Zhaoqing Yang

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.

Mitochondrial haplogroup M9a1a1c1b is associated with hypoxic adaptation in the Tibetans

While hypoxic environment at high altitude remains a major challenge for travelers from low-altitude areas, Tibetans have adapted to the high-altitude environment. Mitochondria are the energy conversion and supplement centers in eukaryotic cells. In recent years, studies have found that the diversity of the mitochondrial genome may have a role in the adaptation to hypoxia in Tibetans. In this study, mitochondrial haplogroup classification and variant genotyping were performed in Tibetan and Han Chinese populations living at different altitudes. The frequencies of mitochondrial haplogroups B and M7 in the high-altitude population were significantly lower compared with those in the low-altitude population (P=0.003 and 0.029, respectively), whereas the frequencies of haplogroups G and M9a1a1c1b in the high-altitude group were significantly higher compared with those in the low-altitude group (P=0.01 and 0.002, respectively). The frequencies of T3394C and G7697A, which are the definition sites of haplogroup M9a1a1c1b, were significantly higher in the high-altitude group compared with that in the low-altitude group (P=0.012 and 0.02, respectively). Our results suggest that mitochondrial haplogroups B and M7 are associated with inadaptability to hypoxic environments, whereas haplogroups G and M9a1a1c1b may be associated with hypoxic adaptation. In particular, the T3394C and G7697A variants on haplogroup M9a1a1c1b may be the primary cause of adaptation to hypoxia.

Correlation between the linguistic affinity and genetic diversity of Chinese ethnic groups

As the world’s most populous nation, China exhibits a population with 56 nationalities. We already know the associations between genetic relationship of these ethnic groups in China and their geographic distributions are closely. However, the correlations between genetic diversity and linguistic affinities have still not been fully revealed in China. To investigate these correlations, 31 populations and 1527 samples were chosen, and the languages of this population covered all of the languages spoken in mainland China (including 8 main linguistic families and 16 subfamilies). The genetic polymorphisms of the populations were investigated using 10 autosomal microsatellites. Five ethnic groups, which included 234 samples, were genotyped in this survey, and the data collected from the other 26 populations were obtained from our previous study. An analysis of molecular variance, principal coordinate analysis, clustering analysis using the STRUCTURE and the Mantel test were used to investigate the correlations between genetic diversity and linguistic affinity. These analyses indicated that most populations who speak the same language demonstrate a similar genetic composition, although a few populations deviated from this linkage between genetics and language. The demographic histories of these populations who deviated from this linkage were investigated. Obvious reasons for why evolutionary processes of genetics and linguistics separated in these populations included geographic isolation, gene replacement, language replacement and intermarriage. Thus, we proposed that the consistency of genetic and linguistic evolution is still present in most populations in China; however, this consistency can be broken by many factors, such as isolation, language replacement or intermarriage.

Distribution of killer cell immunoglobulin-like receptor genes and combinations with HLA-C ligands in an isolated Han population in southwest China.

Human natural killer cells express killer cell immunoglobulin-like receptors (KIRs), which interact with human leukocyte antigen (HLA) class I molecules. KIR/HLA combinations play an important role in innate and adaptive immunity. In the current study, 16 KIR genes were analyzed in an isolated Han group living in the Fengyandong (FYDH) region in the Yunnan province of southwest China. The framework KIR genes 3DL2, 3DL3, 3DP1, and 2DL4 were found in all individuals. A total of 22 distinct KIR genotypes were observed, four of which were unknown previously. Genotype 1 (N = 52, 55.9%) was the predominant genotype. Analysis of inhibitory and activating KIR and HLA-C ligands showed that all individuals displayed at least one inhibitory or activating KIR/HLA-C pair. One KIR/HLA-C pair was the most frequent (67/93), followed by two pairs (21/93), and three pairs (6/93). The comparison of KIR and HLA frequencies between FYDH and a local Han population showed that the two populations showed similar frequencies for the KIR genes. In contrast, the distribution of HLA alleles and haplotypes showed significant differences between them.

Strong association of SLC1A1 and DPF3 gene variants with idiopathic male infertility in Han Chinese

Male infertility is a multifactorial syndrome encompassing a wide variety of disorders. In recent years, several genome-wide single-nucleotide polymorphism (SNP) association studies (GWAS) have been performed on azoospermia and/or oligozoospermia in different populations including two GWAS on nonobstructive azoospermia in China; however, the association of SNPs with idiopathic male infertility, especially asthenozoospermia and oligozoospermia, and their correlation with semen parameters are still not clear. To investigate genetic variants associated with idiopathic male infertility (asthenozoospermia, oligozoospermia, and oligoasthenozoospermia) in Chinese Han people, 20 candidate SNPs were selected from GWAS results and genotyped using the Sequenom MassARRAY assay. A total of 136 subfertile men and 456 healthy fertile men were recruited. rs6476866 in SLC1A1 (P = 1.919E-4, OR = 0.5905, 95% CI: 0.447-0.78) and rs10129954 in DPF3 (P = 0.0023, OR = 2.199, 95% CI: 1.311-3.689) were strongly associated with idiopathic male infertility. In addition, positive associations were observed between asthenozoospermia and rs215702 in LSM5 (P = 0.0016, OR = 1.479, 95% CI: 1.075-2.033) and between oligoasthenozoospermia and rs2477686 in PEX10 (P = 0.0011, OR = 2.935, 95% CI: 1.492-5.775). In addition, six SNPs (rs215702 in LSM5, rs6476866 in SLC1A1, rs10129954 in DPF3, rs1801133 in MTHFR, rs2477686 in PEX10, and rs10841496 in PED3A) were significantly correlated with semen quality alterations. Our results suggest that idiopathic male infertility in different ethnic groups may share the same mechanism or pathway. Cohort expansion and further mechanistic studies on the role of genetic factors that influence spermatogenesis and sperm progressive motility are suggested.

Gene frequency and haplotype distribution of hemoglobin E among seven minority groups of Yunnan, China

The aim of this study was to determine the distribution and origin of hemoglobin E (HbE) in seven minority groups from various geographical regions of the malaria‐endemic Yunnan province, southwestern China, which have similar ethnic origins and geographic relationships with HbE‐prevalent populations of Southeast Asian countries.

Molecular characterization of two novel echovirus 18 recombinants associated with hand-foot-mouth disease

Human echovirus 18 (E-18) is a member of the enterovirus B species. To date, sixteen full-length genome sequences of E-18 are available in the GenBank database. In this study, we describe the complete genomic characterization of two E-18 strains isolated in Yunnan, China. Pairwise comparisons of the nucleotide sequences and the deduced amino acid sequences revealed that the two Yunnan E-18 strains had 87.5% nucleotide identity and 96.3–96.5% amino acid identity with the Chinese strain. Phylogenetic and bootscanning analyses revealed the two E-18 strains had the highest identity with other several EV-B serotypes than the other E-18 strains in the P3 coding region, especially, 3B region of the Swine Vesicular disease virus (SVDV) strain HK70, indicated that frequent intertypic recombination might have occurred in the two Yunnan strains. This study contributes the complete genome sequences of E-18 to the GenBank database and provides valuable information on the molecular epidemiology of E-18 in China.

Molecular evolution of two asymptomatic echovirus 6 strains that constitute a novel branch of recently epidemic echovirus 6 in China

BackgroundEchovirus 6 (E6) infections are associated with aseptic meningitis and acute flaccid paralysis (AFP). But some infections, sometimes most of them, are asymptomatic. The mechanism of E6 virulence is unknown. Analyses of the molecular evolution of asymptomatic E6 may help understand why the infections show different manifestations.MethodsNinety-six stool samples of healthy children in Yunnan, China were collected and two E6 strains were isolated from them. The whole genomes of these two E6 strains were sequenced, and their molecular evolution was analyzed.ResultsThe results showed that the two E6 strains may be derived from KJ7724XX strains, which were predominant in AFP patients in Shangdong in 2011. The evolution was accelerated when the two E6 strains formed, although no positive selection site was found. The 11 exclusive mutations on which selection force significantly changed were found in the 2C, 3AB and 3C genes.ConclusionThere are some E6 strains which did not cause the disease in the children of Yunnan. These E6 strains maybe come from a recombinant E6 strain which was associated with the outbreak of AFP in Shangdong in 2011. However, some new mutations were found in the 2C, 3AB and 3C genes of these asymptomatic strains, and these mutations may be constraint by the natural selection and could be potentially responsible for clinical presentations.

The Adaptive Change of HLA-DRB1 Allele Frequencies Caused by Natural Selection in a Mongolian Population That Migrated to the South of China

Pathogen-driven balancing selection determines the richness of human leukocyte antigen (HLA) alleles. Changes in the pathogen spectrum may cause corresponding changes in HLA loci. Approximately 700 years ago, a Mongolian population moved from the north of China to the Yunnan region in the south of China. The pathogen spectrum in the south of China differs from that in the north. In this study, changes in the HLA genes in the Yunnan Mongolian population, as well as the underlying mechanism, were investigated. A sequence-based typing method (SBT) was used to genotype HLA-DRB1 in 470 individuals from two Mongolian populations and another five ethnic groups. Meanwhile, 10 autosomal short tandem repeats (STRs) were genotyped to assess the influence of genetic background on HLA-DRB1 frequencies. The frequencies of certain alleles changed significantly in the Mongolian population that migrated to Yunnan. For example, DRB1*12:02:01 increased from 6.1% to 35.4%. STR analysis excluded the possibility of a recent bottleneck and indicated that 50% of the genetic consistency between northern and southern Mongolians; Tajimas D value for HLA-DRB1 exon2 and dN/dS analysis showed that the HLA-DRB1 genes in both Mongolian populations were under balancing selection. However, the sites under natural selection changed. We proposed that the dramatically change of HLA frequencies in southern Mongolian was caused by a combination of inter-population gene flow and natural selection. Certain diseases specific to the south of China, such as malaria, may be the driving force behind the enhanced DRB1*12:02:01 frequency.