Substantial native American female contribution to the population of Tacuarembó, Uruguay,reveals past episodes of sex‐biased gene flow

For many years it has been assumed that the population of Uruguay is almost exclusively European‐derived and that the biological contribution of the native population as well as of individuals of African descent is negligible. Several recent studies based on a variety of genetic markers, mostly morphological and serological markers, have produced quite a different picture of the constitution of the Uruguayan population. The Native American contribution varies from 1–20%, while the African contribution ranges from 7–15%, in different regions of the country. In the present study we examine the way the admixture process took place in Uruguay by analyzing the ancestry of maternal lineages in a sample from the northern city of Tacuarembó. To accomplish this goal we typed mitochondrial DNA (mtDNA) markers of Native American, African, and European origin and estimated the proportions of each parental group in the admixed population. We found that 62% of all mtDNA haplogroups were of Native American descent, a surprising figure considering the “European roots” of the country. Consequently, this result assimilates Uruguay to the rest of Latin American populations where sex‐biased gene flow between European men and Native American women has been the rule. We further analyzed the distribution of the four major founding mitochondrial lineages in Tacuarembó and compared it to other South American populations. We discuss our findings in the light of historical records and assess the need for additional genetic studies. Am. J. Hum. Biol. 16:289–297, 2004. © 2004 Wiley‐Liss, Inc.     

Admixture in the Hispanics of the San Luis Valley, Colorado, and its implications for complex trait gene mapping

Hispanic populations are a valuable resource that can and should facilitate the identification of complex trait genes by means of admixture mapping (AM). In this paper we focus on a particular Hispanic population living in the San Luis Valley (SLV) in Southern Colorado.We used a set of 22 Ancestry Informative Markers (AIMs) to describe the admixture process and dynamics in this population. AIMs are defined as genetic markers that exhibit allele frequency differences between parental populations ≥30%, and are more informative for studying admixed populations than random markers. The ancestral proportions of the SLV Hispanic population are estimated as 62.7 ± 2.1% European, 34.1 ± 1.9% Native American and 3.2 ± 1.5% West African. We also estimated the ancestral proportions of individuals using these AIMs. Population structure was demonstrated by the excess association of unlinked markers, the correlation between estimates of admixture based on unlinked marker sets, and by a highly significant correlation between individual Native American ancestry and skin pigmentation (R²= 0.082, p < 0.001). We discuss the implications of these findings in disease gene mapping efforts.     

HLA disease association and protection in HIV infection among African Americans and Caucasians

In a previous investigation, we demonstrated an increased progression of overt AIDS in the African American population compared to the Caucasian population as reflected by the significantly lower absolute number of CD4+ lymphocytes detected in the African American population in an earlier study. The present study elucidates some of the possible genetic factors which may contribute to disease association or protection against HIV infection. The HLA phenotypes expressed as A, B, C, DR and DQw antigens were revealed by the Amos-modified typing procedure. NIH scoring was utilized to designate positive cells taking up trypan blue. A test of proportion equivalent to the chi 2 approximation was used to compare the disease population (n = 62; 38 African Americans, 24 Caucasians) to race-matched normal heterosexual local controls (323 African Americans, 412 Caucasians). Significant p values were corrected for the number of HLA antigens tested. HLA markers associated with possible protection from infection for African Americans were Cw4 and DRw6, whereas Caucasians expressed none. Disease association markers present in the African American population were A31, B35, Cw6, Cw7, DR5, DR6, DRw11, DRw12, DQw6 and DQw7, whereas in the Caucasian population A28, Aw66, Aw48, Bw65, Bw70, Cw7, DRw10, DRw12, DQw6 and DQw7 were demonstrated. The highest phenotypic frequency for a disease association marker in the study was for HLA-DR5 (62.9%) in the HIV-infected African American population without Kaposi's sarcoma compared to a frequency of 28.9% for the regional control group (p = 0.0012). We conclude that genetic factors do have a role in HIV infection since only 50-60% of those exposed to the AIDS virus will become infected.     

Estimates of interethnic admixture in the Brazilian population using a panel of 24 X‐linked insertion/deletion markers

Objectives. In this study, we aimed to identify ancestry informative haplotypes and make interethnic admixture estimates using X‐chromosome markers. Methods. A significant sample (461 individuals) of European, African, and Native American populations was analyzed, and four linkage groups were identified. The data obtained were used to describe the ancestral contribution of populations from four different geographical regions of Brazil (745 individuals). Results. The global interethnic admixture estimates of the four mixed populations under investigation were calculated applying all the 24 insertion/deletion (INDEL) markers. In the North region, a larger Native Americans ancestry was observed (42%). The Northeast and Southeast regions had smaller Native American contribution (27% in both of them). In the South region, there was a large European contribution (46%). Conclusions. The estimates obtained are compatible with expectations for a colonization model with biased admixture between European men (one X chromosome) and Native American and African women (two X chromosomes), so the 24 X‐INDEL panel described here can be a useful to make admixture interethnic estimates in Brazilian populations. Am. J. Hum. Biol., 2010. © 2010 Wiley‐Liss, Inc.     

Directional mating and a rapid male population expansion in a hybrid Uruguayan population.

The Uruguayan population has been considered as mainly European descent, with a negligible Native American or African contributions. Based on serological and molecular markers, recent studies demonstrate that these two populations had an important influence in the conformation of the present one. To the Northeastern region of Uruguay, a 20% Native American contribution was estimated using autosomal markers and a 62% Native American female origin based on mitochondrial markers. In this paper, we analyze four Y chromosome markers, two biallelic loci (M3 and YAP) and two microsatellites (DYS389I and DYS391), to characterize the male genetic contribution of a sample from the Northeastern city of Tacuarembó. We take different approaches to estimate the origin of male contributions to the population of Tacuarembó; Native American contribution ranges between 1.60% and 8.31%, confirming strong directional mating, which was also detected before with mitochondrial markers. Furthermore, the male population of Tacuarembó presents the characteristic of a population that suffered a bottleneck and a posterior expansion, confirmed using two microsatellite-based statistics to analyze the past population growth; patrilocality and migration could be responsible of those characteristics.     

Different contributions of ancient mitochondrial and Y-chromosomal lineages in 'Karretjie people' of the Great Karoo in South Africa

The Karretjie people of the South African Great Karoo are itinerants who subsist by sheep shearing. Although officially classified 'Coloured', they are aware of their Khoe and San roots. To investigate the maternal and paternal ancestries of the Karretjie people we analyzed their mitochondrial and Y-chromosome DNA variation. Their genetic ancestry was compared with a neighboring group of 'Coloured' individuals. We found that the mitochondrial DNA (mtDNA) haplogroup L0d was present in all the Karretjie people examined, suggesting a maternal contribution, exclusively from the Khoe and San, whereas the paternal ancestry in males was more heterogeneous. The Coloured sample, on the other hand, were found to have a lower frequency of L0d (64.5%), but did harbor other African (27.6%) and non-African (7.9%) mtDNA haplogroups. Similar to the Karretjie people, the Y-chromosome lineages identified in the Coloured group had heterogeneous origins. This study also enabled an assessment of mtDNA variation within L0d sub-haplogroups. All seven of the L0d sub-clades were identified in the combined sample and were used to construct an L0d network.     

Gender bias in the multiethnic genetic composition of central Argentina

A sample of central Argentina (Córdoba) was genotyped for the first hypervariable region (HVS-I) plus a set of coding region mitochondrial DNA (mtDNA) single nucleotide polymorphisms (SNPs) (N = 102) and compared with a data set of Y-chromosome short tandem repeats (Y-STRs; N = 100) previously genotyped in the same individuals. We additionally compiled a database containing more than 4,000, 6,800, and 12,000 HVS-I sequences of Native American, sub-Saharan African, and European origin, respectively. The Y-Chromosome Haplotype Reference Database (YHRD) was used as a reference for the Y-STR profiles from Córdoba. The Native American component is highly prevalent on the maternal side (approximately 41%) in contrast to the Y-chromosome paternal contribution (approximately 2%), indicating a strong gender bias in the colonization and admixture processes that occurred in the recent history of Argentina, in agreement with historical records. The demographic input of African slaves in Córdoba was very high in the eighteenth century (approximately 40% of the total population) but decreased dramatically after a few decades; therefore, the minor traces of sub-Saharan Y-chromosome and mtDNA lineages observed in our sample fit well with these historical records. The European Y-chromosome component of Córdoba (approximately 97%; in contrast to the 57% observed in the mtDNA side) also mirrors the substantial immigration experienced by Argentina during the beginning of the last century, predominantly from Italy and Spain.     

Heterogeneity of the genome ancestry of individuals classified as White in the state of Rio Grande do Sul, Brazil.

One hundred nineteen individuals classified as White, living in different localities of the Brazilian state of Rio Grande do Sul, were studied in relation to the HVS-I region of the mitochondrial DNA (mtDNA). The male fraction of the sample (N = 74) was also tested for seven Y-chromosome polymorphisms. In a specific population (Veranópolis), a city characterized by a large influence of the Italian immigration of the 19th century, the results from the maternal and paternal sides indicated almost complete European ancestry. However, another sample identified as White, from different localities of Rio Grande do Sul, presented significant fractions of Native American (36%) and African (16%) mtDNA haplogroups. These results indicate that Brazilian populations are remarkably heterogeneous; while some present an overwhelming majority of transplanted European genomes, with a complete correspondence between physical appearance and ancestry, others reflect a history of extensive admixture with dissociation between physical appearance and ancestry.     

HLA class II polymorphism in the Ticuna of Brazil: Evolutionary implications of the DRB1*0807 allele

Abstract: The alleles at the HLA class II loci HLA-DRB1, DQA1, DQB1 and DPB1 were determined for 49 individuals of the Ticuna, a Native South American population living in Brazil, using PCR/SSO probe hybridization and DNA sequencing. A newly described DRB1*08 variant, DRBl*0807, which has previously been reported only in native Colombians and contemporary Brazilians of African and Caucasian descent, was identified in the Ticuna at a high frequency (f=0.225). Because *0807 has been observed only in South American populations, we propose that it was generated from a parental *0802 allele recently, after the isolation of various Native South American populations, and infer that the DRB1*0807 allele was generated by a C to T change at codon 57 (Asp→Val, GAT→GTT) from the ancestral *0802. This inference is supported by the sequence of a complex VNTR in the second intron of the DRB1 gene. The DPB1 alleles *0401, *0402 and *1401 constituted 76% of the observed Ticuna DPB1 alleles (f=0.166, 0.427 and 0.166 respectively). In addition, the DPB1 allele *3501, which has been observed in a few other Native South American groups, was observed at a frequency of 0.053 and may have been generated from the putative ancestral allele *1401 allele in South America. The DRB1 and DPB1 allele frequencies for the Ticuna deviate from expected Hardy-Weinberg equilibrium proportions, while DQA1 and DQB1 allele frequencies do not. When this deviation, which involves an observed excess of DRB1*0807 heterozygotes, is considered with the high frequency of the DRB1*0807 and DPB1*1401 alleles, we infer that native South American populations may have been under selection pressure for increased allele diversity.     

四川汉族人群Y染色体单倍组及其特点的研究

目的建立四川汉族人群Y染色体单倍组的分布资料。方法应用PCR-限制性片段长度多态性、变性高效液相色谱技术、DNA测序方法对341份四川汉族男性标本Y染色体18个二态位点进行基因分型。结果共观察到14个Y染色体单倍组,其中H2、H4单倍组在四川汉族中被首次证实,N＊、H14单倍组为中国人群首次报道。四川汉族人群Y染色体单倍组分布频率与已报道的中国南方汉族人群相比差异具有统计学意义。结论该研究获得了更为准确的四川汉族人群的Y染色体单倍组分布频率,为生精障碍、前列腺癌和睾丸癌等男性特异性疾病的Y连锁遗传因素研究奠定了基础。     

Y-chromosome R-M343 African lineages and sickle cell disease reveal structured assimilation in Lebanon

We have sought to identify signals of assimilation of African male lines in Lebanon by exploring the association of sickle cell disease (SCD) in Lebanon with Y-chromosome haplogroups that are informative of the disease origin and its exclusivity to the Muslim community. A total of 732 samples were analyzed, including 33 SCD patients from Lebanon genotyped for 28 binary markers and 19 short tandem repeats on the non-recombinant segment of the Y chromosome. Genetic organization was identified using populations known to have influenced the genetic structure of the Lebanese population, in addition to African populations with high incidence of SCD. Y-chromosome haplogroup R-M343 sub-lineages distinguish between sub-Saharan African and Lebanese Y chromosomes. We detected a limited penetration of SCD into Lebanese R-M343 carriers, restricted to Lebanese Muslims. We suggest that this penetration brought the sickle cell gene along with the African R-M343, probably with the Saharan caravan slave trade.     

βA globin gene haplotypes in Mexican Huichols: Genetic relatedness to other populations

The haplotypes of 97 β^A independent chromosomes from a Mexican Huichol Native American group were analyzed. The analysis also included 87 β^A chromosomes from a Mexican Mestizo population previously studied. Among Huichols, eight different 5′ β haplotypes (5Hps) were observed, with types 1(+ − − − −), 13(+ + + − +) and 2(− + + − +) at frequencies of 0.794, 0.093, and 0.041, respectively. In Mestizos, 17 5Hps were found, types 1, 3(− + − + +), 2, 5(− + − − +) and 9(− − − − −) being the most common at frequencies of 0.391, 0.172, 0.092, 0.069, and 0.046, respectively. 3′ haplotype (3Hps) frequency distributions were 0.443(+ +), 0.083(+ −), and 0.474(− +) in Huichols and 0.563(+ +), 0.149(+ −), and 0.287(− +) in Mestizos. Pairwise comparison for both haplotype distributions between the two populations showed significant differences. Pairwise distributions of 3Hps for Huichols were compared with nine worldwide populations, three African, two Asian, two Melanesian, one Caucasian, and one United States Native American. The distributions of the Huichol were different (P < 0.05) from all populations except the Native American. Nei's genetic distances showed the Huichols to be closer to the Native Americans, followed by Melanesians from Vanuatu and Asians; Africans were the farthest. The 5Hp distributions in Mexicans were also compared with 23 worldwide populations (including African, Native American, Asian, Caucasian, and Pacific Islanders). Huichol distributions were different (P < 0.05) from all other populations except Koreans. The Mestizo distribution was also different from the others, except three Caucasian groups. Nei's genetic distance between the same populations disclosed that the Huichols are in relatively close proximity to five out of six Asian populations considered. The same analysis with grouped worldwide populations showed Native Americans as population closest to the Huichols, followed by Pacific Islanders and Asians. Present observations are consistent with an important Asian contribution to the Huichol genome in this chromosomal region. Am. J. Hum. Biol. 12:201–206, 2000. © 2000 Wiley-Liss, Inc.     

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.     

Frequency of HLA-DQB*06 in Caucasian,African American, and Mexican American patients with a positive direct antiglobulin test

A reduced frequency of HLA-DQ6 in patients with a positive direct antiglobulin test (DAT) was previously reported but race was undisclosed. Therefore, we investigated a total of 275 patients (80 Caucasian, 113 African American, and 82 Mexican American) and 518 normal controls (205 Caucasian, 208 African American, and 105 Mexican American). These were typed for class II HLA antigens using molecular techniques. A DAT was performed on each patient's red cells drawn into EDTA using both mouse and rabbit polyspecific reagents. Of 275 patients tested, 73 (27%) had a positive DAT (12 Caucasians, 35 African Americans, and 26 Mexican Americans). We found that 5 (42%) Caucasian patients and 103 (50%) Caucasian controls possessed the DQB*06 allele (p =.56). In the African American group, 15 (43%) patients and 91 controls (44%) were DQB*06 positive (p =.92). Six Mexican American patients (23%) and 21 controls (20%) had the DQB*06 allele (p =.72). This article underscores the need to use race-matched controls when genetic disease associations are sought.     

Assessing individual interethnic admixture and population substructure using a 48–insertion‐deletion (INSEL) ancestry‐informative marker (AIM) panel

Estimating the proportions of different ancestries in admixed populations is very important in population genetics studies, and it is particularly important for detecting population substructure effects in case‐control association studies. In this work, a set of 48 ancestry‐informative insertion‐deletion polymorphisms (INDELs) were selected with the goal of efficiently measuring the proportions of three different ancestries (sub‐Saharan African, European, and Native American) in mixed populations. All selected markers can be easily analyzed via multiplex PCR and detected with standard capillary electrophoresis. A total of 593 unrelated individuals representative of European, African, and Native American parental populations were typed, as were 380 individuals from three Brazilian populations with known admixture patterns. As expected, the interethnic admixture estimates show that individuals from southern Brazil present an almost exclusively European ancestry; Afro‐descendant communities in the Amazon region, apart from the major African contribution, present some degree of admixture with Europeans and Native Americans; and a sample from Belém, in the northeastern Amazon, shows a significant contribution of the three ethnic groups, although with a greater European proportion. In summary, a panel of ancestry‐informative INDELs was optimized and proven to be a valuable tool for estimating individual and global ancestry proportions in admixed populations. The ability to accurately infer interethnic admixtures highlights the usefulness of this marker set for assessing population substructure in association studies, particularly those conducted in Brazilian and other Latin American populations sharing trihybrid ancestry patterns. Hum Mutat 31:184–190, 2010. © 2009 Wiley‐Liss, Inc.     

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.     

Y-chromosome haplogroup diversity in the sub-Himalayan Terai and Duars populations of East India

The sub-Himalayan Terai and Duars, the important outermost zones comprising the plains of East India, are known as the reservoirs of ethnic diversity. Analysis of the paternal genetic diversity of the populations inhabiting these regions and their genetic relationships with adjacent Himalayan and other Asian populations has not been addressed empirically. In the present investigation, we undertook a Y-chromosome phylogeographic study on 10 populations (n=375) representing four different linguistic groups from the sub-Himalayan Terai and Duars regions of East India. The high-resolution analysis of Y-chromosome haplogroup variations based on 76 binary markers revealed that the sub-Himalayan paternal gene pool is extremely heterogeneous. Three major haplogroups, namely H, O and R, are shared across the four linguistic groups. The Indo-European-speaking castes exhibit more haplogroup diversity than the tribal groups. The findings of the present investigation suggest that the sub-Himalayan gene pools have received predominant Southeast Asian contribution. In addition, the presence of Northeast and South Asian signatures illustrate multiple events of population migrations as well as extensive genetic admixture amongst the linguistic groups.     

Admixture estimates based on ABO, Rh and nine STRs in two Venezuelan regions

BACKGROUND: The Venezuelan population is the product of Native American, African and European admixture. Few admixture studies have been made in Venezuela using short tandem repeats (STRs). AIM: The study estimated the contribution of each parental group in two Venezuelan regions: the Northern-Central and the Central-Western Regions. SUBJECTS AND METHODS: Frequencies for ABO and Rh were estimated by maximum likelihood, and by direct count for nine STRs, for 211 individuals. Admixture was estimated using Chakraborty's gene identity method. Neighbour-joining dendrograms were obtained with Nei's DS distance calculated between the two regions, the parental populations and other Venezuelan and Latin American populations. A principal component analysis (PCA) was also performed. RESULTS: For the Northern-Central Region, the estimate of admixture was 37.7% for the European component, 37.7% for the African and 24.6% for the Native American. For the Central-Western region, the estimate of admixture was 58.5% for the European, 16.5% for the African and 25.0% for the Native American component. CONCLUSIONS: (i) All systems were in Hardy-Weinberg equilibrium, except the Rh blood group of the Central-Western Region; (ii) the European contribution is high in both groups; (iii) in the dendrogram and PCA, the studied populations appear close to other admixed populations, and their relative position with regard to the three parental populations coincides with the admixture analysis.     

TNF-alpha, TGF-beta, IL-10, IL-6, and INF-gamma alleles among African Americans and Cuban Americans. Report of the ASHI Minority Workshops: Part IV

Point mutations or single nucleotide substitutions in the regulatory regions of cytokine genes may affect levels of cytokine expression and have been associated with acute and chronic rejection in organ transplantation, severity of graft-versus-host disease in hematopoietic stem cell transplants, and predisposition to autoimmune disorders. Because these cytokine variants have been studied primarily among Caucasians, we defined the alleles and frequencies of five cytokines among 691 unrelated, adult African Americans and 296 Cuban Americans in the American Society for Histocompatibility/National Institutes of Health Minority HLA Workshops. The genotypes of all cytokines, except for transforming growth factor (TGF)-beta among African Americans, were found to be in Hardy-Weinberg's equilibrium. Genotype frequencies among African American and Cuban American participants were compared with those of 75 North American Caucasian bone marrow donors and with published frequencies. Significant differences were observed in all comparisons except between Cuban and Caucasian Americans for alleles of interferon (IFN)-gamma, interleukin (IL)-6, and IL-10. The most notable differences were in genotype frequencies of African Americans compared with those of the two other populations. The frequency of the IFN-gamma genotype A/A, which is associated with low expression, was significantly higher in African Americans than in Caucasian or Cuban Americans (0.66 vs 0.37 and 0.26, respectively; p < 0.0001 for both comparisons). The high-expression G/G genotype for IL-6 was more than twice as prevalent among African Americans as among Caucasians and 1.5 times more frequent than among Cuban Americans (respective frequencies: 0.85 vs 0.38 and 0.49; p < 0.0001 for both comparisons). In African Americans, the frequency of the high-expression genotype for IL-10, GCC/GCC, was approximately half that of the frequency in Cuban and Caucasian Americans (0.10 vs 0.19 and 0.23, respectively; p < 0.0001, p = 0.004). Because levels of expression can affect inflammation and immune regulation, differences in cytokine allele frequencies between racial or ethnic groups may contribute to different incidences of autoimmunity and allograft rejection.