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1.
Am J Hum Genet ; 107(2): 251-264, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32640185

RESUMO

Applying exome sequencing to populations with unique genetic architecture has the potential to reveal novel genes and variants associated with traits and diseases. We sequenced and analyzed the exomes of 6,716 individuals from a Southwestern American Indian (SWAI) population with well-characterized metabolic traits. We found that the SWAI population has distinct allelic architecture compared to populations of European and East Asian ancestry, and there were many predicted loss-of-function (pLOF) and nonsynonymous variants that were highly enriched or private in the SWAI population. We used pLOF and nonsynonymous variants in the SWAI population to evaluate gene-burden associations of candidate genes from European genome-wide association studies (GWASs) for type 2 diabetes, body mass index, and four major plasma lipids. We found 19 significant gene-burden associations for 11 genes, providing additional evidence for prioritizing candidate effector genes of GWAS signals. Interestingly, these associations were mainly driven by pLOF and nonsynonymous variants that are unique or highly enriched in the SWAI population. Particularly, we found four pLOF or nonsynonymous variants in APOB, APOE, PCSK9, and TM6SF2 that are private or enriched in the SWAI population and associated with low-density lipoprotein (LDL) cholesterol levels. Their large estimated effects on LDL cholesterol levels suggest strong impacts on protein function and potential clinical implications of these variants in cardiovascular health. In summary, our study illustrates the utility and potential of exome sequencing in genetically unique populations, such as the SWAI population, to prioritize candidate effector genes within GWAS loci and to find additional variants in known disease genes with potential clinical impact.


Assuntos
Exoma/genética , Predisposição Genética para Doença/genética , Índios Norte-Americanos/genética , Polimorfismo de Nucleotídeo Único/genética , Alelos , Índice de Massa Corporal , Feminino , Genética Populacional/métodos , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Fenótipo , Sudoeste dos Estados Unidos
4.
Mol Genet Genomics ; 295(4): 1013-1026, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32363570

RESUMO

Obesity, a risk factor for multiple diseases (e.g. diabetes, hypertension, cancers) originates through complex interactions between genes and prevailing environment (food habit and lifestyle) that varies across populations. Indians exhibit a unique obesity phenotype with high abdominal adiposity for a given body weight compared to matched white populations suggesting presence of population-specific genetic and environmental factors influencing obesity. However, Indian population-specific genetic contributors for obesity have not been explored yet. Therefore, to identify potential genetic contributors, we performed a two-staged genome-wide association study (GWAS) for body mass index (BMI), a common measure to evaluate obesity in 5973 Indian adults and the lead findings were further replicated in 1286 Indian adolescents. Our study revealed novel association of variants-rs6913677 in BAI3 gene (p = 1.08 × 10-8) and rs2078267 in SLC22A11 gene (p = 4.62 × 10-8) at GWAS significance, and of rs8100011 in ZNF45 gene (p = 1.04 × 10-7) with near GWAS significance. As genetic loci may dictate the phenotype through modulation of epigenetic processes, we overlapped genetic data of identified signals with their DNA methylation patterns in 236 Indian individuals and performed methylation quantitative trait loci (meth-QTL) analysis. Further, functional roles of discovered variants and underlying genes were speculated using publicly available gene regulatory databases (ENCODE, JASPAR, GeneHancer, GTEx). The identified variants in BAI3 and SLC22A11 genes were found to dictate methylation patterns at unique CpGs harboring critical cis-regulatory elements. Further, BAI3, SLC22A11 and ZNF45 variants were located in repressive chromatin, active enhancer, and active chromatin regions, respectively, in human subcutaneous adipose tissue in ENCODE database. Additionally, these genomic regions represented potential binding sites for key transcription factors implicated in obesity and/or metabolic disorders. Interestingly, GTEx portal identify rs8100011 as a robust cis-expression quantitative trait locus (cis-eQTL) in subcutaneous adipose tissue (p = 1.6 × 10-7), and ZNF45 gene expression in skeletal muscle of Indian subjects showed an inverse correlation with BMI indicating its possible role in obesity. In conclusion, our study discovered 3 novel population-specific functional genetic variants (rs6913677, rs2078267, rs8100011) in 2 novel (SLC22A11 and ZNF45) and 1 earlier reported gene (BAI3) for BMI in Indians. Our study decodes key genomic loci underlying obesity phenotype in Indians that may serve as prospective drug targets in future.


Assuntos
Estudo de Associação Genômica Ampla , Fatores de Transcrição Kruppel-Like/genética , Obesidade/genética , Transportadores de Ânions Orgânicos Sódio-Independentes/genética , Proteínas Repressoras/genética , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Índice de Massa Corporal , Metilação de DNA , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Índios Norte-Americanos/genética , Masculino , Obesidade/patologia , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Sequências Reguladoras de Ácido Nucleico/genética , Adulto Jovem
5.
Am J Respir Crit Care Med ; 202(7): 962-972, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32459537

RESUMO

Rationale: Puerto Ricans have the highest childhood asthma prevalence in the United States (23.6%); however, the etiology is uncertain.Objectives: In this study, we sought to uncover the genetic architecture of lung function in Puerto Rican youth with and without asthma who were recruited from the island (n = 836).Methods: We used admixture-mapping and whole-genome sequencing data to discover genomic regions associated with lung function. Functional roles of the prioritized candidate SNPs were examined with chromatin immunoprecipitation sequencing, RNA sequencing, and expression quantitative trait loci data.Measurements and Main Results: We discovered a genomic region at 1q32 that was significantly associated with a 0.12-L decrease in the lung volume of exhaled air (95% confidence interval, -0.17 to -0.07; P = 6.62 × 10-8) with each allele of African ancestry. Within this region, two SNPs were expression quantitative trait loci of TMEM9 in nasal airway epithelial cells and MROH3P in esophagus mucosa. The minor alleles of these SNPs were associated with significantly decreased lung function and decreased TMEM9 gene expression. Another admixture-mapping peak was observed on chromosome 5q35.1, indicating that each Native American ancestry allele was associated with a 0.15-L increase in lung function (95% confidence interval, 0.08-0.21; P = 5.03 × 10-6). The region-based association tests identified four suggestive windows that harbored candidate rare variants associated with lung function.Conclusions: We identified common and rare genetic variants that may play a critical role in lung function among Puerto Rican youth. We independently validated an inflammatory pathway that could potentially be used to develop more targeted treatments and interventions for patients with asthma.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Asma/genética , Cromossomos Humanos Par 1/genética , Cromossomos Humanos Par 5/genética , Volume Expiratório Forçado/genética , Índios Norte-Americanos/genética , Pulmão/fisiopatologia , Adolescente , Asma/fisiopatologia , Brônquios/citologia , Estudos de Casos e Controles , Linhagem Celular , Criança , Imunoprecipitação da Cromatina , Mapeamento Cromossômico , Mucosa Esofágica/metabolismo , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Expressão Gênica , Humanos , Desequilíbrio de Ligação , Pulmão/fisiologia , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Miócitos de Músculo Liso , Mucosa Nasal/metabolismo , Polimorfismo de Nucleotídeo Único , Porto Rico , Locos de Características Quantitativas , Análise de Sequência de RNA , Sequenciamento Completo do Genoma , Adulto Jovem
6.
Int J Mol Sci ; 21(2)2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31936053

RESUMO

In Mexico, the genetic mechanisms underlying childhood obesity are poorly known. We evaluated the effect of loci, known to be associated with childhood body mass index (BMI) in Europeans, in Mexican children from different ethnic groups. We performed linear and logistic analyses of BMI and obesity, respectively, in Mestizos and Amerindians (Seris, Yaquis and Nahuatl speakers) from Northern (n = 369) and Central Mexico (n = 8545). We used linear models to understand the effect of degree of Amerindian ancestry (AMA) and genetic risk score (GRS) on BMI z-score. Northern Mexican Mestizos showed the highest overweight-obesity prevalence (47.4%), followed by Seri (36.2%) and Central Mexican (31.5%) children. Eleven loci (SEC16B/rs543874, OLFM4/rs12429545/rs9568856, FTO/rs9939609, MC4R/rs6567160, GNPDA2/rs13130484, FAIM2/rs7132908, FAM120AOS/rs944990, LMX1B/rs3829849, ADAM23/rs13387838, HOXB5/rs9299) were associated with BMI and seven (SEC16B/rs543874, OLFM4/rs12429545/rs9568856, FTO/rs9939609, MC4R/rs6567160, GNPDA2 rs13130484, LMX1B/rs3829849) were associated with obesity in Central Mexican children. One SNP was associated with obesity in Northern Mexicans and Yaquis (SEC16B/rs543874). We found higher BMI z-score at higher GRS (ß = 0.11, p = 0.2 × 10-16) and at lower AMA (ß = -0.05, p = 6.8 × 10-7). The GRS interacts with AMA to increase BMI (ß = 0.03, p = 6.08 × 10-3). High genetic BMI susceptibility increase the risk of higher BMI, including in Amerindian children.


Assuntos
Sobrepeso/genética , Obesidade Pediátrica/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Índice de Massa Corporal , Criança , Pré-Escolar , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Índios Norte-Americanos/genética , Masculino , México/epidemiologia , Sobrepeso/epidemiologia , Obesidade Pediátrica/epidemiologia
7.
Int J Legal Med ; 134(1): 199-202, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31707567

RESUMO

We analyzed 307 Mexican-Mestizo (admixed) males from Mexico City with the Powerplex® Y23 system. The complete list of Y-STR haplotypes was uploaded into the YHRD database (accession number YA004275). The discriminatory capacity (98.70 %) and gene diversity (D = 99.99 %) were calculated, improving the haplotype diversity regarding previous studies in Mexico based on 17 Y-STRs and 12 Y-STRs. Haplogroup distribution assignment was inferred by means of two different online-available algorithms. The Native American Q* haplogroup was the most frequent (66.2 %), followed by the European R1b lineage (19.5 %). In addition, eight Eurasian (3.9%) and two African (6.6%) haplogroups were observed in this population sample from Mexico City. Interestingly, AMOVA test showed a low but significant differentiation among Mexican-Mestizos (Fst = 1.52%; p = 0.0000), suggesting that four population clusters allow to explain their genetic structure according to geographic criteria: north, west, center, and south.


Assuntos
Cromossomos Humanos Y , Frequência do Gene , Haplótipos , Índios Norte-Americanos/genética , Repetições de Microssatélites , Polimorfismo de Nucleotídeo Único , Grupo com Ancestrais do Continente Africano/genética , Análise por Conglomerados , Bases de Dados Genéticas , Grupos Étnicos/genética , Grupo com Ancestrais do Continente Europeu/genética , Genética Populacional/métodos , Humanos , Masculino , México/etnologia
8.
Pharmacogenet Genomics ; 30(1): 1-4, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31651720

RESUMO

TPMT and NUDT15 polymorphisms are major determinants of tolerance to thiopurine drugs used in leukemias and nonmalignant immunologic disorders. We adopted an extreme discordant phenotype approach to explore the impact of Native American versus European ancestry on the distribution of TPMT and NUDT15 polymorphisms, and inferred metabolic phenotypes in the 1000 Genomes Ad Mixed American superpopulation. Significant differences were observed in the distribution of TPMT and NUDT15 haplotypes (star alleles) between individuals with predominant (>70%) European versus Native ancestry. The largest difference is related to NUDT15 rs116855232. Based on the combined TPMT/NUDT15 metabolic phenotypes, the Clinical Pharmacogenetics Implementation Consortium recommendations for thiopurine dose adjustment applies to 40.1% of individuals with major Native American ancestry, compared to 12.8% of individuals with predominantly European ancestry. These findings may be relevant to the adoption and interpretation of pharmacogenetic tests for thiopurine drugs across Latin America peoples with different European and Native-American ancestries.


Assuntos
Azatioprina/administração & dosagem , Grupo com Ancestrais do Continente Europeu/genética , Índios Norte-Americanos/genética , Metiltransferases/genética , Polimorfismo de Nucleotídeo Único , Pirofosfatases/genética , Antimetabólitos , Genótipo , Haplótipos , Humanos , América Latina/etnologia , Variantes Farmacogenômicos , Purinas
9.
Nicotine Tob Res ; 22(6): 910-918, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-31241144

RESUMO

INTRODUCTION: Alaska Native and American Indian (AN/AI) populations have higher tobacco use prevalence than other ethnic/racial groups. Pharmacogenetic testing to tailor tobacco cessation treatment may improve cessation rates. This study characterized polymorphic variations among AN/AI people in genes associated with metabolism of nicotine and drugs used for tobacco cessation. METHODS: Recruitment of AN/AI individuals represented six subgroups, five geographic subgroups throughout Alaska and a subgroup comprised of AIs from the lower 48 states living in Alaska. We sequenced the CYP2A6 and CYP2B6 genes to identify known and novel gain, reduced, and loss-of-function alleles, including structural variation (eg, gene deletions, duplications, and hybridizations). RESULTS: Variant allele frequencies differed substantially between AN/AI subgroups. The gene deletion CYP2A6*4 and reduced function CYP2A6*9 alleles were found at high frequency in Northern/Western subgroups and in Lower 48/Interior subgroups, respectively. The reduced function CYP2B6*6 allele was observed in all subgroups and a novel, predicted reduced function CYP2B6 variant was found at relatively high frequency in the Southeastern subgroup. CONCLUSIONS: Diverse CYP2A6 and CYP2B6 variation among the subgroups highlight the need for comprehensive pharmacogenetic testing to guide tobacco cessation therapy for AN/AI populations. IMPLICATIONS: Nicotine metabolism is largely determined by CYP2A6 genotype, and variation in CYP2A6 activity has altered the treatment success in other populations. These findings suggest pharmacogenetic-guided smoking cessation drug treatment could provide benefit to this unique population seeking tobacco cessation therapy.


Assuntos
Citocromo P-450 CYP2A6/genética , Citocromo P-450 CYP2B6/genética , Nicotina/metabolismo , Farmacogenética , Agentes de Cessação do Hábito de Fumar/farmacologia , Fumar/tratamento farmacológico , Fumar/genética , Adolescente , Adulto , Idoso , Alaska , /estatística & dados numéricos , Variação Genética , Genótipo , Humanos , Índios Norte-Americanos/genética , Índios Norte-Americanos/estatística & dados numéricos , Pessoa de Meia-Idade , Fumar/epidemiologia , Abandono do Hábito de Fumar/métodos , Adulto Jovem
10.
Clin Pharmacol Ther ; 107(1): 257-268, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31376146

RESUMO

We present the distribution of CYP2D6, CYP2C9, and CYP2C19 variants and predicted phenotypes in 33 native and admixed populations from Ibero-America (n > 6,000) in the context of genetic ancestry (n = 3,387). Continental ancestries are the major determinants of frequencies of the increased-activity allele CYP2C19*17 and CYP2C19 gUMs (negatively associated with Native American ancestry), decreased-activity alleles CYP2D6*41 and CYP2C9*2 (positively associated with European ancestry), and decreased-activity alleles CYP2D6*17 and CYP2D6*29 (positively associated with African ancestry). For the rare alleles, CYP2C9*2 and CYPC19*17, European admixture accounts for their presence in Native American populations, but rare alleles CYP2D6*5 (null-activity), CYP2D6-multiplication alleles (increased activity), and CYP2C9*3 (decreased-activity) were present in the pre-Columbian Americas. The study of a broad spectrum of Native American populations from different ethno-linguistic groups show how autochthonous diversity shaped the distribution of pharmaco-alleles and give insights on the prevalence of clinically relevant phenotypes associated with drugs, such as paroxetine, tamoxifen, warfarin, and clopidogrel.


Assuntos
Grupos de Populações Continentais/genética , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C9/genética , Citocromo P-450 CYP2D6/genética , Grupo com Ancestrais do Continente Africano/genética , Alelos , Grupo com Ancestrais do Continente Europeu/genética , Variação Genética , Genômica , Humanos , Índios Norte-Americanos/genética , América Latina , Fenótipo
11.
PLoS One ; 14(12): e0225030, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31790415

RESUMO

The Mexican population is characterized by high and particular admixture, and the picture of variants associated with disease remains unclear. Here we investigated the distribution of single nucleotide polymorphisms (SNPs) in the Mexican population. We focused on two non-synonymous and three synonymous SNPs in the beta-2 adrenergic receptor gene (ADRB2), which plays key roles in energy balance regulation. These SNPs were genotyped in 2,011 Mexican Amerindians (MAs) belonging to 62 ethnic groups and in 1,980 geographically matched Mexican Mestizos (MEZs). The frequency distribution of all five ADRB2 variants significantly differed between MAs, MEZs, and other continental populations (CPs) from the 1000 Genomes database. Allele frequencies of the three synonymous SNPs rs1042717A, rs1042718A, and rs1042719C were significantly higher in Mexican individuals, particularly among MAs, compared to in the other analyzed populations (P<0.05). The non-synonymous ADRB2 Glu27 allele (rs1042714G), which is associated with several common conditions, showed the lowest frequency in MAs (0.03) compared to other populations worldwide. Among MEZs, this allele showed a frequency of 0.15, intermediate between that in MAs and in Iberians (0.43). Moreover, Glu27 was the only SNP exhibiting a geographic gradient within the MEZ population (from 0.22 to 0.11), reflecting admixed mestizo ancestry across the country. Population differentiation analysis demonstrated that Glu27 had the highest FST value in MAs compared with Europeans (CEU) (0.71), and the lowest between MAs and Japanese (JPT) (0.01), even lower than that observed between MAs and MEZs (0.08). This analysis demonstrated the genetic diversity among Amerindian ethnicities, with the most extreme FST value (0.34) found between the Nahuatls from Morelos and the Seris. This is the first study of ADRB2 genetic variants among MA ethnicities. Our findings add to our understanding of the genetic contribution to variability in disease susceptibility in admixed populations.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Grupos Étnicos/genética , Grupo com Ancestrais do Continente Europeu/genética , Genética Populacional/métodos , Índios Norte-Americanos/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores Adrenérgicos beta 2/genética , Adulto , África/etnologia , Alelos , Europa (Continente)/etnologia , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Haplótipos/genética , Humanos , Masculino , México/etnologia
12.
J Health Care Poor Underserved ; 30(4S): 21-26, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31735714

RESUMO

"Changing the conversation" around genomic research with U.S. tribal communities may lead to new pathways to address persistent health disparities. Restoring trustworthiness between researchers and communities entails a willingness to listen to Indigenous voices, being flexible, and refining existing policies and frameworks to adapt to communities' needs.


Assuntos
/genética , Genômica/ética , Genômica/métodos , Disparidades nos Níveis de Saúde , Índios Norte-Americanos/genética , Participação da Comunidade/métodos , Competência Cultural , Meio Ambiente , Comitês de Ética em Pesquisa/organização & administração , Ética em Pesquisa , Humanos , Liderança , Estados Unidos
13.
PLoS One ; 14(10): e0223574, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31622379

RESUMO

BACKGROUND: Increased serum levels of C-reactive protein (CRP), an important component of the innate immune response, are associated with increased risk of cardiovascular disease (CVD). Multiple single nucleotide polymorphisms (SNP) have been identified which are associated with CRP levels, and Mendelian randomization studies have shown a positive association between SNPs increasing CRP expression and risk of colon cancer (but thus far not CVD). The effects of individual genetic variants often interact with the genetic background of a population and hence we sought to resolve the genetic determinants of serum CRP in a number of American Indian populations. METHODS: The Strong Heart Family Study (SHFS) has serum CRP measurements from 2428 tribal members, recruited as large families from three regions of the United States. Microsatellite markers and MetaboChip defined SNP genotypes were incorporated into variance components, decomposition-based linkage and association analyses. RESULTS: CRP levels exhibited significant heritability (h2 = 0.33 ± 0.05, p<1.3 X 10-20). A locus on chromosome (chr) 6, near marker D6S281 (approximately at 169.6 Mb, GRCh38/hg38) showed suggestive linkage (LOD = 1.9) to CRP levels. No individual SNPs were found associated with CRP levels after Bonferroni adjustment for multiple testing (threshold <7.77 x 10-7), however, we found nominal associations, many of which replicate previous findings at the CRP, HNF1A and 7 other loci. In addition, we report association of 46 SNPs located at 7 novel loci on chromosomes 2, 5, 6(2 loci), 9, 10 and 17, with an average of 15.3 Kb between SNPs and all with p-values less than 7.2 X 10-4. CONCLUSION: In agreement with evidence from other populations, these data show CRP serum levels are under considerable genetic influence; and include loci, such as near CRP and other genes, that replicate results from other ethnic groups. These findings also suggest possible novel loci on chr 6 and other chromosomes that warrant further investigation.


Assuntos
Biomarcadores , Proteína C-Reativa/genética , Variação Genética , Genética Populacional , Índios Norte-Americanos/genética , Alelos , Biomarcadores/sangue , Feminino , Ligação Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único
14.
Forensic Sci Int Genet ; 43: 102143, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31473588

RESUMO

Mitochondrial haplogroup information can be useful in forensic contexts that rely primarily on mitochondrial DNA (mtDNA) testing, which often involve limited or degraded DNA. Due to the phylogeographic patterning of mtDNA in human populations, mitochondrial haplogroups are indicative of maternal ancestry (as mtDNA is a maternally inherited marker). In certain circumstances, maternal ancestry inferred from mitochondrial haplogrouping could be beneficial to forensic investigations. For example, ancestry information could assist in the identification of unknown service members from past conflicts, such as the World War II Battle of Tarawa involving American and Japanese forces. In this context, it could be useful to distinguish Native American mtDNA from Asian mtDNA to bolster the anthropological and circumstantial evidence leading to an identification or foreign national determination. Although most of the founding Native American haplogroups contain diagnostic variants in the mitochondrial control region (CR), haplogroup B2 does not, and this makes it more difficult to distinguish B2 from the parental B4 and closely related B4b haplogroups found in Asia. In this paper, the amount of mtDNA information required to distinguish Native American haplotypes from Asian haplotypes within haplogroup B was examined. Fifty-six samples belonging to subtypes of B2 and B4 were sequenced for the entire mitogenome. Haplogroups were estimated from three ranges of mitochondrial DNA (HV1 and 2, CR, and full mitogenome). Half of the samples could not be precisely haplogrouped without full mitogenome data, although enough variants were often provided to make an accurate B2 versus B4 distinction. Native American B2 haplotypes were distinguishable using CR data alone in 82% of samples, though the remaining samples required full mitogenome data for haplogroup B2 designation. The use of full mitogenome data consistently enables accurate haplogroup determination, and opens the possibility for gaining information on maternal ancestry.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , DNA Mitocondrial/genética , Genoma Mitocondrial , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Índios Norte-Americanos/genética , Humanos , Filogenia , Reação em Cadeia da Polimerase , Análise de Sequência de DNA
15.
PLoS Genet ; 15(9): e1008225, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31545791

RESUMO

European and African descendants settled the continental US during the 17th-19th centuries, coming into contact with established Native American populations. The resulting admixture among these groups yielded a significant reservoir of Native American ancestry in the modern US population. We analyzed the patterns of Native American admixture seen for the three largest genetic ancestry groups in the US population: African descendants, Western European descendants, and Spanish descendants. The three groups show distinct Native American ancestry profiles, which are indicative of their historical patterns of migration and settlement across the country. Native American ancestry in the modern African descendant population does not coincide with local geography, instead forming a single group with origins in the southeastern US, consistent with the Great Migration of the early 20th century. Western European descendants show Native American ancestry that tracks their geographic origins across the US, indicative of ongoing contact during westward expansion, and Native American ancestry can resolve Spanish descendant individuals into distinct local groups formed by more recent migration from Mexico and Puerto Rico. We found an anomalous pattern of Native American ancestry from the US southwest, which most likely corresponds to the Nuevomexicano descendants of early Spanish settlers to the region. We addressed a number of controversies surrounding this population, including the extent of Sephardic Jewish ancestry. Nuevomexicanos are less admixed than nearby Mexican-American individuals, with more European and less Native American and African ancestry, and while they do show demonstrable Sephardic Jewish ancestry, the fraction is no greater than seen for other New World Spanish descendant populations.


Assuntos
Migração Humana/tendências , Índios Norte-Americanos/genética , Grupo com Ancestrais do Continente Africano/genética , Grupo com Ancestrais do Continente Europeu/genética , Genética Populacional/métodos , Genoma Humano/genética , Geografia , Haplótipos , Hispano-Americanos/genética , Humanos , Americanos Mexicanos/genética , Estados Unidos
16.
Genome Biol Evol ; 11(9): 2468-2479, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31384924

RESUMO

Inorganic arsenic (As) is a toxic xenobiotic and carcinogen associated with severe health conditions. The urban population from the Atacama Desert in northern Chile was exposed to extremely high As levels (up to 600 µg/l) in drinking water between 1958 and 1971, leading to increased incidence of urinary bladder cancer (BC), skin cancer, kidney cancer, and coronary thrombosis decades later. Besides, the Andean Native-American ancestors of the Atacama population were previously exposed for millennia to elevated As levels in water (∼120 µg/l) for at least 5,000 years, suggesting adaptation to this selective pressure. Here, we performed two genome-wide selection tests-PBSn1 and an ancestry-enrichment test-in an admixed population from Atacama, to identify adaptation signatures to As exposure acquired before and after admixture with Europeans, respectively. The top second variant selected by PBSn1 was associated with LCE4A-C1orf68, a gene that may be involved in the immune barrier of the epithelium during BC. We performed association tests between the top PBSn1 hits and BC occurrence in our population. The strongest association (P = 0.012) was achieved by the LCE4A-C1orf68 variant. The ancestry-enrichment test detected highly significant signals (P = 1.3 × 10-9) mapping MAK16, a gene with important roles in ribosome biogenesis during the G1 phase of the cell cycle. Our results contribute to a better understanding of the genetic factors involved in adaptation to the pathophysiological consequences of As exposure.


Assuntos
Arsênico/toxicidade , Polimorfismo de Nucleotídeo Único , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/genética , Poluentes Químicos da Água/toxicidade , Adaptação Fisiológica , Arsênico/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas Ricas em Prolina do Estrato Córneo/genética , Clima Desértico , Ambientes Extremos , Feminino , Humanos , Índios Norte-Americanos/genética , Masculino , Metiltransferases , Neoplasias/induzido quimicamente
17.
Sci Rep ; 9(1): 11027, 2019 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-31363122

RESUMO

Today, practical, functional and symbolic choices inform the selection of raw materials for worked objects. In cases where we can discern the origin of worked bone, tooth, ivory and antler objects in the past, we assume that similar choices are being made. However, morphological species identification of worked objects is often impossible due to the loss of identifying characteristics during manufacture. Here, we describe a novel non-destructive ZooMS (Zooarchaeology by Mass Spectrometry) method which was applied to bone points from Pre-Contact St. Lawrence Iroquoian village sites in southern Quebec, Canada. The traditional ZooMS technique requires destructive analysis of a sample, which can be problematic when dealing with artefacts. Here we instead extracted proteins from the plastic bags in which the points had been stored. ZooMS analysis revealed hitherto unexpected species, notably black bear (Ursus americanus) and human (Homo sapiens sapiens), used in point manufacture. These surprising results (confirmed through genomic sequencing) highlight the importance of advancing biomolecular research in artefact studies. Furthermore, they unexpectedly and exceptionally allow us to identify and explore the tangible, material traces of the symbolic relationship between bears and humans, central to past and present Iroquoian cosmology and mythology.


Assuntos
Antropologia Física/métodos , Arqueologia/métodos , Osso e Ossos/metabolismo , Genômica/métodos , Índios Norte-Americanos/genética , Animais , Canadá , Fósseis , Humanos , Ursidae/genética
18.
Science ; 365(6449)2019 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-31296740

RESUMO

North and South America were the last continents to be explored and settled by modern humans at the end of the Pleistocene. Genetic data, derived from contemporary populations and ancient individuals, show that the first Americans originated from Asia and after several population splits moved south of the continental ice sheets that covered Canada sometime between ~17.5 and ~14.6 thousand years (ka) ago. Archaeological evidence shows that geographically dispersed populations lived successfully, using biface, blade, and osseous technologies, in multiple places in North and South America between ~15.5 and ~14 ka ago. Regional archaeological complexes emerged by at least ~13 ka ago in North America and ~12.9 ka ago in South America. Current genetic and archaeological data do not support an earlier (pre-17.5 ka ago) occupation of the Americas.


Assuntos
Emigração e Imigração/história , Fluxo Gênico , Índios Norte-Americanos/genética , Índios Norte-Americanos/história , Antropologia , Arqueologia , Ásia/etnologia , História Antiga , Humanos , América do Norte , Sibéria/etnologia , América do Sul
20.
Am J Epidemiol ; 188(7): 1206-1212, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31081852

RESUMO

Research misconduct and consequential harms have been inflicted upon American Indian/Alaska Native communities for decades. To protect their people and culture and to retain oversight over research, many Native communities have established tribal health research and institutional review boards. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study showcases a successful, trusting research collaboration with tribal nations and academic investigators in Oklahoma. In 2006, the TODAY Study investigators proposed a modification of the study protocol to collect biological specimens from participants for genomic analyses and indefinite storage. Partnering American Indian tribal nations elected not to participate in the genomics collection and repository proposal. Reasons included 1) protection of cultural values, 2) concerns regarding community anonymity, 3) a potential threat to tribal services eligibility, 4) broad informed consent language, and 5) vague definitions of data access and usage. The nations believed the proposed genomics analyses presented a risk of harm to their people and nations without clear benefit. Since the 2006 proposal and the advancement of genomics research, many tribal communities in Oklahoma, appreciating the potential benefits of genomic research, are developing policies regarding oversight of/access to data and biological specimens to mitigate risks and provide members and communities with opportunities to participate in safe and meaningful genomic research.


Assuntos
Comportamento Cooperativo , Diabetes Mellitus Tipo 2/genética , Genômica , Índios Norte-Americanos/genética , Má Conduta Científica , Confiança , Humanos , Oklahoma
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