Analysis of Y-chromosomal biallelic polymorphisms in Sichuan Han of Chinese population]

OBJECTIVE: To evaluate the forensic utility of Y-single nucleotide polymorphisms (SNPs) markers. METHODS: Allele-specific PCR, restriction enzyme digestion or direct PCR were performed to examine 10 different SNP loci on Y chromosome, namely M9, M15, M45, M89, M95, M122, M134, M145, M173 and P25 in 161 Chinese Han males. RESULTS: A total of 8 of the 10 SNPs are reported to be polymorphic in Chinese. The gene diversity for the loci showing polymorphism ranged from 0.988/0.012-0.752/0.248, with a power of discrimination 0.094-0.373. Loci M122 and M134 were the most polymorphic markers in Chinese Hans. Nine different haplogroups with frequencies from 1.2% to 51.6% were observed and 3 of the haplogroups-K*(x O2a, O3, P), O3*(x O3e) and O3e were found in 75.2% of Chinese Hans. CONCLUSION: A comprehensive gene diversity data of Y chromosome and haplogroups were obtained in Sichuan Han population, which will be served as the base for using these Y-SNP markers in forensic medicine and individual identification in Sichuan Hans.     

Y-chromosome polymorphisms define the origin of the Mang,an isolated population in China

The Mang is an isolated population living at the border of Vietnam and China characterized by small stature and a primordial lifestyle. However, the origin of this population remains unclear. To clarify the origin of the Mang and its genetic relationship with other populations, 20 Y-chromosome markers were analyzed, including 12 biallelic markers and eight short tandem repeats (STR) in this population, and the data compared with published data from other populations in eastern Asia. Only three Y-chromosome haplogroups, O2a*-M95, O3d-M7 and O3e-M134, were identified in Mang. Among them, the southern haplogroups O2a*-M95 were most prevalent, with a frequency of 97%. Principal component analysis (PCA) plots showed that Mang clustered with southern populations but not with northern populations. In conclusion, the present study provided evidence for the first time that the Mang population is of southern origin.     

Y-chromosome polymorphisms define the origin of the Mang, an isolated population in China

The Mang is an isolated population living at the border of Vietnam and China characterized by small stature and a primordial lifestyle. However, the origin of this population remains unclear. To clarify the origin of the Mang and its genetic relationship with other populations, 20 Y-chromosome markers were analyzed, including 12 biallelic markers and eight short tandem repeats (STR) in this population, and the data compared with published data from other populations in eastern Asia. Only three Y-chromosome haplogroups, O2a*-M95, O3d-M7 and O3e-M134, were identified in Mang. Among them, the southern haplogroups O2a*-M95 were most prevalent, with a frequency of 97%. Principal component analysis (PCA) plots showed that Mang clustered with southern populations but not with northern populations. In conclusion, the present study provided evidence for the first time that the Mang population is of southern origin.     

Reduced genetic structure of the Iberian peninsula revealed by Y-chromosome analysis: implications for population demography

Europe has been influenced by both intra- and intercontinental migrations. Since the Iberian peninsula was a refuge during the Last Glacial Maximum, demographic factors associated with contraction, isolation, subsequent expansion and gene flow episodes have contributed complexity to its population history. In this work, we analysed 26 Y-chromosome biallelic markers in 568 chromosomes from 11 different Iberian population groups and compared them to published data on the Basques and Catalans to gain insight into the paternal gene pool of these populations and find out to what extent major demographic processes account for their genetic structure. Our results reveal a reduced, although geographically correlated, Y-chromosomal interpopulation variance (1.2%), which points to a limited heterogeneity in the region. Coincidentally, spatial analysis of genetic distances points to a focal distribution of Y-chromosome haplogroups in this area. These results indicate that neither old or recent Levantine expansions nor North African contacts have influenced the current Iberian Y-chromosome diversity so that geographical patterns can be identified.     

HLA haplotypes and microsatellite polymorphisms in and around the major histocompatibility complex region in a Native American population with a high prevalence of scleroderma (systemic sclerosis)

Choctaw Native Americans in southeastern Oklahoma have the highest prevalence of scleroderma or systemic sclerosis yet found (469/100,000). An Amerindian HLA DR2 haplotype (DRB1*1602) was significantly associated with scleroderma in this population in a previous study. It is not known, however, if other disease genes are linked to this HLA haplotype. The regions flanking the HLA loci were studied with polymorphic microsatellite markers. An extended HLA DR2 (DRB1*1602, DQA1*0501, DQB1*0301, DPB1*1301) haplotype that includes the class I and III regions was identified which was significantly associated with scleroderma in the Oklahoma Choctaw. No other significant associations with microsatellite marker alleles immediately flanking the HLA region were found.     

Y-chromosome genetic variation in Rio de Janeiro population.

The present-day Brazilian gene pool is known to be the outcome of an admixture process of populations from different origins, mainly Amerindians, Europeans, and Africans. It is also known that in Brazil, a wide variation in the admixture process occurred in different regions of the country or even in different subpopulations from the same region. In the present study, we aimed to characterize the male lineages present in the Rio de Janeiro population, the second most populated of the 26 Brazilian states. A random sample of 127 unrelated males from Rio de Janeiro was typed for 28 Y-chromosome-specific biallelic markers. In total, 17 different haplogroups were defined within our sample, most of them of European ancestry (88.1%). Those of sub-Saharan African origin (E3a) amounted to 7.9%, while only 2 males carried Amerindian lineages (characterized by the presence of an M3 mutation: haplogroup Q3). Using both Y-STR haplotype and Y-SNP haplogroup information, genetic distances were calculated between the subgroup of Rio de Janeiro males carrying European haplogroups and the Portuguese population. Low, nonsignificant, values were obtained. Thus, in contrast with what is observed in their female counterparts, the vast majority of the present Rio de Janeiro male gene pool is of European extraction, while the original Amerindian lineages are residual and much less frequent than the sub-Saharan component resulting from the slave trade. These observations can be interpreted as the signature of the strong gender asymmetry of the admixture processes in colonial systems.     

中国四川汉族人群Y染色体单核苷酸多态性分析

目的 评估Y染色体单核苷酸多态性(single nucleotide polymorphisms,SNPs)遗传标记的法医学应用价值.方法 用等位基因特异性PCR,限制性酶切和直接扩增法检测了161名中国四川汉族人Y染色体上10个SNPs位点M9,M15,M45,M89,M95,M122,M134,M145,M173和P25的多态性.结果 有8个位点发现遗传多态性,多态性频率0.988/0.012～0.752/0.248.个人识别能力0.094～0.373,累积个人识别能力为0.8308,M122和M134在中国四川汉族人群中的多态性最高.按照国际Y染色体学会的命名原则,10个位点命名了9种单倍组型,单倍组型频率1.2%～52.2%,其中75.2%的中国四川汉族人主要是K*(XO2a,O3,P),O3*(XO3e)和O3e 3种单倍组型.结论 该研究获得了中国四川汉族人群Y染色体的10个SNPs位点的多态性频率分布及其构建的9种单倍组型,为Y-SNPs做为法医遗传学个人识别和亲子鉴定的遗传标记奠定了基础.     

Patterns of human diversity, within and among continents, inferred from biallelic DNA polymorphisms

Previous studies have reported that about 85% of human diversity at Short Tandem Repeat (STR) and Restriction Fragment Length Polymorphism (RFLP) autosomal loci is due to differences between individuals of the same population, whereas differences among continental groups account for only 10% of the overall genetic variance. These findings conflict with popular notions of distinct and relatively homogeneous human races, and may also call into question the apparent usefulness of ethnic classification in, for example, medical diagnostics. Here, we present new data on 21 Alu insertions in 32 populations. We analyze these data along with three other large, globally dispersed data sets consisting of apparently neutral biallelic nuclear markers, as well as with a beta-globin data set possibly subject to selection. We confirm the previous results for the autosomal data, and find a higher diversity among continents for Y-chromosome loci. We also extend the analyses to address two questions: (1) whether differences between continental groups, although small, are nevertheless large enough to confidently assign individuals to their continent on the basis of their genotypes; (2) whether the observed genotypes naturally cluster into continental or population groups when the sample source location is ignored. Using a range of statistical methods, we show that classification errors are at best around 30% for autosomal biallelic polymorphisms and 27% for the Y chromosome. Two data sets suggest the existence of three and four major groups of genotypes worldwide, respectively, and the two groupings are inconsistent. These results suggest that, at random biallelic loci, there is little evidence, if any, of a clear subdivision of humans into biologically defined groups.     

Native thrombopoietin: structure and function

Thrombopoietin (TPO), the c-Mpl ligand, is produced constitutively in liver and other organs, circulates in the bloodstream, and is delivered to bone marrow, where it stimulates the early development of multiple hematopoietic lineages and megakaryocytopoiesis. The concentration of TPO in blood is regulated by c-Mpl mass on platelets and megakaryocytes. In addition to regulation by the number of TPO molecules, including the possible modulation of TPO mRNA abundance in bone marrow, megakaryocytopoiesis and platelet production may be regulated as a result of modulation of TPO activity by proteolytic processing that generates truncated forms of the molecule. Characterization of TPO partially purified from human plasma, however, revealed that the full-length molecule was the predominant form in the blood of both normal individuals and thrombocytopenic patients, although small amounts of truncated species were detected. Thus, truncation of TPO, at least that in the circulation examined, does not appear to contribute to the direct regulation of platelet production in response to increased demand. Given that native TPO isolated from the plasma of thrombocytopenic animals comprises truncated forms, the truncation of TPO is likely of physiological importance in the life history of this molecule.     

Alu insertion polymorphisms in Native Americans and related Asian populations

BACKGROUND: Alu insertions provide useful markers for the study of inter-population affinities and historical processes, but data on these systems are not numerous in Native Americans and related populations. AIM: The study aimed to answer the following questions: (a) do the population relationships found agree with ethnic, historical and geographical data? and (b) what can heterozygote levels and associated results inform us about the events that led to the colonization of the New World? SUBJECTS AND METHODS: Twelve Alu insertion polymorphisms were studied in 330 individuals belonging to South American Native, Siberian and Mongolian populations. These data were integrated with those from 526 persons, to ascertain the relationships between Asian, Northern Arctic and Amerindian populations. RESULTS: A decreasing trend concerning heterozygosities and amount of gene flow was observed in the three sets, in the order indicated above. Most results indicated the validity of these subdivisions. However, no clear structure could be observed within South American Natives, indicating the importance of dispersive (genetic drift, founder effects) factors in their differentiation. CONCLUSIONS: The answers to the questions are: (a) yes; and (b) an initial moderate bottleneck, intensified by more recent historical events (isolation and inbreeding), can explain the current Amerindian pattern of diversity.     

The phylogenetic and geographic structure of Y-chromosome haplogroup R1a

R1a-M420 is one of the most widely spread Y-chromosome haplogroups; however, its substructure within Europe and Asia has remained poorly characterized. Using a panel of 16 244 male subjects from 126 populations sampled across Eurasia, we identified 2923 R1a-M420 Y-chromosomes and analyzed them to a highly granular phylogeographic resolution. Whole Y-chromosome sequence analysis of eight R1a and five R1b individuals suggests a divergence time of ∼25 000 (95% CI: 21 300–29 000) years ago and a coalescence time within R1a-M417 of ∼5800 (95% CI: 4800–6800) years. The spatial frequency distributions of R1a sub-haplogroups conclusively indicate two major groups, one found primarily in Europe and the other confined to Central and South Asia. Beyond the major European versus Asian dichotomy, we describe several younger sub-haplogroups. Based on spatial distributions and diversity patterns within the R1a-M420 clade, particularly rare basal branches detected primarily within Iran and eastern Turkey, we conclude that the initial episodes of haplogroup R1a diversification likely occurred in the vicinity of present-day Iran.     

Y-chromosome haplogroups and susceptibility to azoospermia factor c microdeletion in an Italian population

Background

A limited number of studies aimed at investigating the possible association of Y‐chromosome haplogroups with microdeletions of the azoospermia factors (AZFs) or with particular infertile phenotypes, but definitive conclusions have not been attained. The main confounding elements in these association studies are the small sample sizes and the lack of homogeneity in the geographical origin of studied populations, affecting, respectively, the statistical power and the haplogroup distribution.

Materials and methods

To assess whether some Y‐chromosome haplogroups are predisposing to, or protecting against, azoospermia factor c (AZFc; b2/b4) deletions, 31 north Italian patients carrying the AZFc b2/b4 microdeletion were characterised for 8 Y‐chromosome haplogroups, and compared with the haplogroup frequency shown by a north Italian population without the microdeletion (n = 93).

Results and discussion

A significant difference was observed between the two populations, patients with microdeletions showing a higher frequency of the E haplogroup (29.3% vs 9.7%, p<0.01). The geographical homogeneity of the microdeleted samples and of the control population, controlled at microgeographical level, allows the possibility that the geographical structure of the Y genetic variability has affected our results to be excluded.

Conclusion

Thus, it is concluded that in the north Italian population Y‐chromosome background affects the occurrence of AZFc b2/b4 deletions.Y‐chromosome long‐arm microdeletions are found in 5–10% of men with severe oligospermia and non‐obstructive azoospermia, and encompass one or more azoospermia factor (AZF) loci. Deletions of the azoospermia factor c (AZFc) region are clearly among the most commonly known molecular causes of spermatogenic failure in men.¹ These deletions are caused by homologous recombination between the 229‐kb‐long b2 and b4 amplicons² and span 3.5 Mb. Eight different gene families are removed by AZFc deletions, including all members of the DAZ gene family, which represents the stronger candidate for the AZFc phenotype.^{1,2,3,4,5,6,7} Although all AZFc deletions are essentially identical in molecular extension, people carrying these microdeletions present variable infertile phenotypes, suggesting the involvement of environmental factors and/or other genetic regions. Furthermore, the function of the AZF genes in human spermatogenesis and the role of the Y‐chromosome background in the predisposition to occurrence of deletions is still largely unknown.At present, around 250 Y single‐nucleotide polymorphisms have been discovered and their phylogenetic relationships are well known.⁸ These polymorphic markers of the male‐specific region of the Y chromosome define monophyletic groups of the Y chromosome, which hereafter we will name as “haplogroups”.A limited number of studies have investigated the possible association of Y‐chromosome haplogroups with microdeletions or with a particular infertile phenotype,⁹ but the contribution of predisposing factors or genetic background to causing deletions is still debated. In particular, only three studies have investigated the possible association between Y‐chromosome haplogroups and AZF deletions,^10,11,12 all of them failing to establish important associations. These works studied such associations in an European population involving 73 microdeleted samples of heterogeneous geographical origin,¹⁰ in a northwestern European population involving 50 patients¹¹ and in a Japanese population, more geographically localised but represented by a very low number of people with microdeletions (six patients).¹² All the previous studies that found some suggestion of an association with Y‐chromosome haplogroups dealt with infertility. They reported a considerable over‐representation of the haplogroup K(xL,N,O1,O3c,P) in Danish men with reduced sperm count, which did not reach significance probably because of a small sample size,¹³ and D2b Y lineage in Japanese men with reduced sperm count,¹⁴ not confirmed by a later study.¹²However, these association studies require particular attention to two principal factors: (1) the geographical structure of the Y‐chromosome variations in the population under investigation, because the Y‐chromosome genetic variability is highly geographically structured and the Y‐haplogroup distribution changes over different geographical areas¹⁵; and (2) the number and selection criteria of the patient and control groups.To assess whether some Y‐chromosome haplogroups predispose to, or protect against, AZFc deletion, we have defined and compared Y‐chromosome haplogroup distribution in a group of unrelated Italian infertile men harbouring the b2/b4 deletion (n = 41, 31 of whom were from north Italy) and in a control group represented by fertile men without microdeletions (fathers of at least one child) from north Italy (n = 93).     

Evolution and migration history of the Chinese population inferred from Chinese Y-chromosome evidence

Y-chromosomes from 76 Chinese men covering 33 ethnical minorities throughout China as well as the Han majority were collected as genetic material for the study of Chinese nonrecombinant Y-chromosome (NRY) phylogeny. Of the accepted worldwide NRY haplogroups, three (haplogroups D, C, O) were significant in this sample, extending previous assessments of Chinese genetic diversity. Based on geographic, linguistic, and ethnohistorical information, the 33 Chinese ethnical minorities in our survey were divided into the following four subgroups: North, Tibet, West, and South. Inferred from the distribution of the newfound immediate ancestor lineage haplogroup O^*, which has M214 but not M175, we argue that the southern origin scenario of this most common Chinese Y haplogroup is not very likely. We tentatively propose a West/North-origin hypothesis, suggesting that haplogroup O originated in West/North China and mainly evolved in China and thence spread further throughout eastern Eurasia. The nested cladistic analysis revealed in detail a multilayered, multidirectional, and continuous history of ethnic admixture that has shaped the contemporary Chinese population. Our results give some new clues to the evolution and migration of the Chinese population and its subsequence moving about in this land, which are in accordance with the historical records.The first two authors contributed equally to this study.     

Y-chromosome specific YCAII, DYS19 and YAP polymorphisms in human populations: a comparative study

Two hypervariable Y-specific markers, the YCAII and DYS19 STRs, and the more stable Y Alu Polymorphism (YAP) have been analysed in about 1400 individuals of 21 different populations, mainly from Europe but also from the Middle East, Africa and Asia. On the basis of the frequency distributions of these three Y-markers we compare, using different statistical analyses, their power in detecting population genetic structure and in distinguishing closely related groups. The pattern of populations' genetic affinities inferred from the three markers considered altogether suggests a strong genetic structure that, with a few exceptions, broadly corresponds to the linguistic relatedness and/or geographic location of the sampled populations.     

温州永嘉汉族人群3个Y-STR基因座的遗传多态性研究

目的研究3个Y染色体STR基因座及其单倍型在温州永嘉人群中的遗传多态性分布,获得相应的群体遗传学数据。方法用复合扩增的方法扩增DYS435、DYS436和DYS4373个基因座,利用聚丙烯酰胺凝胶电泳及银染显带技术进行分型,检测140名无关男性个体单倍型分布。结果3个基因座在该群体中分别检出3、3、4个等位基因,GD值分别是0.5100,0.1490,0.4056,观察到11种单倍型,其单倍型的变异度为0.7042。结论Y-STR基因座复合扩增体系和建立的Y染色体STR数据库,在法医学鉴定中有帮助意义。     

Transient and persistent Helicobacter pylori colonization in Native American children

Helicobacter pylori is chiefly acquired in childhood, but the exact timing of acquisition is not well understood. The main goal of this study was to assess H. pylori acquisition in a pediatric population. We studied two cohorts of Native American children: a birth cohort of 50 children and 58 older children (mean age, 53 months). We measured serum immunoglobulin G (IgG), IgM, and IgA antibodies to H. pylori whole-cell antigen and IgG antibodies to CagA. Among 44 birth cohort children monitored for more than 12 months, 24 (54.5%) had seroconversions, 7 (15.9%) were transient, and 17 (38.6%) were persistent. Among the older children, 49 (84.5%) of the 58 children were monitored for 1 year; 34 (69.4%) had H. pylori antibodies at study entry. During the next year, 7 (20.6%) children seroreverted, and of 15 initially negative children, 5 (33.3%) seroconverted. In both groups, evaluation of CagA antibodies increased the sensitivity of H. pylori detection. Serum pepsinogen I (PGI) levels in H. pylori-negative children rose significantly until age 6 months and remained constant for the next 19 months. At the time of H. pylori seroconversion, PGI peaked to levels significantly higher than in the never-seroconverted (P = 0.02) and the pre-seroconverted (P = 0.03) children, but then declined to levels paralleling those of H. pylori-negative children. Thus, H. pylori acquisition, accompanied by a transient PGI increase, was frequent in this population, especially in the second and third years of life, but often was brief.     

Non-HLA genes modulate the risk of rheumatoid arthritis associated with HLA-DRB1 in a susceptible North American Native population

Most of the genetic risk for rheumatoid arthritis (RA) is conferred by 'shared epitope' (SE), encoding alleles of HLA-DRB1. Specific North American Native (NAN) populations have RA prevalence rates of 2-5%, representing some of the highest rates estimated worldwide. As many NAN populations also demonstrate a high background frequency of SE, we sought to determine whether other genetic factors contribute to disease risk in this predisposed population. RA patients (n=333) and controls (n=490) from the Cree/Ojibway NAN population in Central Canada were HLA-DRB1 typed and tested for 21 single-nucleotide polymorphisms (SNPs) that have previously been associated with RA, including PTPN22, TRAF1-C5, CTLA4, PADI4, STAT4, FCRL3, CCL21, MMEL1-TNFRSF14, CDK6, PRKCQ, KIF5A-PIP4K2C, IL2RB, TNFAIP3, IL10-1082G/A and REL. Our findings indicate that SE is prevalent and represents a major genetic risk factor for RA in this population (82% cases versus 68% controls, odds ratio=2.2, 95% confidence interval 1.6-3.1, P<0.001). We also demonstrate that in the presence of SE, the minor allele of MMEL1-TNFRSF14 significantly reduces RA risk in a dominant manner, whereas TRAF1-C5 increases the risk. These findings point to the importance of non-HLA genes in determining RA risk in a population with a high frequency of disease predisposing HLA-DRB1 alleles.