Xiaoqin Huang

Distribution of HLA-A, -B, -Cw, and -DRB1 alleles and haplotypes in an isolated Han population in Southwest China

In this study, polymorphisms of human leukocyte antigen (HLA) class I (A, B, and Cw) and class II (DRB1) loci were analyzed in an isolated Han population living in Fengyandong in the Yunnan province of Southwest China (FYDH) using a high-resolution polymerase chain reaction-Luminex typing method. A total of 13 A, 26 B, 15 Cw, and 23 DRB1 alleles of HLA were found in FYDH. The frequencies of A*1101, A*0207, A*2402, B*4601, B*1502, Cw*0102, Cw*0801, DRB1*0901, and DRB1*1202 were >10%. The following haplotypes were common with frequencies >5%: three A-B, four Cw-B, two B-DRB1, two A-B-DRB1, three A-B-Cw, two B-Cw-DRB1, and two A-B-Cw-DRB1 phylogenetic tree and multidimensional scaling analysis based on HLA-A, -B, and -DRB1 allele frequencies of 18 Han populations suggested that FYDH was an isolated Han population, but the analytic result also provided a suggestion that FYDH was genetically related to Chinese Southern Han. According to the characteristics of the HLA allele and haplotype distributions and significantly reduced allelic and haplotypic diversity in FYDH, we deduced that genetic drift and/or selection and subsequent geographic isolation had influenced the distribution characteristics of the HLA gene in FYDH. In addition, significantly reduced allelic and haplotypic diversity in FYDH makes it an ideal homogenous population and very useful model for future investigations of issues related to immunogenetic diseases in the Han population.

Polymorphisms of human leucocyte antigen genes in Maonan people in China

Abstract We examined human leucocyte antigen (HLA) gene polymorphisms in the Maonan people from southern China. HLA‐A, ‐B and ‐DRB1 alleles were determined in 108 healthy unrelated Maonan individuals by the polymerase chain reaction‐Luminex method, and haplotype frequencies for HLA‐A, ‐B and ‐DRB1 loci were estimated. The most frequent HLA‐A alleles were A*1101 (35.2%), A*0203 (17.6%), A*0207 (13.4%) and A*2402 (13.4%); HLA‐B alleles were B*1301(19.9%), B*1502 (14.8%), B*4601 (13.4%) and B*4001 (13.4%); HLA‐DRB1 alleles were DRB1*1202 (17.1%), DRB1*1602 (13.0%) and DRB1*1401 (10.7%). The most common haplotypes were A*0207‐B*4601 (10.6%), A*1101‐B*1301 (10.0%), A*1101‐B*4001 (8.4%), B*1502‐DRB1*1202 (12.0%), B*4601‐DRB1*1401 (5.8%), A*1101‐B*1502‐DRB1*1202 (7.1%) and A*0207‐B*4601‐DRB1*1401 (5.3%), profiles that are also found in populations from the southern region of East Asia. Phylogenetic and principal component analyses revealed that the Maonan people belong to the southeastern Asian group and are most closely related to the Buyi people.

Differences in mtDNA whole sequence between Tibetan and Han populations suggesting adaptive selection to high altitude.

We performed a mitochondrial whole-genome comparison study in 40 Tibetan and 50 Han Chinese. All subjects could be classified into 13 haplogroups pertained to the Macrohaplogroup M and N that pitched different quadrants by principal component analysis. We observed a difference in the M9 haplogroup and identified 18 significant variants by comparing whole sequences between Tibetan and Han populations. Variants in ND2, COX2, tRNA alanine and 12S rRNA were predicted to confer increased protein stability in Tibetans. We compared the base substitutions of nonsynonymous (NS) versus synonymous (S) of 13 protein-encoding genes and found the NS/S values of the ATP6, ATP8, and Cyt b genes were larger (>1) in Tibetans than that in Han population. Our findings provide clues for the existence of adaptive selection for the ATP6, ATP8, Cyt b, ND2, COX2, tRNA alanine and 12S rRNA genes in Tibetans which likely contributed to adaptation to their specific geographic environment, such as high altitude.

Genetic link among Hani, Bulang and other Southeast Asian populations: evidence from HLA -A, -B, -C, -DRB1 genes and haplotypes distribution.

Human leucocyte antigen (HLA) genetic characteristic of different ethnic minorities would be useful for tracing the origin of modern human HLA matching in transplantation and disease associations. In this study, we reported HLA‐A, ‐B, ‐C and ‐DRB1 alleles and haplotypes in the Bulang and Hani populations of southwestern China using a high‐resolution polymerase chain reaction‐Luminex (PCR‐Luminex) typing method. A total of nine HLA‐A, 22 HLA‐B, 13 HLA‐C and 18 HLA‐DRB1 alleles were identified in the Bulang population, and 11 HLA‐A, 25 HLA‐B, 14 HLA‐C and 19 HLA‐DRB1 alleles were in the Hani population. Compared with other populations, the predominant A*1101‐B*1502‐DRB1*1202 haplotype in the Bulang and Hani populations was also common in Jinuo, Wa, Dai, Maonan and Vietnamese populations. The distribution of HLA genes indicate that Bulang and Hani populations belong to the Southeast Asia group and they have maintained their original genetic characteristics and kept a long genetic distance from other populations owing to founder effects and subsequent geographic isolation. In addition, the close relationship among ethnic groups in Yunnan province and the Thai and Vietnamese populations were confirmed, whereas the Mon‐Kmer‐speaking populations shared other common HLA alleles and haplotypes compared with other linguistic groups.

The association between HLA‐A, ‐B alleles and major histocompatibility complex class I polymorphic Alu insertions in four populations in China

The study of the association between polymorphic Alu insertions [human leukocyte antigen (HLA)-Alu] at five loci and HLA class I alleles at two loci allows for better identification of the origins and evolution of HLA class I region haplotypes in different populations. In the present study, we determined the frequencies of five HLA-Alus and their associations with HLA-A and -B alleles in Han, Wa, Maonan, and Jinuo populations. Our results showed a strong association between AluHG insertion and HLA-A*02 in all populations studied; however, the associations between AluHJ insertion and HLA-A*1101 and HLA-A*2402 and AluHF insertion and HLA-A*2601 were only observed in Han. The AluMICB insertion showed a strong association with HLA-B*5502 in Han, Maonan, and Jinuo. HLA-A*0101, HLA-A*0201, HLA-A*0203, HLA-A*1101, HLA-A*2402, HLA-A*2601, and HLA-A*3101 alleles were associated with one or more of the three different Alu elements within the alpha block as independent haplotypes, and HLA-A*0101, HLA-A*0201, HLA-A*0203, HLA-A*1101, and HLA-A*2402 alleles were associated with at least two different Alu insertions as a haplotype within the alpha block. We conclude that the HLA class I region haplotypes of the four populations were derived from different progenitor haplotypes, and relatively high rates of recombination between individuals with HLA-A alleles and different HLA-Alus occurred in this region.

Distinct HLA allele and haplotype distributions in four ethnic groups of China

Distinct human leukocyte antigen (HLA) allele and haplotype distributions occur in the northern and southern Han populations of China. However, different ethnic groups in China show limited regional distributions for many HLA alleles and haplotypes. Therefore, it is necessary and meaningful to study the differences in HLA allele and haplotype distribution for northern and southern ethnic groups of China. A total of 428 unrelated individuals from the Lisu, Nu, Tu and Yugur ethnic populations were genotyped for HLA-A, -B, -C and -DRB1 alleles using the PCR-Luminex typing method. The frequencies of HLA alleles and statistically inferred haplotypes were calculated. A total of 29 HLA-A, 54 HLA-B, 27 HLA-C and 41 HLA-DRB1 alleles were spread throughout these four populations with distinct allele and deduced haplotype frequencies between populations. Some alleles and deduced haplotypes exhibited significantly different distributions between northern (Tu and Yugur) and southern groups (Lisu and Nu). A phylogenetic tree and principal component analysis were used to compare the HLA polymorphism between our dataset and 19 other eastern and southeastern Asian populations. This analysis showed that Lisu and Nu belong to a cluster of southern ethnic groups, while Tu and Yugur are most closely related to other northern groups. Thus, distinct ethnic population histories were revealed by analyzing HLA allelic polymorphisms with the HLA profiles of the Lisu and Nu southern Chinese ethnic groups clearly different from the Tu and Yugur northern ethnic groups. The results will be useful for future association studies of infectious disease and contribute toward a more efficient search of organ/tissue matches for transplantation.

Autosomal STRs Provide Genetic Evidence for the Hypothesis That Tai People Originate from Southern China

Tai people are widely distributed in Thailand, Laos and southwestern China and are a large population of Southeast Asia. Although most anthropologists and historians agree that modern Tai people are from southwestern China and northern Thailand, the place from which they historically migrated remains controversial. Three popular hypotheses have been proposed: northern origin hypothesis, southern origin hypothesis or an indigenous origin. We compared the genetic relationships between the Tai in China and their “siblings” to test different hypotheses by analyzing 10 autosomal microsatellites. The genetic data of 916 samples from 19 populations were analyzed in this survey. The autosomal STR data from 15 of the 19 populations came from our previous study (Lin et al., 2010). 194 samples from four additional populations were genotyped in this study: Han (Yunnan), Dai (Dehong), Dai (Yuxi) and Mongolian. The results of genetic distance comparisons, genetic structure analyses and admixture analyses all indicate that populations from northern origin hypothesis have large genetic distances and are clearly differentiated from the Tai. The simulation-based ABC analysis also indicates this. The posterior probability of the northern origin hypothesis is just 0.04 [95%CI: (0.01–0.06)]. Conversely, genetic relationships were very close between the Tai and populations from southern origin or an indigenous origin hypothesis. Simulation-based ABC analyses were also used to distinguish the southern origin hypothesis from the indigenous origin hypothesis. The results indicate that the posterior probability of the southern origin hypothesis [0.640, 95%CI: (0.524–0.757)] is greater than that of the indigenous origin hypothesis [0.324, 95%CI: (0.211–0.438)]. Therefore, we propose that the genetic evidence does not support the hypothesis of northern origin. Our genetic data indicate that the southern origin hypothesis has higher probability than the other two hypotheses statistically, suggesting that the Tai people most likely originated from southern China.

Diversity of killer cell immunoglobulin-like receptor genes in four ethnic groups in China

Killer cell immunoglobulin-like receptors (KIRs) show extensive variation in terms of gene content and allelic polymorphisms among different populations. The aim of this study was to analyze the distribution of KIR genes in the Bulang, Nu, Yugu, and Zhuang ethnic groups, which belong to four different language families in China, and thus to provide basic KIR gene and genotype data for these Chinese ethnic groups. Genotyping of 16 KIR genes was performed in 425 unrelated individuals using the polymerase chain reaction–sequence-specific oligonucleotide probe method with the Luminex MultiAnalyte Profiling System. The four framework KIR genes were detected in all four ethnic groups. The activating KIR genes as well as the inhibitory KIR genes showed extreme diversity among these four populations. A total of 35 distinct KIR genotypes were identified, one of which was previously unknown. The four most common genotypes were identified in all four populations and comprised 66.1~91.1% of all the genotypes. The group A haplotype occurred more frequently than the group B haplotype in the Nu, Yugu, and Zhuang populations, as in other East Asian populations. In contrast, the group A and group B haplotypes occurred equally in the Bulang population. The results of the present study suggested that the KIR genes and genotypes are diverse in these four ethnic groups, and each ethnic group has its own characteristic KIR distribution. The findings with respect to KIR gene diversity in these four populations should provide relevant genomic diversity data for the future study of viral infections, autoimmune diseases, and reproductive fitness.

The association and differentiation of MHC class I polymorphic Alu insertions and HLA-B/Cw alleles in seven Chinese populations

We investigated polymorphic Alu insertion (POALIN) frequencies at five loci in the major histocompatibility complex (MHC) class I genomic region to determine their allele and haplotype frequencies and associations with the human leukocyte antigen (HLA)-B and -Cw genes in seven different Chinese ethnic populations, the Han, Bulang, Wa, Dai, Maonan, Hani and Jinuo. The POALINs varied in frequency between 0% and 42.3% with significant differences between populations at all of the loci. Each POALIN was in significant linkage disequilibrium with a variety of HLA-B or -Cw four-digit alleles. The percentage association between Alu insertions and the HLA-B or -Cw alleles was calculated in pairwise analyses of haplotypes to show possible crossing over events between loci. The POALIN insertions also helped to further stratify the HLA-B:-Cw haplotypes into different POALIN:HLA-B:HLA-Cw haplotype frequencies. Of the two-locus, five-locus and seven-locus haplotype analyses, the seven-locus haplotypes showed the largest number of differences between the populations. The most common multilocus haplotype in Han was MICB*1:B*4601:Cw*0102:TF*1:HJ*1:HG*2:HF*1 (15.6%) associated with the AluHG insertion, whereas the second most common multilocus haplotype in Han was MICB*1:B*1502:Cw*0801:TF*1:HJ*2:HG*1:HF*1 (11.8%) associated with the AluHJ insertion. This comparative study of multilocus POALINs in the HLA class I region of seven Chinese ethnic populations shows that POALINs alone or together with the HLA class I alleles are informative genetic markers for the identification of HLA class I allele and haplotype lineages and variations such as crossing over events within the same and/or different populations.

HLA polymorphism of the Zhuang population reflects the common HLA characteristics among Zhuang-Dong language-speaking populations

A study of the human leukocyte antigen (HLA) genetic characteristics in the Zhuang, the largest ethnic population in China, would provide insight into Zhuang history and give a useful tool for disease associations, transplantation, and anthropology. In the present study, we report the comprehensive HLA-A, HLA-B, HLA-C, and HLA-DRB1 alleles and haplotypes in the Zhuang population of southern China for the first time. A total of 13 HLA-A, 24 HLA-B, 22 HLA-C, and 18 HLA-DRB1 were identified in 104 Zhuang individuals. The frequencies of HLA-A*11:01, A*02:07, A*24:02, A*02:03, and A*33:03 on A loci, B*15:02, B*58:01, B*46:01, and B*13:01 on B loci, C*03:04, C*08:01, C*01:02, C*03:02, and C*07:02 on C loci, and DRB1*15:01, DRB1*16:02, DRB1*14:01, DRB1*15:02, and DRB1*03:01 on the DRB1 loci were S>10%. The A*33:03-C*03:02-B*58:01-DRB1*03:01 and A*02:07-C*01:02-B*46:01-DRB1*14:01 haplotypes were predominant in the Zhuang. The phylogenetic tree, as well as the analysis of haplotypes, suggested that the Zhuang are genetically similar to southern Chinese populations, especially the Zhuang-Dong language-speaking populations, such as the Bouyei, Dai, and Maonan. Even though the Zhuang and southern Chinese populations shared common alleles and haplotypes, the Zhuang has maintained its unique genetic characteristics.