Population History and Gene Divergence in Native Mexicans Inferred from 76 Human Exomes.

Native American genetic variation remains underrepresented in most catalogs of human genome sequencing data. Previous genotyping efforts have revealed that Mexico's Indigenous population is highly differentiated and substructured, thus potentially harboring higher proportions of private genetic variants of functional and biomedical relevance. Here we have targeted the coding fraction of the genome and characterized its full site frequency spectrum by sequencing 76 exomes from five Indigenous populations across Mexico. Using diffusion approximations, we modeled the demographic history of Indigenous populations from Mexico with northern and southern ethnic groups splitting 7.2 KYA and subsequently diverging locally 6.5 and 5.7 KYA, respectively. Selection scans for positive selection revealed BCL2L13 and KBTBD8 genes as potential candidates for adaptive evolution in Rarámuris and Triquis, respectively. BCL2L13 is highly expressed in skeletal muscle and could be related to physical endurance, a well-known phenotype of the northern Mexico Rarámuri. The KBTBD8 gene has been associated with idiopathic short stature and we found it to be highly differentiated in Triqui, a southern Indigenous group from Oaxaca whose height is extremely low compared to other Native populations

Linguistic and maternal genetic diversity are not correlated in Native Mexicans

Mesoamerica, defined as the broad linguistic and cultural area from middle southern Mexico to Costa Rica, might have played a pivotal role during the colonization of the American continent. The Mesoamerican isthmus has constituted an important geographic barrier that has severely restricted gene flow between North and South America in pre-historical times. Although the Native American component has been already described in admixed Mexican populations, few studies have been carried out in native Mexican populations. In this study, we present mitochondrial DNA (mtDNA) sequence data for the first hypervariable region (HVR-I) in 477 unrelated individuals belonging to 11 different native populations from Mexico. Almost all of the Native Mexican mtDNAs could be classified into the four pan-Amerindian haplogroups (A2, B2, C1, and D1); only two of them could be allocated to the rare Native American lineage D4h3. Their haplogroup phylogenies are clearly star-like, as expected from relatively young populations that have experienced diverse episodes of genetic drift (e.g., extensive isolation, genetic drift, and founder effects) and posterior population expansions. In agreement with this observation, Native Mexican populations show a high degree of heterogeneity in their patterns of haplogroup frequencies. Haplogroup X2a was absent in our samples, supporting previous observations where this clade was only detected in the American northernmost areas. The search for identical sequences in the American continent shows that, although Native Mexican populations seem to show a closer relationship to North American populations, they cannot be related to a single geographical region within the continent. Finally, we did not find significant population structure in the maternal lineages when considering the four main and distinct linguistic groups represented in our Mexican samples (Oto-Manguean, Uto-Aztecan, Tarascan, and Mayan), suggesting that genetic divergence predates linguistic diversification in Mexico

Latin Americans show wide-spread Converso ancestry and imprint of local Native ancestry on physical appearance

Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly to the intermixing (admixture) of Native Americans, Europeans and Sub-Saharan Africans. Using novel haplotype-based methods, here we infer sub-continental ancestry in over 6,500 Latin Americans and evaluate the impact of regional ancestry variation on physical appearance. We find that Native American ancestry components in Latin Americans correspond geographically to the present-day genetic structure of Native groups, and that sources of non-Native ancestry, and admixture timings, match documented migratory flows. We also detect South/East Mediterranean ancestry across Latin America, probably stemming mostly from the clandestine colonial migration of Christian converts of non-European origin (Conversos). Furthermore, we find that ancestry related to highland (Central Andean) versus lowland (Mapuche) Natives is associated with variation in facial features, particularly nose morphology, and detect significant differences in allele frequencies between these groups at loci previously associated with nose morphology in this sample.Instituto Multidisciplinario de Biología Celula

Latin Americans show wide-spread Converso ancestry and imprint of local Native ancestry on physical appearance

Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly to the intermixing (admixture) of Native Americans, Europeans and Sub-Saharan Africans. Using novel haplotype-based methods, here we infer sub-continental ancestry in over 6,500 Latin Americans and evaluate the impact of regional ancestry variation on physical appearance. We find that Native American ancestry components in Latin Americans correspond geographically to the present-day genetic structure of Native groups, and that sources of non-Native ancestry, and admixture timings, match documented migratory flows. We also detect South/East Mediterranean ancestry across Latin America, probably stemming mostly from the clandestine colonial migration of Christian converts of non-European origin (Conversos). Furthermore, we find that ancestry related to highland (Central Andean) versus lowland (Mapuche) Natives is associated with variation in facial features, particularly nose morphology, and detect significant differences in allele frequencies between these groups at loci previously associated with nose morphology in this sample.Instituto Multidisciplinario de Biología Celula

Linguistic and maternal genetic diversity are not correlated in native mexicans

Mesoamerica, defined as the broad linguistic and cultural area from middle southern Mexico to Costa Rica, might have played a pivotal role during the colonization of the/nAmerican continent. It has been suggested that the Mesoamerican isthmus could have played an important role in severely restricting prehistorically gene flow between North and South/nAmerica. Although the Native American component has been already described in admixed/nMexican populations, few studies have been carried out in native Mexican populations. In this/nstudy we present mitochondrial DNA (mtDNA) sequence data for the first hypervariable region (HVR-I) in 477 unrelated individuals belonging to eleven different native populations from Mexico. Almost all the Native Mexican mtDNAs could be classified into the four pan-Amerindian haplogroups (A2, B2, C1 and D1); only three of them could be allocated to the rare Native American lineage D4h3. Their haplogroup phylogenies are clearly star-like, as expected from relatively young populations that have experienced diverse episodes of genetic drift (e.g. extensive isolation, genetic drift and founder effects) and posterior population expansions. In agreement with this observation is the fact that Native Mexican populations show a high degree of heterogeneity in their patterns of haplogroup frequencies. Haplogroup/nX2a was absent in our samples, supporting previous observations where this clade was only detected in the American northernmost areas. The search for identical sequences in the American continent shows that, although Native Mexican populations seem to show a closer relationship to North American populations, they cannot be related to a single geographical region within the continent. Finally, we did not find significant population structure on the maternal lineages when considering the four main and distinct linguistic groups represented in our Mexican samples (Oto-Manguean, Uto-Aztecan, Tarascan, and Mayan), suggesting that genetic divergence predates linguistic diversification in Mexico

Y-chromosome diversity in native mexicans reveals continental transition of genetic structure in the Americas

The genetic characterization of Native Mexicans is important to understand multiethnic based features influencing the medical genetics of present Mexican populations, as well as to the reconstruct the peopling of the Americas. We describe the Y-chromosome genetic diversity of 197 Native Mexicans from 11 populations and 1,044 individuals from 44 Native American populations after combining with publicly available data. We found extensive heterogeneity among Native Mexican populations and ample segregation of Q-M242* (46%) and Q-M3 (54%) haplogroups within Mexico. The northernmost sampled populations falling outside Mesoamerica (Pima and Tarahumara) showed a clear differentiation with respect to the other populations, which is in agreement with previous results from mtDNA lineages. However, our results point toward a complex genetic makeup of Native Mexicans whose maternal and paternal lineages reveal different narratives of their population history, with sex-biased continental contributions and different admixture proportions. At a continental scale, we found that Arctic populations and the northernmost groups from North America cluster together, but we did not find a clear differentiation within Mesoamerica and the rest of the continent, which coupled with the fact that the majority of individuals from Central and South American samples are restricted to the Q-M3 branch, supports the notion that most Native Americans from Mesoamerica southwards are descendants from a single wave of migration. This observation is compatible with the idea that present day Mexico might have constituted an area of transition in the diversification of paternal lineages during the colonization of the Americas

Population History and Gene Divergence in Native Mexicans Inferred from 76 Human Exomes.

Native American genetic variation remains underrepresented in most catalogs of human genome sequencing data. Previous genotyping efforts have revealed that Mexico's Indigenous population is highly differentiated and substructured, thus potentially harboring higher proportions of private genetic variants of functional and biomedical relevance. Here we have targeted the coding fraction of the genome and characterized its full site frequency spectrum by sequencing 76 exomes from five Indigenous populations across Mexico. Using diffusion approximations, we modeled the demographic history of Indigenous populations from Mexico with northern and southern ethnic groups splitting 7.2 KYA and subsequently diverging locally 6.5 and 5.7 KYA, respectively. Selection scans for positive selection revealed BCL2L13 and KBTBD8 genes as potential candidates for adaptive evolution in Rarámuris and Triquis, respectively. BCL2L13 is highly expressed in skeletal muscle and could be related to physical endurance, a well-known phenotype of the northern Mexico Rarámuri. The KBTBD8 gene has been associated with idiopathic short stature and we found it to be highly differentiated in Triqui, a southern Indigenous group from Oaxaca whose height is extremely low compared to other Native populations

Factors associated with degree of atopy in Latino children in a nationwide pediatric sample: the Genes-environments and Admixture in Latino Asthmatics (GALA II) study.

BackgroundAtopy varies by ethnicity, even within Latino groups. This variation might be due to environmental, sociocultural, or genetic factors.ObjectiveWe sought to examine risk factors for atopy within a nationwide study of US Latino children with and without asthma.MethodsAeroallergen skin test responses were analyzed in 1830 US Latino subjects. Key determinants of atopy included country/region of origin, generation in the United States, acculturation, genetic ancestry, and site to which subjects migrated. Serial multivariate zero-inflated negative binomial regressions stratified by asthma status examined the association of each key determinant variable with the number of positive skin test responses. In addition, the independent effect of each key variable was determined by including all key variables in the final models.ResultsIn baseline analyses African ancestry was associated with 3 times (95% CI, 1.62-5.57) as many positive skin test responses in asthmatic participants and 3.26 times (95% CI, 1.02-10.39) as many positive skin test responses in control participants. Generation and recruitment site were also associated with atopy in crude models. In final models adjusted for key variables, asthmatic patients of Puerto Rican (exp[β] [95% CI], 1.31 [1.02-1.69]) and mixed (exp[β] [95% CI], 1.27 [1.03-1.56]) ethnicity had a greater probability of positive skin test responses compared with Mexican asthmatic patients. Ancestry associations were abrogated by recruitment site but not region of origin.ConclusionsPuerto Rican ethnicity and mixed origin were associated with degree of atopy within US Latino children with asthma. African ancestry was not associated with degree of atopy after adjusting for recruitment site. Local environment variation, represented by site, was associated with degree of sensitization

Factors associated with degree of atopy in Latino children in a nationwide pediatric sample: The Genes-environments and Admixture in Latino Asthmatics (GALA II) study

BackgroundAtopy varies by ethnicity, even within Latino groups. This variation might be due to environmental, sociocultural, or genetic factors.ObjectiveWe sought to examine risk factors for atopy within a nationwide study of US Latino children with and without asthma.MethodsAeroallergen skin test responses were analyzed in 1830 US Latino subjects. Key determinants of atopy included country/region of origin, generation in the United States, acculturation, genetic ancestry, and site to which subjects migrated. Serial multivariate zero-inflated negative binomial regressions stratified by asthma status examined the association of each key determinant variable with the number of positive skin test responses. In addition, the independent effect of each key variable was determined by including all key variables in the final models.ResultsIn baseline analyses African ancestry was associated with 3 times (95% CI, 1.62-5.57) as many positive skin test responses in asthmatic participants and 3.26 times (95% CI, 1.02-10.39) as many positive skin test responses in control participants. Generation and recruitment site were also associated with atopy in crude models. In final models adjusted for key variables, asthmatic patients of Puerto Rican (exp[β] [95% CI], 1.31 [1.02-1.69]) and mixed (exp[β] [95% CI], 1.27 [1.03-1.56]) ethnicity had a greater probability of positive skin test responses compared with Mexican asthmatic patients. Ancestry associations were abrogated by recruitment site but not region of origin.ConclusionsPuerto Rican ethnicity and mixed origin were associated with degree of atopy within US Latino children with asthma. African ancestry was not associated with degree of atopy after adjusting for recruitment site. Local environment variation, represented by site, was associated with degree of sensitization