Mitochondrial adn (mt dna ) has been widely used as a genetic marker in studies of phylogeny and ... more Mitochondrial adn (mt dna ) has been widely used as a genetic marker in studies of phylogeny and human evolution. Its uniparental inheritability allows tracing the divergent maternal lineages among populations, as well as geographic dispersal routes. Dating these events becomes possible with the knowledge of their mutation rate. Variants contained within the genome can be grouped, identifying the occurrence of diagnostic mutations, in what is called haplogoups. In America there are five haplogroups that represent the diversity of our native populations (A, B, C, D and X). For purposes of this study, we analyzed sequences of the hypervariable region I of 50 individuals from two indigenous communities: Totonac and Nahua, both from the Sierra Norte de Puebla. The frequencies of mitochondrial haplogroups in these populations are consistent with those reported previously in wich haplogroup A2 is the most frequent (.74), followed by haplogroup B2 (.20); haplogroup D is present only in the...
A-receptor gene of ectodysplasin (WWTP) plays an important role in the development of certain org... more A-receptor gene of ectodysplasin (WWTP) plays an important role in the development of certain organs, especially those of ectodermal nature. A nonsynonymous variants of WWTP gene (V370A, T1540C, rs3827760) is proprietary to Asia and America, where it likely reached a high frequency by positive selection. 1540C allele has recently been linked to the shovel-shaped teeth in human groups of Japan, where it was estimated that approximately 19 % of the population describes the phenotypic diversity of this trait. We studied 91 unrelated individuals from Totonac in the Sierra Norte de Puebla, as well as 53 mestizos of Mexico City, with the purpose to report gene frequencies of this polymorphism. Our results show significant differences ( p < .01) of the 1540C allele frequency in the Totonac (.88) and mixed population (.48). These results are consistent with the higher 1540C allele frequencies observed in Northeast Asian populations and frequency in Native American populations. Moreover, ...
eye, hair and skin colour prediction respectively). When training prediction models on the CAN da... more eye, hair and skin colour prediction respectively). When training prediction models on the CAN data, we observe remarkably similar performances for HIrisPlex-S and the larger CAN SNP sets for the prediction of hair (categorical) and eye (both categorical and quantitative), while the CAN sets outperform HIrisPlex-S for quantitative, but not for categorical skin pigmentation prediction. The performance of HIrisPlex-S, when models are trained in a worldwide sample (although consisting of 80% Europeans, https://hirisplex.erasmusmc.nl), is lower relative to training in the CAN data (particularly for hair and skin colour). Altogether, our observations are consistent with common variation of eye and hair colour having a relatively simple genetic architecture, which is well captured by HIrisPlex-S, even in admixed Latin Americans (with partial European ancestry). By contrast, since skin pigmentation is a more polygenic trait, accuracy is more sensitive to prediction SNP set size, although here this effect was only apparent for a quantitative measure of skin pigmentation. Our results support the use of HIrisPlex-S in the prediction of categorical pigmentation traits for forensic purposes in Latin America, while illustrating the impact of training datasets on its accuracy.
We carried out a genome-wide association study in Latin Americans and identified novel face morph... more We carried out a genome-wide association study in Latin Americans and identified novel face morphology loci..
We report an evaluation of prediction accuracy for eye, hair and skin pigmentation based on genom... more We report an evaluation of prediction accuracy for eye, hair and skin pigmentation based on genomic and phenotypic data for over 6,500 admixed Latin Americans (the CANDELA dataset). We examined the impact on prediction accuracy of three main factors: (i) The methods of prediction, including classical statistical methods and machine learning approaches, (ii) The inclusion of non-genetic predictors, continental genetic ancestry and pigmentation SNPs in the prediction models, and (iii) Compared two sets of pigmentation SNPs: the commonly-used HIrisPlex-S set (developed in Europeans) and novel SNP sets we defined here based on genome-wide association results in the CANDELA sample. We find that Random Forest or regression are globally the best performing methods. Although continental genetic ancestry has substantial power for prediction of pigmentation in Latin Americans, the inclusion of pigmentation SNPs increases prediction accuracy considerably, particularly for skin color. For hair ...
We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and e... more We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and eyes. We found eighteen signals of association at twelve genomic regions. These include one novel locus for skin pigmentation (in 10q26) and three novel loci for eye pigmentation (in 1q32, 20q13 and 22q12). We demonstrate the presence of multiple independent signals of association in the 11q14 and 15q13 regions (comprising the GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles. Strongest association with skin pigmentation at 19p13 was observed for an Y182H missense variant (common only in East Asians and Native Americans) in MFSD12, a gene recently associated with skin pigmentation in Africans. We show that the frequency of the derived allele at Y182H is significantly correlated with lower solar radiation intensity in East Asia and infer that MFSD12 was under selection in East Asians, probably after their split from Europeans.
Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly... more 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.
The current genetic makeup of Latin America has been shaped by a history of extensive admixture b... more The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for selfperception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry.
Fluctuating and directional asymmetry are aspects of morphological variation widely used to infer... more Fluctuating and directional asymmetry are aspects of morphological variation widely used to infer environmental and genetic factors affecting facial phenotypes. However, the genetic basis and environmental determinants of both asymmetry types is far from being completely known. The analysis of facial asymmetries in admixed individuais can be of help to characterize the impact of a genome's heterozygosity on the deveiopmental basis of both fl.uctuating and directional asymmetries. Here we characterize the association between genetic ancestry and individual asymmetry on a sample of Latin-American admixed populations. To do Wiley Period.icals, Inc.
To characterize the genetic basis of facial features in Latin Americans, we performed a genome-wi... more To characterize the genetic basis of facial features in Latin Americans, we performed a genome-wide association study (GWAS) of more than 6000 individuals using 59 landmark-based measurements from two-dimensional profile photographs and ~9,000,000 genotyped or imputed single-nucleotide polymorphisms. We detected significant association of 32 traits with at least 1 (and up to 6) of 32 different genomic regions, more than doubling the number of robustly associated face morphology loci reported until now (from 11 to 23). These GWAS hits are strongly enriched in regulatory sequences active specifically during craniofacial development. The associated region in 1p12 includes a tract of archaic adaptive introgression, with a Denisovan haplotype common in Native Americans affecting particularly lip thickness. Among the nine previously unidentified face morphology loci we identified is the VPS13B gene region, and we show that variants in this region also affect midfacial morphology in mice.
We report an evaluation of prediction accuracy for eye, hair and skin pigmentation based on genom... more We report an evaluation of prediction accuracy for eye, hair and skin pigmentation based on genomic and phenotypic data for over 6,500 admixed Latin Americans (the CANDELA dataset). We examined the impact on prediction accuracy of three main factors: (i) The methods of prediction, including classical statistical methods and machine learning approaches, (ii) The inclusion of non-genetic predictors, continental genetic ancestry and pigmentation SNPs in the prediction models, and (iii) Compared two sets of pigmentation SNPs: the commonly-used HIrisPlex-S set (developed in Europeans) and novel SNP sets we defined here based on genome-wide association results in the CANDELA sample. We find that Random Forest or regression are globally the best performing methods. Although continental genetic ancestry has substantial power for prediction of pigmentation in Latin Americans, the inclusion of pigmentation SNPs increases prediction accuracy considerably, particularly for skin color. For hair and eye color, HIrisPlex-S has a similar performance to the CANDELA-specific prediction SNP sets. However, for skin pigmentation the performance of HIrisPlex-S is markedly lower than the SNP set defined here, including predictions in an independent dataset of Native American data. These results reflect the relatively high variation in hair and eye color among Europeans for whom HIrisPlex-S was developed, whereas their variation in skin pigmentation is comparatively lower. Furthermore, we show that the dataset used in the training of prediction models strongly impacts on the portability of these models across Europeans and Native Americans.
En este trabajo se evalúa la relación entre la asimetría fluctuante facial (AFF) y los tratami... more En este trabajo se evalúa la relación entre la asimetría fluctuante facial (AFF) y los tratamientos hormonales, cirugías maxilofaciales, ortodoncia, traumatismos y malformaciones. En el marco del proyecto CANDELA, se tomaron cinco fotografías faciales de 3162 voluntarios entre los 18 y 85 años. Por fotogrametría se colocaron 34 landmarks o puntos en 3D y mediante el método Procrustes ANOVA se obtuvieron valores individuales de asimetría fluctuante facial. Se realizó una prueba de ANOVA de una vía y la prueba de Welch y Levene para conocer las diferencias entre media y varianza de los valores de asimetría facial y las variables respuesta. También, se caracterizó la variación morfológica del componente asimétrico de la forma facial mediante técnicas multivariadas sobre los grupos que resultaran diferentes significativamente. Las mujeres que reportaron haber recibido algún tipo de tratamiento hormonal mostraron mayores valores de asimetría fluctuante facial respecto al grupo sin tratamiento. Esta asociación se mantuvo una vez removido el efecto de la heterocigosidad (como indicador de la ancestría) y sin interactuar con el resto de covariables incluidas en el análisis. Los cambios morfológicos asociados a este factor se concentran en el mentón, maxilar labio inferior, región perifrontal, región nasal y orejas. Algunos trabajos anteriores dieron cuenta de la posible relación entre la asimetría facial y los niveles de hormonas, pero no hay estudios que sustenten la relación causal o directa entre la asociación aquí planteada. El presente trabajo es una evidencia más de la asociación entre el consumo de hormonas y modificaciones de caracteres faciales en poblaciones urbanas mes- tizas latinoamericanas.
Fluctuating and directional asymmetry are aspects of morphological variation widely used to infer... more Fluctuating and directional asymmetry are aspects of morphological variation widely used to infer environmental and genetic factors affecting facial phenotypes. However, the genetic basis and environmental determinants of both asymmetry types is far from being completely known. The analysis of facial asymmetries in admixed individuals can be of help to characterize the impact of a genome's heterozygosity on the developmental basis of both fluctuating and directional asymmetries. Here we characterize the association between genetic ancestry and individual asymmetry on a sample of Latin-American admixed populations. To do so, three-dimensional (3D) facial shape attributes were explored on a sample of 4,104 volunteers aged between 18 and 85 years. Individual ancestry and heterozygosity was estimated using more than 730,000 genome-wide markers. Multivariate techniques applied to geometric morphometric data were used to evaluate the magnitude and significance of directional and fluctuating asymmetry (FA), as well as correlations and multiple regressions aimed to estimate the relationship between facial FA scores and heterozygosity and a set of covariates. Results indicate that directional and FA are both significant , the former being the strongest expression of asymmetry in this sample. In addition, our analyses suggest that there are some specific patterns of facial asymmetries characterizing the different ancestry groups. Finally, we find that more heterozygous individuals exhibit lower levels of asymmetry. Our results highlight the importance of including ancestry-admixture estima-tors, especially when the analyses are aimed to compare levels of asymmetries on groups differing on socioeconomic levels, as a proxy to estimate developmental noise. Am J Phys Anthropol 157:58–70, 2015.
We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and e... more We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and eyes. We found eighteen signals of association at twelve genomic regions. These include one novel locus for skin pigmentation (in 10q26) and three novel loci for eye pig-mentation (in 1q32, 20q13 and 22q12). We demonstrate the presence of multiple independent signals of association in the 11q14 and 15q13 regions (comprising the GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles. Strongest association with skin pigmentation at 19p13 was observed for anY182H missense variant (common only in East Asians and Native Americans) in MFSD12, a gene recently associated with skin pigmentation in Africans. We show that the frequency of the derived allele at Y182H is significantly correlated with lower solar radiation intensity inEast Asia and infer that MFSD12 was under selection in East Asians, probably after their split from Europeans.
Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly... more 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.
Facial asymmetries are usually measured and interpreted as proxies to developmental noise. Howeve... more Facial asymmetries are usually measured and interpreted as proxies to developmental noise. However, analyses focused on its developmental and genetic architecture are scarce. To advance on this topic, studies based on a comprehensive and simultaneous analysis of modularity, morphological integration and facial asymmetries including both phenotypic and genomic information are needed. Here we explore several modularity hypotheses on a sample of Latin American mestizos, in order to test if modularity and integration patterns differ across several genomic ancestry backgrounds. To do so, 4104 individuals were analyzed using 3D photogrammetry reconstructions and a set of 34 facial landmarks placed on each individual. We found a pattern of modularity and integration that is conserved across sub-samples differing in their genomic ancestry background. Specifically, a signal of modularity based on functional demands and organization of the face is regularly observed across the whole sample. Our results shed more light on previous evidence obtained from Genome Wide Association Studies
The major histocompatibility complex is directly involved in the immune
response and thus the gen... more The major histocompatibility complex is directly involved in the immune response and thus the genes coding for its proteins are useful markers for the study of genetic diversity, susceptibility to disease (autoimmunity and infections), transplant medicine, and pharmacogenetics, among others. The polymorphism of the system also allows researchers to use it as a proxy for population genetics analysis, such as genetic admixture and genetic structure. In order to determine the immunogenetic characteristics of a sample from the northern part of Mexico City and to use them to analyze the genetic differentiation from other admixed populations, including those from previous studies of Mexico City population, we analyzed molecular typing results of donors and patients from the Histocompatibility Laboratory of the Central Blood Bank of the Centro Médico Nacional La Raza selected according to their geographic origin. HLA-A, -B, -DRB1, and -DQB1 alleles were typed by PCR-SSP procedures. Allelic and haplotypic frequencies, as well as population genetics parameters, were obtained by maximum likelihood methods. The most frequent haplotypes found included HLA-A*02/-B*39/- DRB1*04/ DQB1*03:02P; HLA-A*02/-B*35/-DRB1*04/-DQB1*03:02P; HLA-A*68/-B*39/-DRB1*04/-DQB1*03:02P, and HLA-A*02/-B*35/-DRB1*08/-DQB1*04. Important to observe is that the second most frequent haplotype found in our sample (HLA-A*02/-B*35/-DRB1*04/- DQB1*03:02P) has not been previously reported in any mixed ancestry populations from Mexico but it is commonly encountered in Native American human groups, which can be a reflection on the impact of migration dynamics in the genetic conformation of the northern part of Mexico City, and the limitations of previous studies with regard to the genetic diversity of the analyzed groups. Differences found in haplotypic frequencies demonstrated that large urban conglomerates cannot be analyzed as one homogeneous entity, but rather should be understood as a set of structures in which social, political, and economical factors influence their genesis and dynamics.
Mitochondrial adn (mt dna ) has been widely used as a genetic marker in studies of phylogeny and ... more Mitochondrial adn (mt dna ) has been widely used as a genetic marker in studies of phylogeny and human evolution. Its uniparental inheritability allows tracing the divergent maternal lineages among populations, as well as geographic dispersal routes. Dating these events becomes possible with the knowledge of their mutation rate. Variants contained within the genome can be grouped, identifying the occurrence of diagnostic mutations, in what is called haplogoups. In America there are five haplogroups that represent the diversity of our native populations (A, B, C, D and X). For purposes of this study, we analyzed sequences of the hypervariable region I of 50 individuals from two indigenous communities: Totonac and Nahua, both from the Sierra Norte de Puebla. The frequencies of mitochondrial haplogroups in these populations are consistent with those reported previously in wich haplogroup A2 is the most frequent (.74), followed by haplogroup B2 (.20); haplogroup D is present only in the...
A-receptor gene of ectodysplasin (WWTP) plays an important role in the development of certain org... more A-receptor gene of ectodysplasin (WWTP) plays an important role in the development of certain organs, especially those of ectodermal nature. A nonsynonymous variants of WWTP gene (V370A, T1540C, rs3827760) is proprietary to Asia and America, where it likely reached a high frequency by positive selection. 1540C allele has recently been linked to the shovel-shaped teeth in human groups of Japan, where it was estimated that approximately 19 % of the population describes the phenotypic diversity of this trait. We studied 91 unrelated individuals from Totonac in the Sierra Norte de Puebla, as well as 53 mestizos of Mexico City, with the purpose to report gene frequencies of this polymorphism. Our results show significant differences ( p < .01) of the 1540C allele frequency in the Totonac (.88) and mixed population (.48). These results are consistent with the higher 1540C allele frequencies observed in Northeast Asian populations and frequency in Native American populations. Moreover, ...
eye, hair and skin colour prediction respectively). When training prediction models on the CAN da... more eye, hair and skin colour prediction respectively). When training prediction models on the CAN data, we observe remarkably similar performances for HIrisPlex-S and the larger CAN SNP sets for the prediction of hair (categorical) and eye (both categorical and quantitative), while the CAN sets outperform HIrisPlex-S for quantitative, but not for categorical skin pigmentation prediction. The performance of HIrisPlex-S, when models are trained in a worldwide sample (although consisting of 80% Europeans, https://hirisplex.erasmusmc.nl), is lower relative to training in the CAN data (particularly for hair and skin colour). Altogether, our observations are consistent with common variation of eye and hair colour having a relatively simple genetic architecture, which is well captured by HIrisPlex-S, even in admixed Latin Americans (with partial European ancestry). By contrast, since skin pigmentation is a more polygenic trait, accuracy is more sensitive to prediction SNP set size, although here this effect was only apparent for a quantitative measure of skin pigmentation. Our results support the use of HIrisPlex-S in the prediction of categorical pigmentation traits for forensic purposes in Latin America, while illustrating the impact of training datasets on its accuracy.
We carried out a genome-wide association study in Latin Americans and identified novel face morph... more We carried out a genome-wide association study in Latin Americans and identified novel face morphology loci..
We report an evaluation of prediction accuracy for eye, hair and skin pigmentation based on genom... more We report an evaluation of prediction accuracy for eye, hair and skin pigmentation based on genomic and phenotypic data for over 6,500 admixed Latin Americans (the CANDELA dataset). We examined the impact on prediction accuracy of three main factors: (i) The methods of prediction, including classical statistical methods and machine learning approaches, (ii) The inclusion of non-genetic predictors, continental genetic ancestry and pigmentation SNPs in the prediction models, and (iii) Compared two sets of pigmentation SNPs: the commonly-used HIrisPlex-S set (developed in Europeans) and novel SNP sets we defined here based on genome-wide association results in the CANDELA sample. We find that Random Forest or regression are globally the best performing methods. Although continental genetic ancestry has substantial power for prediction of pigmentation in Latin Americans, the inclusion of pigmentation SNPs increases prediction accuracy considerably, particularly for skin color. For hair ...
We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and e... more We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and eyes. We found eighteen signals of association at twelve genomic regions. These include one novel locus for skin pigmentation (in 10q26) and three novel loci for eye pigmentation (in 1q32, 20q13 and 22q12). We demonstrate the presence of multiple independent signals of association in the 11q14 and 15q13 regions (comprising the GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles. Strongest association with skin pigmentation at 19p13 was observed for an Y182H missense variant (common only in East Asians and Native Americans) in MFSD12, a gene recently associated with skin pigmentation in Africans. We show that the frequency of the derived allele at Y182H is significantly correlated with lower solar radiation intensity in East Asia and infer that MFSD12 was under selection in East Asians, probably after their split from Europeans.
Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly... more 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.
The current genetic makeup of Latin America has been shaped by a history of extensive admixture b... more The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for selfperception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry.
Fluctuating and directional asymmetry are aspects of morphological variation widely used to infer... more Fluctuating and directional asymmetry are aspects of morphological variation widely used to infer environmental and genetic factors affecting facial phenotypes. However, the genetic basis and environmental determinants of both asymmetry types is far from being completely known. The analysis of facial asymmetries in admixed individuais can be of help to characterize the impact of a genome's heterozygosity on the deveiopmental basis of both fl.uctuating and directional asymmetries. Here we characterize the association between genetic ancestry and individual asymmetry on a sample of Latin-American admixed populations. To do Wiley Period.icals, Inc.
To characterize the genetic basis of facial features in Latin Americans, we performed a genome-wi... more To characterize the genetic basis of facial features in Latin Americans, we performed a genome-wide association study (GWAS) of more than 6000 individuals using 59 landmark-based measurements from two-dimensional profile photographs and ~9,000,000 genotyped or imputed single-nucleotide polymorphisms. We detected significant association of 32 traits with at least 1 (and up to 6) of 32 different genomic regions, more than doubling the number of robustly associated face morphology loci reported until now (from 11 to 23). These GWAS hits are strongly enriched in regulatory sequences active specifically during craniofacial development. The associated region in 1p12 includes a tract of archaic adaptive introgression, with a Denisovan haplotype common in Native Americans affecting particularly lip thickness. Among the nine previously unidentified face morphology loci we identified is the VPS13B gene region, and we show that variants in this region also affect midfacial morphology in mice.
We report an evaluation of prediction accuracy for eye, hair and skin pigmentation based on genom... more We report an evaluation of prediction accuracy for eye, hair and skin pigmentation based on genomic and phenotypic data for over 6,500 admixed Latin Americans (the CANDELA dataset). We examined the impact on prediction accuracy of three main factors: (i) The methods of prediction, including classical statistical methods and machine learning approaches, (ii) The inclusion of non-genetic predictors, continental genetic ancestry and pigmentation SNPs in the prediction models, and (iii) Compared two sets of pigmentation SNPs: the commonly-used HIrisPlex-S set (developed in Europeans) and novel SNP sets we defined here based on genome-wide association results in the CANDELA sample. We find that Random Forest or regression are globally the best performing methods. Although continental genetic ancestry has substantial power for prediction of pigmentation in Latin Americans, the inclusion of pigmentation SNPs increases prediction accuracy considerably, particularly for skin color. For hair and eye color, HIrisPlex-S has a similar performance to the CANDELA-specific prediction SNP sets. However, for skin pigmentation the performance of HIrisPlex-S is markedly lower than the SNP set defined here, including predictions in an independent dataset of Native American data. These results reflect the relatively high variation in hair and eye color among Europeans for whom HIrisPlex-S was developed, whereas their variation in skin pigmentation is comparatively lower. Furthermore, we show that the dataset used in the training of prediction models strongly impacts on the portability of these models across Europeans and Native Americans.
En este trabajo se evalúa la relación entre la asimetría fluctuante facial (AFF) y los tratami... more En este trabajo se evalúa la relación entre la asimetría fluctuante facial (AFF) y los tratamientos hormonales, cirugías maxilofaciales, ortodoncia, traumatismos y malformaciones. En el marco del proyecto CANDELA, se tomaron cinco fotografías faciales de 3162 voluntarios entre los 18 y 85 años. Por fotogrametría se colocaron 34 landmarks o puntos en 3D y mediante el método Procrustes ANOVA se obtuvieron valores individuales de asimetría fluctuante facial. Se realizó una prueba de ANOVA de una vía y la prueba de Welch y Levene para conocer las diferencias entre media y varianza de los valores de asimetría facial y las variables respuesta. También, se caracterizó la variación morfológica del componente asimétrico de la forma facial mediante técnicas multivariadas sobre los grupos que resultaran diferentes significativamente. Las mujeres que reportaron haber recibido algún tipo de tratamiento hormonal mostraron mayores valores de asimetría fluctuante facial respecto al grupo sin tratamiento. Esta asociación se mantuvo una vez removido el efecto de la heterocigosidad (como indicador de la ancestría) y sin interactuar con el resto de covariables incluidas en el análisis. Los cambios morfológicos asociados a este factor se concentran en el mentón, maxilar labio inferior, región perifrontal, región nasal y orejas. Algunos trabajos anteriores dieron cuenta de la posible relación entre la asimetría facial y los niveles de hormonas, pero no hay estudios que sustenten la relación causal o directa entre la asociación aquí planteada. El presente trabajo es una evidencia más de la asociación entre el consumo de hormonas y modificaciones de caracteres faciales en poblaciones urbanas mes- tizas latinoamericanas.
Fluctuating and directional asymmetry are aspects of morphological variation widely used to infer... more Fluctuating and directional asymmetry are aspects of morphological variation widely used to infer environmental and genetic factors affecting facial phenotypes. However, the genetic basis and environmental determinants of both asymmetry types is far from being completely known. The analysis of facial asymmetries in admixed individuals can be of help to characterize the impact of a genome's heterozygosity on the developmental basis of both fluctuating and directional asymmetries. Here we characterize the association between genetic ancestry and individual asymmetry on a sample of Latin-American admixed populations. To do so, three-dimensional (3D) facial shape attributes were explored on a sample of 4,104 volunteers aged between 18 and 85 years. Individual ancestry and heterozygosity was estimated using more than 730,000 genome-wide markers. Multivariate techniques applied to geometric morphometric data were used to evaluate the magnitude and significance of directional and fluctuating asymmetry (FA), as well as correlations and multiple regressions aimed to estimate the relationship between facial FA scores and heterozygosity and a set of covariates. Results indicate that directional and FA are both significant , the former being the strongest expression of asymmetry in this sample. In addition, our analyses suggest that there are some specific patterns of facial asymmetries characterizing the different ancestry groups. Finally, we find that more heterozygous individuals exhibit lower levels of asymmetry. Our results highlight the importance of including ancestry-admixture estima-tors, especially when the analyses are aimed to compare levels of asymmetries on groups differing on socioeconomic levels, as a proxy to estimate developmental noise. Am J Phys Anthropol 157:58–70, 2015.
We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and e... more We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and eyes. We found eighteen signals of association at twelve genomic regions. These include one novel locus for skin pigmentation (in 10q26) and three novel loci for eye pig-mentation (in 1q32, 20q13 and 22q12). We demonstrate the presence of multiple independent signals of association in the 11q14 and 15q13 regions (comprising the GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles. Strongest association with skin pigmentation at 19p13 was observed for anY182H missense variant (common only in East Asians and Native Americans) in MFSD12, a gene recently associated with skin pigmentation in Africans. We show that the frequency of the derived allele at Y182H is significantly correlated with lower solar radiation intensity inEast Asia and infer that MFSD12 was under selection in East Asians, probably after their split from Europeans.
Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly... more 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.
Facial asymmetries are usually measured and interpreted as proxies to developmental noise. Howeve... more Facial asymmetries are usually measured and interpreted as proxies to developmental noise. However, analyses focused on its developmental and genetic architecture are scarce. To advance on this topic, studies based on a comprehensive and simultaneous analysis of modularity, morphological integration and facial asymmetries including both phenotypic and genomic information are needed. Here we explore several modularity hypotheses on a sample of Latin American mestizos, in order to test if modularity and integration patterns differ across several genomic ancestry backgrounds. To do so, 4104 individuals were analyzed using 3D photogrammetry reconstructions and a set of 34 facial landmarks placed on each individual. We found a pattern of modularity and integration that is conserved across sub-samples differing in their genomic ancestry background. Specifically, a signal of modularity based on functional demands and organization of the face is regularly observed across the whole sample. Our results shed more light on previous evidence obtained from Genome Wide Association Studies
The major histocompatibility complex is directly involved in the immune
response and thus the gen... more The major histocompatibility complex is directly involved in the immune response and thus the genes coding for its proteins are useful markers for the study of genetic diversity, susceptibility to disease (autoimmunity and infections), transplant medicine, and pharmacogenetics, among others. The polymorphism of the system also allows researchers to use it as a proxy for population genetics analysis, such as genetic admixture and genetic structure. In order to determine the immunogenetic characteristics of a sample from the northern part of Mexico City and to use them to analyze the genetic differentiation from other admixed populations, including those from previous studies of Mexico City population, we analyzed molecular typing results of donors and patients from the Histocompatibility Laboratory of the Central Blood Bank of the Centro Médico Nacional La Raza selected according to their geographic origin. HLA-A, -B, -DRB1, and -DQB1 alleles were typed by PCR-SSP procedures. Allelic and haplotypic frequencies, as well as population genetics parameters, were obtained by maximum likelihood methods. The most frequent haplotypes found included HLA-A*02/-B*39/- DRB1*04/ DQB1*03:02P; HLA-A*02/-B*35/-DRB1*04/-DQB1*03:02P; HLA-A*68/-B*39/-DRB1*04/-DQB1*03:02P, and HLA-A*02/-B*35/-DRB1*08/-DQB1*04. Important to observe is that the second most frequent haplotype found in our sample (HLA-A*02/-B*35/-DRB1*04/- DQB1*03:02P) has not been previously reported in any mixed ancestry populations from Mexico but it is commonly encountered in Native American human groups, which can be a reflection on the impact of migration dynamics in the genetic conformation of the northern part of Mexico City, and the limitations of previous studies with regard to the genetic diversity of the analyzed groups. Differences found in haplotypic frequencies demonstrated that large urban conglomerates cannot be analyzed as one homogeneous entity, but rather should be understood as a set of structures in which social, political, and economical factors influence their genesis and dynamics.
A mi madre Marcela, mi gran maestra A mi padre Oscar, quien siempre me ha apoyado A mis hermanos ... more A mi madre Marcela, mi gran maestra A mi padre Oscar, quien siempre me ha apoyado A mis hermanos Iván, Lener y Sofía mis compañeros de vida A mis sobrinos Renata, Gael e Ian 3 Agradecimientos El presente trabajo de investigación fue posible gracias a la iniciativa CANDELA, la cual recibió presupuesto de Leverhulme Trust Al esfuerzo conjunto de las instituciones e investigadores que impulsaron la conformación del Consorcio CANDELA. Especialmente a la guía y colaboración de colegas con quienes he ido construyendo este propósito de vida, al Dr. Samuel Canizales Quinteros, al Dr. Jorge Gómez Valdés y al Lic. Víctor Acuña Alonzo.
Por el Norte de Guerrero. Nuevas miradas desde la antropología y la historia, 2016
El actual estado de Guerrero es y ha sido un territorio en el cual se han asentado y desarrollado... more El actual estado de Guerrero es y ha sido un territorio en el cual se han asentado y desarrollado diversos grupos humanos, los cuales representan una labor compleja en cuanto al estudio de los diferentes factores sociales, culturales y biológicos acaecidos durante sus diversos momentos históricos. Esto se debe a que es una región que ha sido sometida a distintos cambios políticos, ideológicos y demográficos. En el presente trabajo se muestran algunos antecedentes sobre los distintos procesos históricos ocurridos en el actual estado de Guerrero, haciendo énfasis en la región norte. Después se presenta una revisión bibliográfica sobre los estudios más relevantes llevados a cabo en torno a la diversidad biológica de las poblaciones guerrerenses. Finalmente se resumen los objetivos del proyecto de investigación iniciado en 2010 sobre la genética antropológica de las poblaciones del norte de Guerrero y se exponen los resultados preliminares de la primera fase de estudio.
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Papers by Paola Everardo
GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles. Strongest association with skin pigmentation at 19p13 was observed for anY182H missense variant (common only in East Asians and Native Americans) in MFSD12, a gene recently associated with skin pigmentation in Africans. We show that the frequency of the derived allele at Y182H is significantly correlated with lower solar radiation intensity inEast Asia and infer that MFSD12 was under selection in East Asians, probably after their split from Europeans.
response and thus the genes coding for its proteins are useful markers for the study of genetic diversity, susceptibility to disease (autoimmunity and infections), transplant medicine, and pharmacogenetics, among others. The polymorphism of the system also allows researchers to use it as a proxy for population genetics analysis, such as genetic admixture and genetic structure. In order to determine the immunogenetic characteristics of a sample from the northern part of Mexico City and to use them to analyze the genetic differentiation from other admixed populations, including those from previous studies of Mexico City population, we analyzed molecular typing results of donors and patients from the Histocompatibility Laboratory of the Central Blood Bank of the Centro Médico Nacional La Raza selected according to their geographic origin. HLA-A, -B, -DRB1, and -DQB1 alleles were typed by PCR-SSP procedures.
Allelic and haplotypic frequencies, as well as population genetics parameters, were obtained by maximum likelihood methods. The most frequent haplotypes found included HLA-A*02/-B*39/- DRB1*04/ DQB1*03:02P; HLA-A*02/-B*35/-DRB1*04/-DQB1*03:02P; HLA-A*68/-B*39/-DRB1*04/-DQB1*03:02P, and HLA-A*02/-B*35/-DRB1*08/-DQB1*04. Important to observe is that the second most frequent haplotype found in our sample (HLA-A*02/-B*35/-DRB1*04/- DQB1*03:02P) has not been previously reported in any mixed ancestry populations from Mexico but it is commonly encountered in Native American human groups, which can be a
reflection on the impact of migration dynamics in the genetic conformation of the northern part of Mexico City, and the limitations of previous studies with regard to the genetic diversity of the analyzed groups. Differences found in haplotypic frequencies demonstrated that large urban conglomerates cannot be analyzed as one homogeneous entity, but rather should be understood as a set of structures in which social, political, and economical factors influence their genesis and dynamics.
GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles. Strongest association with skin pigmentation at 19p13 was observed for anY182H missense variant (common only in East Asians and Native Americans) in MFSD12, a gene recently associated with skin pigmentation in Africans. We show that the frequency of the derived allele at Y182H is significantly correlated with lower solar radiation intensity inEast Asia and infer that MFSD12 was under selection in East Asians, probably after their split from Europeans.
response and thus the genes coding for its proteins are useful markers for the study of genetic diversity, susceptibility to disease (autoimmunity and infections), transplant medicine, and pharmacogenetics, among others. The polymorphism of the system also allows researchers to use it as a proxy for population genetics analysis, such as genetic admixture and genetic structure. In order to determine the immunogenetic characteristics of a sample from the northern part of Mexico City and to use them to analyze the genetic differentiation from other admixed populations, including those from previous studies of Mexico City population, we analyzed molecular typing results of donors and patients from the Histocompatibility Laboratory of the Central Blood Bank of the Centro Médico Nacional La Raza selected according to their geographic origin. HLA-A, -B, -DRB1, and -DQB1 alleles were typed by PCR-SSP procedures.
Allelic and haplotypic frequencies, as well as population genetics parameters, were obtained by maximum likelihood methods. The most frequent haplotypes found included HLA-A*02/-B*39/- DRB1*04/ DQB1*03:02P; HLA-A*02/-B*35/-DRB1*04/-DQB1*03:02P; HLA-A*68/-B*39/-DRB1*04/-DQB1*03:02P, and HLA-A*02/-B*35/-DRB1*08/-DQB1*04. Important to observe is that the second most frequent haplotype found in our sample (HLA-A*02/-B*35/-DRB1*04/- DQB1*03:02P) has not been previously reported in any mixed ancestry populations from Mexico but it is commonly encountered in Native American human groups, which can be a
reflection on the impact of migration dynamics in the genetic conformation of the northern part of Mexico City, and the limitations of previous studies with regard to the genetic diversity of the analyzed groups. Differences found in haplotypic frequencies demonstrated that large urban conglomerates cannot be analyzed as one homogeneous entity, but rather should be understood as a set of structures in which social, political, and economical factors influence their genesis and dynamics.