HLA‐A alleles were obtained and the data will help us understand the evolution of HLA‐A.

Identification of a novel HLA-A*33:03:11 allele by polymerase chain reaction sequence-based typing in a Chinese cord blood donor.

HLA‐B*13:83 differs from HLA‐B*13:01:01 by 2 nucleotide substitutions at positions 103 and 106.

Identification of the novel HLA-B*15:257 allele by polymerase chain reaction sequence-based typing in a Chinese individual.

HLA-B*15:257 has one nucleotide change in exon 2 at position 232C>G from B*15:01:01:01.

MICA, MICB Polymorphisms and Linkage Disequilibrium with HLA-B in a Chinese Mongolian Population

In this study, polymorphisms of major histocompatibility complex class I chain‐related genes A and B (MICA and MICB) and human leucocyte antigen (HLA)‐B gene were investigated for 158 unrelated Chinese Mongolian subjects recruited from central Inner Mongolia Autonomous Region, northern China, by polymerase chain reaction–sequence‐based typing (PCR‐SBT) and cloning. Collectively, 79 alleles, including 20 MICA, 12 MICB and 47 HLA‐B alleles, were identified. MICA*008:01 (21.2%), MICB*005:02 (48.1%) and HLA‐B*51:01 (7.91%) were the most common alleles. Significant global linkage disequilibrium (LD) was detected between HLA‐B and MICA, HLA‐B and MICB, and MICA and MICB loci (all P < 0.000001). The most frequent haplotypes were HLA‐B*51:01‐MICA*009:01 (7.28%), HLA‐B*58:01‐MICB*008 (6.96%), MICA*010‐MICB*005:02 (13.92%) and HLA‐B*58:01‐MICA*002:01‐MICB*008 (6.96%). HLA‐B‐MICA haplotypes such as HLA‐B*50:01‐MICA*009:02 were associated with single MICB allele. Some HLA‐B‐MICA haplotypes were associated with multiple MICB alleles, including HLA‐B*51:01‐MICA*009:01. One novel MICB allele, MICB*031, was identified, which has possibly arisen from MICB*002:01 through single mutation event. We also confirmed the existence of a recently recognized MICA allele, MICA*073, whose ethnic origin has not been previously described. Genotype distributions at MICA, MICB and HLA‐B were consistent with a neutrality model. Our results provide new insight into MIC genetic polymorphisms in Chinese ethnic groups. Findings shown here are important from an anthropologic perspective and will inform future studies of the potential role of MIC genes in allogeneic organ transplantation and HLA‐linked disease association in populations of related ancestry.

Identification of the novelHLA-DRB1*08:69allele by polymerase chain reaction sequence-based typing in a Chinese cord blood donor: NEW ALLELE Alerts

HLA-A*33:03:11 differs from A*33:03:01 by one nucleotide substitution in exon 3 at position 531 G>A.

A novel HLA allele, HLA-B*40:227, was identified by polymerase chain reaction sequence-based typing in a Chinese individual.

HLA-DRB1*11:119 has one nucleotide difference from HLA-DRB1*11:25 at position 286 T>A in exon 2.

HLA-A, -B and -DRB1 allele and haplotype frequencies of 8333 Chinese Han from the Zhejiang province, China

The distribution of human leucocyte antigen (HLA) allele and haplotype is varied among different ethnic populations. In this study, HLA‐A, ‐B and ‐DRB1 allele and haplotype frequencies were determined in 8333 volunteer bone marrow donors of Zhejiang Han population using the polymerase chain reaction sequence‐based typing. A total of 52 HLA‐A, 96 HLA‐B and 61 HLA‐DRB1 alleles were found. Of these, the top three frequent alleles in HLA‐A, HLA‐B and HLA‐DRB1 loci, respectively, were A*11:01 (24.53%), A*24:02 (17.35%), A*02:01 (11.58%); B*40:01 (15.67%), B*46:01 (11.87%), B*58:01 (9.05%); DRB1*09:01 (17.54%),DRB1*12:02 (9.64%) and DRB1*08:03 (8.65%). A total of 171 A‐B‐DRB1 haplotypes with a frequency of >0.1% were presented and the five most common haplotypes were A*33:03‐B*58:01‐ DRB1*03:01, A*02:07‐B*46:01‐DRB1*09:01, A*30:01‐B*13:02‐DRB1*07:01, A*33:03‐B*58:01‐RB1*13:02 and A*11:01‐B*15:02‐DRB1*12:02. The information will be useful for selecting unrelated bone marrow donors and for anthropology studies and pharmacogenomics analysis.

Characterization of a novel allele, HLA‐DQB1*06:47

HLA-DQB1*06:47 has one base substitution at position 618C>A in exon 3 from HLA-DQB1*06:02:01.

A novel HLA allele, HLA-C*01:02:18, was identified by polymerase chain reaction sequence-based typing in a Chinese leukemia patient.

HLA-C*01:02:18 shows one nucleotide difference from that of HLA-C*01:02:01 by a single nucleotide substitution at position 474 C>T in exon 3.