Amerindian Ancestry Research Articles

Haplotype Study in SCA10 Families Provides Further Evidence for a Common Ancestral Origin of the Mutation

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disorder characterized by progressive cerebellar ataxia and epilepsy. The disease is caused by a pentanucleotide ATTCT expansion in intron 9 of the ATXN10 gene on chromosome 22q13.3. SCA10 has shown a geographical distribution throughout America with a likely degree of Amerindian ancestry from different countries so far. Currently available data suggest that SCA10 mutation might have spread out early during the peopling of the Americas. However, the ancestral origin of SCA10 mutation remains under speculation. Samples of SCA10 patients from two Latin American countries were analysed, being 16 families from Brazil (29 patients) and 21 families from Peru (27 patients) as well as 49 healthy individuals from Indigenous Quechua population and 51 healthy Brazilian individuals. Four polymorphic markers spanning a region of 5.2cM harbouring the ATTCT expansion were used to define the haplotypes, which were genotyped by different approaches. Our data have shown that 19-CGGC-14 shared haplotype was found in 47% of Brazilian and in 63% of Peruvian families. Frequencies from both groups are not statistically different from Quechua controls (57%), but they are statistically different from Brazilian controls (12%) (p<0.001). The most frequentexpanded haplotype in Quechuas, 19-15-CGGC-14-10, is found in 50% of Brazilian and in 65% of Peruvian patients with SCA10. These findings bring valuable evidence that ATTCT expansion may have arisen in a Native American chromosome.

Amerindian ancestry and extended longevity in Nicoya, Costa Rica.

The aim of this study was to address the hypothesis that Amerindian ancestry is associated with extended longevity in the admixed population of Nicoya, Costa Rica. The Nicoya Peninsula of Costa Rica has been considered a "longevity island," particularly for males. We estimated Amerindian ancestry using 464 ancestral informative markers in 20 old Nicoyans aged ≥99 years, and 20 younger Nicoyans (60-65 years). We used logistic regression to estimate odds ratio (OR) and 95% confidence interval (CI) of the association of Amerindian ancestry and longevity. Older Nicoyans had higher Amerindian ancestry compared to younger Nicoyans (43.3% vs 36.0%, P = .04). Each 10% increase of Amerindian ancestry was associated with more than twice the odds of being long-lived (OR = 2.32, 95% CI = 1.03-5.25). To our knowledge, this is the first time that ancestry is implicated as a likely determinant of extended longevity. Amerindian-specific alleles may protect against early mortality. The identification of these protective alleles should be the focus of future studies.

P198 Allele diversity at six HLA LOCI: A∗, B∗, C∗, DRB1∗, DQB1∗ and DPB1∗, in two regions of mexico determined by sequence based typing (SBT) and next generation sequencing (NGS); the highlands and the South-East

Aim In outbred populations such as Mexican Mestizos, the allele frequencies are fairly evenly distributed in most HLA loci with the exception of DPB1, in which only a few alleles account for the majority of the genes; this results in low levels of homozygosity, again, with the exception of DPB1, suggesting overdominant selection. The aim was to compare the HLA distribution and significance of variation in Mestizos form the Highlands vs. those from Oaxaca, emphasizing that the ancestry is more Mediterranean in the former, prevailing in Oaxaca the Amerindian and African ancestries. Methods We selected 103 Mestizos from the Highlands/Center, being 58.2% females and 41.8% males with an X age = 37.7y. HLA A∗,B∗,C∗, DRB1∗,DQB1∗,DPB1, DNA genotyping was done by SBT on a 3500 ABI instrument. Allele frequency (AF) was calculated with the SPSS17 software; the haplotype (HF) analysis was assessed with the Arlequin 3.5.1.2 using the maximum likelihood method. Data were compared with those previously shown by NGS for 11 loci of 197 subjects from Oaxaca. Results The prevalent alleles >5%: were: A∗02:01, ∗02∗06, ∗24:02, ∗01:01, ∗11:01; B∗39:05, ∗35:01, ∗14:02, ∗18:01, ∗51:01;C∗04:01, ∗07:02, ∗01:02, ∗07:01, ∗12:03, ∗03:04, ∗05:01;DRB1∗04:07, ∗08:02, ∗04:04, ∗03:01, ∗01:02, ∗07:01; DQB1∗03:02, ∗04:02, ∗03:01, ∗05:01;DPB1∗04:02, ∗02: 01, ∗04:01, ∗11:01. In Oaxaca however, the most frequent variants are: A∗02:01, ∗24:02, ∗02:06, ∗31:01, ∗68:01, ∗68:03, ∗02:05;B∗39:01, ∗35:01, ∗08:01, ∗51:01, ∗45:01; C∗07:02, ∗04:01, ∗01:02, ∗03:03; DRB1∗04:07, ∗08:02, ∗16:02, ∗03:01, ∗11:04, ∗14:06; DQB1∗03:02, ∗04:02, ∗03:01; ∗02:01; DPB1∗04:02, ∗02:01, ∗04:01, ∗03:01. Conclusions Great diversity exists in both groups, with a higher Mediterranean allele content in the highlands; the top 5 haplotypes found in here, are also shown in Sephardi Jews, Spanish and Lebanese. Three haplotypes are unique to Mexican Natives. Among the 10 main haplotypes present in Oaxaca, 5 exist in the Middle-East and in Sephardi Jews and 5 are unique to Mexican Natives, especially in those form Southern Mexico. In these populations, any novel allele may have been positively selected to enlarge the peptide-binding repertoire, and some are found with distinctive haplotype associations, suggesting that convergent evolution events may have also taken place.

Analysis of ancestry informative markers in three main ethnic groups from Ecuador supports a trihybrid origin of Ecuadorians

Ancestry inference is traditionally done using autosomal SNPs that present great allele frequency differences among populations from different geographic regions. These ancestry informative markers (AIMs) are useful for determining the most likely biogeographic ancestry or population of origin of an individual. Due to the growing interest in AIMs and their applicability in different fields, commercial companies have started to develop AIM multiplexes targeted for Massive Parallel Sequencing platforms.This project focused on the study of three main ethnic groups from Ecuador (Kichwa, Mestizo, and Afro-Ecuadorian) using the Precision ID Ancestry panel (Thermo Fisher Scientific). In total, 162 Ecuadorian individuals were investigated. The Afro-Ecuadorian and Mestizo showed higher average genetic diversities compared to the Kichwa. These results are consistent with the highly admixed nature of the first two groups. The Kichwa showed the highest proportion of Native Amerindian (NAM) ancestry relative to the other two groups. The Mestizo had an admixed ancestry of NAM and European with a larger European component, whereas the Afro-Ecuadorian were highly admixed presenting proportions of African, Native Amerindian, and European ancestries. The comparison of our results with previous studies based on uniparental markers (i.e. Y chromosome and mtDNA) highlighted the sex-biased admixture process in the Ecuadorian Mestizo.Overall, the data generated in this work represent one important step to assess the application of ancestry inference in admixed populations in a forensic context.

MtDNA structure: the women who formed the Brazilian Northeast

BackgroundThe distribution of mitochondrial DNA (mtDNA) lineages in Brazil is heterogeneous due to different regional colonization dynamics. Northeastern Brazil, although being an important region in terms of human imigration and ethnic admixture, has little information regarding its population mtDNA composition. Here, we determine which mitochondrial lineages contributed to the formation of the Northeastern Brazilian population. Our sample consisted of 767 individuals distributed as follows i) 550 individuals from eight Northeastern states (Piauí, Ceará, Rio Grande do Norte, Paraíba, Pernambuco, Alagoas, Sergipe, and Bahia) which were sequenced for mtDNA hypervariable segments I, II, and III; ii) 217 individuals from Alagoas and Pernambuco (previously published data). Data analysis was performed through sequence alignment and Haplogrep 2.0 haplogroup assignment tools. Furthermore, maternal ancestry distribution was contextualized and, when possible, related to historical events to better understand the biological interactions and population dynamics that occurred in this region since the beginning of colonization.ResultsUnexpectedly, Amerindian mitochondrial ancestry was the highest in the Northeastern region overall, followed by African, European and non-Amerindian Asian, unlike previous results for this region. Alagoas and Pernambuco states, however, showed a larger African mtDNA frequency. The Northeastern region showed an intraregional heterogeneous distribution regarding ancestral groups, in which states/mesoregions located to the north had a prevalent Amerindian ancestral frequency and those to the south had predominance of African ancestry. Moreover, results showed great diversity of European haplogroups and the presence of non-Amerindian Asian haplogroups.ConclusionsOur findings are in disagreement with previous investigations that suggest African mitochondrial ancestry is the most prevalent in the Brazilian Northeast. The predominance of Amerindian lineages exemplifies the importance of indigenous women in the formation of the population, despite intense African slave entry and conflicts with European settlers. The variable distribution of ancestral groups observed in the Northeast is in accordance with historical records showing the similarities with colonization dynamics occurred in the Amazon region and the Brazilian Southeast. Moreover, the variety of European haplogroups suggests multiple origins of founding groups, specially those found in Western European populations.

Transancestral mapping and genetic load in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P<5 × 10−8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.

Ancestry dynamics in a South American population: The impact of gene flow and preferential mating.

European ancestry in many populations in Latin America at autosomal loci is often higher than that from X-linked loci indicating more European male ancestry and more Amerindian female ancestry. Generally, this has been attributed to more European male gene flow but could also result from an advantage to European mating or reproductive success. Population genetic models were developed to investigate the dynamics of gene flow and mating or reproductive success. Using estimates of autosomal and X-chromosome European ancestry, the amount of male gene flow or mating or reproductive advantage for Europeans, or those with European ancestry, was estimated. In a population from Antioquia, Colombia with an estimated 79% European autosomal ancestry and an estimated 69% European X-chromosome ancestry, about 15% male gene flow from Europe or about 20% mating or reproductive advantage of Europeans over Amerindians resulted in these levels of European ancestry in the contemporary population. Combinations of gene flow and mating advantage were nearly additive in their impact. Gene flow, mating advantage, or a combination of both factors, are consistent with observed levels of European ancestry in a Latin American population. This approach provides a general methodology to determine the levels of gene flow and mating differences that can explain the observed contemporary differences in ancestry from autosomes and X-chromosomes.

Genome-wide association of white blood cell counts in Hispanic/Latino Americans: the Hispanic Community Health Study/Study of Latinos.

Circulating white blood cell (WBC) counts (neutrophils, monocytes, lymphocytes, eosinophils, basophils) differ by ethnicity. The genetic factors underlying basal WBC traits in Hispanics/Latinos are unknown. We performed a genome-wide association study of total WBC and differential counts in a large, ethnically diverse US population sample of Hispanics/Latinos ascertained by the Hispanic Community Health Study and Study of Latinos (HCHS/SOL). We demonstrate that several previously known WBC-associated genetic loci (e.g. the African Duffy antigen receptor for chemokines null variant for neutrophil count) are generalizable to WBC traits in Hispanics/Latinos. We identified and replicated common and rare germ-line variants at FLT3 (a gene often somatically mutated in leukemia) associated with monocyte count. The common FLT3 variant rs76428106 has a large allele frequency differential between African and non-African populations. We also identified several novel genetic loci involving or regulating hematopoietic transcription factors (CEBPE-SLC7A7, CEBPA and CRBN-TRNT1) associated with basophil count. The minor allele of the CEBPE variant associated with lower basophil count has been previously associated with Amerindian ancestry and higher risk of acute lymphoblastic leukemia in Hispanics. Together, these data suggest that germline genetic variation affecting transcriptional and signaling pathways that underlie WBC development and lineage specification can contribute to inter-individual as well as ethnic differences in peripheral blood cell counts (normal hematopoiesis) in addition to susceptibility to leukemia (malignant hematopoiesis).

Admixture Mapping Identifies an Amerindian Ancestry Locus Associated with Albuminuria in Hispanics in the United States.

Increased urine albumin excretion is highly prevalent in Hispanics/Latinos. Previous studies have found an association between urine albumin excretion and Amerindian ancestry in Hispanic/Latino populations. Admixture between racial/ethnic groups creates long-range linkage disequilibrium between variants with different allelic frequencies in the founding populations and it can be used to localize genes. Hispanic/Latino genomes are an admixture of European, African, and Amerindian ancestries. We leveraged this admixture to identify associations between urine albumin excretion (urine albumin-to-creatinine ratio [UACR]) and genomic regions harboring variants with highly differentiated allele frequencies among the ancestral populations. Admixture mapping analysis of 12,212 Hispanic Community Health Study/Study of Latinos participants, using a linear mixed model, identified three novel genome-wide significant signals on chromosomes 2, 11, and 16. The admixture mapping signal identified on chromosome 2, spanning q11.2-14.1 and not previously reported for UACR, is driven by a difference between Amerindian ancestry and the other two ancestries (P<5.7 × 10-5). Within this locus, two common variants located at the proapoptotic BCL2L11 gene associated with UACR: rs116907128 (allele frequency =0.14; P=1.5 × 10-7) and rs586283 (C allele frequency =0.35; P=4.2 × 10-7). In a secondary analysis, rs116907128 accounted for most of the admixture mapping signal observed in the region. The rs116907128 variant is common among full-heritage Pima Indians (A allele frequency =0.54) but is monomorphic in the 1000 Genomes European and African populations. In a replication analysis using a sample of full-heritage Pima Indians, rs116907128 significantly associated with UACR (P=0.01; n=1568). Our findings provide evidence for the presence of Amerindian-specific variants influencing the variation of urine albumin excretion in Hispanics/Latinos.

Genome-Wide Analysis in Brazilians Reveals Highly Differentiated Native American Genome Regions.

Despite its population, geographic size, and emerging economic importance, disproportionately little genome-scale research exists into genetic factors that predispose Brazilians to disease, or the population genetics of risk. After identification of suitable proxy populations and careful analysis of tri-continental admixture in 1,538 North-Eastern Brazilians to estimate individual ancestry and ancestral allele frequencies, we computed 400,000 genome-wide locus-specific branch length (LSBL) Fst statistics of Brazilian Amerindian ancestry compared to European and African; and a similar set of differentiation statistics for their Amerindian component compared with the closest Asian 1000 Genomes population (surprisingly, Bengalis in Bangladesh). After ranking SNPs by these statistics, we identified the top 10 highly differentiated SNPs in five genome regions in the LSBL tests of Brazilian Amerindian ancestry compared to European and African; and the top 10 SNPs in eight regions comparing their Amerindian component to the closest Asian 1000 Genomes population. We found SNPs within or proximal to the genes CIITA (rs6498115), SMC6 (rs1834619), and KLHL29 (rs2288697) were most differentiated in the Amerindian-specific branch, while SNPs in the genes ADAMTS9 (rs7631391), DOCK2 (rs77594147), SLC28A1 (rs28649017), ARHGAP5 (rs7151991), and CIITA (rs45601437) were most highly differentiated in the Asian comparison. These genes are known to influence immune function, metabolic and anthropometry traits, and embryonic development. These analyses have identified candidate genes for selection within Amerindian ancestry, and by comparison of the two analyses, those for which the differentiation may have arisen during the migration from Asia to the Americas.

Amerindian (but not African or European) ancestry is significantly associated with diurnal preference within an admixed Brazilian population

ABSTRACTSignificant questions remain unanswered regarding the genetic versus environmental contributions to racial/ethnic differences in sleep and circadian rhythms. We addressed this question by investigating the association between diurnal preference, using the morningness–eveningness questionnaire (MEQ), and genetic ancestry within the Baependi Heart Study cohort, a highly admixed Brazilian population based in a rural town. Analysis was performed using measures of ancestry, using the Admixture program, and MEQ from 1,453 individuals. We found an association between the degree of Amerindian (but not European of African) ancestry and morningness, equating to 0.16 units for each additional percent of Amerindian ancestry, after adjustment for age, sex, education, and residential zone. To our knowledge, this is the first published report identifying an association between genetic ancestry and MEQ, and above all, the first one based on ancestral contributions within individuals living in the same community. This previously unknown ancestral dimension of diurnal preference suggests a stratification between racial/ethnic groups in an as yet unknown number of genetic polymorphisms.

Effect of ancestry on interleukin-10 haplotypes in chronic periodontitis.

Chronic periodontitis is caused by an inflammatory reaction of the periodontal tissues and alveolar bone. This inflammation is caused by periodontopathic bacteria located in the subgingival biofilm, resulting in inflammatory reactions that may lead to loss of attachment. This tissue destruction is a consequence of host immune and inflammatory responses to specific periodontal pathogens and their metabolic products. Cytokines modulate the immune response, altering its efficiency in the competition against pathogens and increasing periodontal susceptibility. This study investigated genetic polymorphisms in Interleukin 10 (A-1082G, C-819T and C-592A) in 205 individuals from an admixed Brazilian population. A significantly increased risk of developing chronic periodontitis was observed in individuals with low IL-10 production and Amerindian ancestry. These results suggest that the polymorphisms A-1082G, C-819T, and C-592A, which are associated with ancestry, are involved in the susceptibility to the development of chronic periodontitis in an admixed northern Brazilian population.

The targetable A1 Huntington disease haplotype has distinct Amerindian and European origins in Latin America.

Huntington disease (HD) is a dominant neurodegenerative disorder caused by a CAG repeat expansion in the Huntingtin (HTT) gene. HD occurs worldwide, but the causative mutation is found on different HTT haplotypes in distinct ethnic groups. In Latin America, HD is thought to have European origins, but indigenous Amerindian ancestry has not been investigated. Here, we report dense HTT haplotypes in 62 mestizo Peruvian HD families, 17 HD families from across Latin America, and 42 controls of defined Peruvian Amerindian ethnicity to determine the origin of HD in populations of admixed Amerindian and European descent. HD in Peru occurs most frequently on the A1 HTT haplotype (73%), as in Europe, but on an unexpected indigenous variant also found in Amerindian controls. This Amerindian A1 HTT haplotype predominates over the European A1 variant among geographically disparate Latin American controls and in HD families from across Latin America, supporting an indigenous origin of the HD mutation in mestizo American populations. We also show that a proportion of HD mutations in Peru occur on a C1 HTT haplotype of putative Amerindian origin (14%). The majority of HD mutations in Latin America may therefore occur on haplotypes of Amerindian ancestry rather than on haplotypes resulting from European admixture. Despite the distinct ethnic ancestry of Amerindian and European A1 HTT, alleles on the parent A1 HTT haplotype allow for development of identical antisense molecules to selectively silence the HD mutation in the greatest proportion of patients in both Latin American and European populations.

Amerindian/Asian Ancestry and Mortality Are Associated with Allo-Immunization in Adults with Sickle Cell Disease in a Genome Wide Racial Admixture Study

▪Background: Transfusion is a standard therapy for acute and chronic complications of sickle cell disease (SCD). They are complicated by a high prevalence of red cell antigen alloimmunization, which is not seen in other frequently transfused patients. Reasons for this increased prevalence are unclear. Some studies have suggested genetic predisposition to alloimmunization in all transfused patient populations. Others suggested that mismatched red cell antigens occurring commonly between blood donors of European ancestry and patients with SCD who are of African ancestry is a primary cause in SCD. Accordingly, phenotypic antigen matching and transfusion from African American donors are proposed strategies to minimize alloimmunization risk. We hypothesized that if these population differences are the etiologic basis that analysis of ancestry at the genetic level could identify significant genetic susceptibility contributions and localize susceptibility loci.Methods: The Bethesda Sickle Cell Cohort Study consisting of adults evaluated at NIH from 2001-2015 (n=721) was reviewed for transfusion history and the presence of allo-antibodies confirmed with a blood bank. Genomic DNA was genotyped with an admixture panel consisting of 2251 ancestry informative SNPs in 359 patients and in HapMap controls. A final panel of 1622 SNPs was used to infer ancestry proportions using Structure assuming 3 ancestral populations. Ancestry was analyzed in regression models along with clinical variables. Genome wide admixture mapping was performed to identify regions of the genome where the ancestry proportions differed significantly between cases and controls. We used AncestryMap for a log-additive case control study assuming various risk models.Results: Five hundred fifty four subjects (77% of cohort) had a transfusion history with 153 (27.6 %) with allo-antibodies, 336 (60.6 %) with a history of transfusions and no antibodies and 65 (11.7 %) with no prior transfusions. Sixty five percent had a history of more than 1 antibody. The RH, Kell, MNS and Duffy systems were most commonly associated with antibodies (Fig 1A and B). Clinical factors associated with cases in univariate analysis included transfusion burden (P<0.0001), pain hospitalizations (P=0.0007), hemoglobin (P=0.02), ferritin (P=0.002), alkaline phosphatase (P=0.02) and ESR (P=0.05). Only transfusion history remained significant in multivariable models, both when using logistic (antibody status, β=0.56, P=6.31 x 10-6) or linear (number of antibodies, β=0.35, P=0.0004) regressions. Given the univariate associations with pain hospitalizations and ferritin which are known mortality risk factors, it was not surprising that allo-immunization was associated with mortality when compared to the no antibody and non-transfusion groups (Fig 1C; median follow-up 3.8 years, range 0-14.4). The absence of allo-immunization showed decreased risk of death when limited to only those with prior transfusions (Fig 1D; Hazard Ratio 0.53, P=0.006). When considering genotype data, Asian/Amerindian ancestry was associated with antibody status (logistic, β=4.60, P=0.03) and number of antibodies (linear, β=4.92, P=0.006) by regression, while African and European ancestry were not. The relative ancestry contribution remained unchanged when the number of prior transfusions was also included in both models, P=0.09 and P=0.06, respectively (Fig 1E). Genetic data also indicated that 21% (n=77) of genotyped subjects were not admixed (100% African ancestry) which violates AncestryMap’s assumption that all subjects are admixed. These subjects were removed from the admixture scan: an analysis of 81 cases and 159 controls with prior transfusions is underway to identify specific susceptibility loci.Conclusions: In a large cohort of adults with SCD, the prevalence of red cell alloimmunization is 27.6%, with approximately 60% of antibodies attributable to RH and Kell. Asian/Amerindian ancestry is a risk factor, as is the number of prior transfusions. This study demonstrates genetic susceptibility to this complication which is associated with an ancestral population not typically considered in SCD. Identification of additional Amerindian ancestry SNPs will help to fine map susceptibility loci. Long term studies will be necessary to determine the relative contribution of alloimmunization to mortality in adults with SCD. [Display omitted] DisclosuresKato:Mast Therapeutics: Consultancy; Bayer: Research Funding.

P111 Five locus high resolution extended haplotypes (eh) in healthy Mexican mestizos from the Highlands of Mexico

Aim Continental ancestries are better represented by autosome gene frequencies, such as those of the MHC. In Mexico, Amerindian ancestry is prevalent (51–56%), followed by European (40–45%); the African share being 2–5%, depending on the area. Generation and maintenance of EH has several explanations: it may have been driven to high frequency, over a short period of time by positive selection, or conserved segments are exposed to allele specific recombination suppression, preventing haplotype breakdown. The aim of the study was to sequence a group of Mexican admixed healthy subjects, to determine the EH from unrelated and from family members of certain geographic areas. Methods HLA A ∗ ,C ∗ ,B ∗ ,DRB1 ∗ ,DQB1 ∗ genotyping was performed in 116 Mestizo unrelated controls, 66.4% of the Highlands, Center or North Mexico and 52 (73.1%) family members. DNA was extracted using the Maxwell16 and were sequenced on a 3500 ABI instrument. Allele frequencies (AF) were calculated with the SPSS 12 software and the haplotype (HF) analyses of the unrelated individuals was done with the Arlequin 3.5.1.2 software using the maximum likelihood method. The HF from families was calculated by direct counting. Results The 2 prevalent EH were typically Mexican: A ∗ 02:06-C ∗ 07:02-B ∗ 39:05-DRB1 ∗ 04:07-DQB1 ∗ 03:02, A ∗ 02:01-C ∗ 04:01-B ∗ 35:12-DRB1 ∗ 08:02-DQB1 ∗ 04:02 while the 4th was the cEH A ∗ 01:01-C ∗ 07:01-B ∗ 08:01-DRB1 ∗ 03:01-DQB1 ∗ 02:01. Other ethnic influences and the biological and significance are further discussed. Conclusions Asian EH, from NE China: 11:01-12:02-52:01-15:02:-06:01; Lebanese: 33:01-08:02-14:02-01:02-05:01 and African Bantu, 01:01-12:02-52:01-15:02-06:01, were observed. Some alleles have identical protein sequences but are distinguished at the DNA level by silent substitutions, and many alleles/haplotypes were particular of Mexicans: variants of B39 and B35 like: ∗ 39:05, 39:06, 35:12, 35:14, 35:16, 35:08,35:17, 35:03, 35:28 and 35:17, all of them in distinct EH: these alleles may be ancient or derived from founder ones by gene conversion events. This is true for B locus and it probably happened because the new alleles provided selective advantages, enlarging the peptide binding repertoire of the population, to be able to deal with the particular ecological niche.

Analysis of cytokine gene polymorphisms in Mestizo and native populations from Mexico.

To determine whether the well-known genetic structure of the Mexican population observed with other multiallelic markers can be detected by analyzing functional polymorphisms of cytokine and other inflammatory-response-related genes. A total of 834 Mestizo individuals from five Mexican cities and 92 Lacandonians - an Amerindian group from southeastern Mexico - were genotyped for 14 polymorphisms in the CRP, IL10, IL6, TGFB1, TNFA, LTA, ICAM1 IFNG, and IL1RN genes. Allele and haplotype frequencies were used for genetic structure analysis using F-statistics pairwise distances and multidimensional scaling plot. Ancestry analysis was performed, as well. Significant interpopulational differences at the allele and haplotype frequency level were observed, mainly between Northern (Guadalajara, Monterrey, and Culiacan) and Southern (Tierra Blanca and Puebla) Mexican populations. Also, low but significant substructure was detected between some populations from these two broad regions. Interestingly, both Lacandonian populations were highly differentiated from each other and with respect to Mestizos. Consistent with previous data, Amerindian ancestry in the Southern Mexican groups was higher compared to Northern ones. The Mexican population exhibits regional differences in functional polymorphisms of inflammatory-response genes, as observed for other genetic markers. This information constitutes a reference for epidemiological studies that include these genetic markers to assess the susceptibility of the Mexican population to several immune-response-related diseases, such as diabetes, obesity, and renal disease, which have been shown to be common in the Mexican population but with prevalence differences within this country.

Genomic ancestry as a predictor of haemodynamic profile in heart failure

ObjectiveThe aim of this study is to assess the association between genetic ancestry, self-declared race and haemodynamic parameters in patients with chronic heart failure (HF).MethodsObservational, cross-sectional study. Eligible participants were...

Local Ancestry Inference in a Large US-Based Hispanic/Latino Study: Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

We estimated local ancestry on the autosomes and X chromosome in a large US-based study of 12,793 Hispanic/Latino individuals using the RFMix method, and we compared different reference panels and approaches to local ancestry estimation on the X chromosome by means of Mendelian inconsistency rates as a proxy for accuracy. We developed a novel and straightforward approach to performing ancestry-specific PCA after finding artifactual behavior in the results from an existing approach. Using the ancestry-specific PCA, we found significant population structure within African, European, and Amerindian ancestries in the Hispanic/Latino individuals in our study. In the African ancestral component of the admixed individuals, individuals whose grandparents were from Central America clustered separately from individuals whose grandparents were from the Caribbean, and also from reference Yoruba and Mandenka West African individuals. In the European component, individuals whose grandparents were from Puerto Rico diverged partially from other background groups. In the Amerindian ancestral component, individuals clustered into multiple different groups depending on the grandparental country of origin. Therefore, local ancestry estimation provides further insight into the complex genetic structure of US Hispanic/Latino populations, which must be properly accounted for in genotype-phenotype association studies. It also provides a basis for admixture mapping and ancestry-specific allele frequency estimation, which are useful in the identification of risk factors for disease.

Killer cell immunoglobulin-like receptor and human leukocyte antigen gene profiles in a cohort of HIV-infected Mexican Mestizos.

Killer cell immunoglobulin-like receptors (KIRs) represent the most polymorphic genes responsible for natural killer cell function, while human leukocyte antigen (HLA) class I molecules define and restrict cytotoxic T lymphocyte responses. Specific KIR, HLA, or KIR-HLA combinations have been implicated in the outcome of human immunodeficiency virus (HIV) disease. The remarkable polymorphism of KIR and HLA genes warrants descriptive gene frequency studies in different populations, as well as their impact on HIV disease progression in different immunogenetic contexts. We report KIR and HLA class I gene profiles of 511 unrelated HIV-infected Mexican Mestizo individuals from 18 states for whom genetic ancestry proportions were assessed. KIR and HLA gene profiles were compared between individuals from the north and central-south regions of the country and between individuals with higher European (EUR) or Amerindian (AMI) genetic ancestry component. A total of 65 KIR genotypes were observed, 11 harboring novel KIR gene combinations. A total of 164 HLA alleles were observed: 43 HLA-A, 87 HLA-B, and 34 HLA-C. Differences in the distribution of 12 HLA alleles were observed between individuals with higher AMI or EUR ancestry components (p<0.05, q<0.2). After correcting for genetic ancestry, only individual HLA alleles were associated with HIV disease progression, including a novel association with A*02:06, an Amerindian HLA allele associated with lower CD4+ T cell counts. No KIR effects were significant. Our results highlight the advantages of considering a detailed genetic stratification within populations when studying genetic profiles that could be implicated in disease-association studies.

Analysis of the genetic ancestry of patients with oral clefts from South American admixed populations.

Increased susceptibility to cleft lip, with or without cleft palate (CL±P) has been observed in South America, as related to Amerindian ancestry, using epidemiological data, uniparental markers, and blood groups. In this study, it was evaluated whether this increased risk remains when Amerindian ancestry is estimated using autosomal markers and considered in the predictive model. Ancestry was estimated through genotyping 62 insertion and deletion (INDEL) markers in sample sets of patients with CL±P, patients with cleft palate (CP), and controls, from Patagonia in southern Argentina and Belém in northern Brazil. The Amerindian ancestry in patients from Patagonia with CL±P was greater than in controls although it did not reach statistical significance. The European ancestry in patients with CL±P from Belém and in patients with CP from Belém and Patagonia was higher than in controls and statistically significant for patients with CP who were from Belém. This high contribution of European genetic ancestry among patients with CP who were from Belém has not been previously observed in American populations. Our results do not corroborate the currently accepted risks for CL±P and CP estimated by epidemiological studies in the North American populations and probably reflect the higher admixture found in South American ethnic groups when compared with the same ethnic groups from the North American populations.