Neanderthal introgression in SCN9A impacts mechanical pain sensitivity.

The Nav1.7 voltage-gated sodium channel plays a key role in nociception. Three functional variants in the SCN9A gene (encoding M932L, V991L, and D1908G in Nav1.7), have recently been identified as stemming from Neanderthal introgression and to associate with pain symptomatology in UK BioBank data. In 1000 genomes data, these variants are absent in Europeans but common in Latin Americans. Analysing high-density genotype data from 7594 Latin Americans, we characterized Neanderthal introgression in SCN9A. We find that tracts of introgression occur on a Native American genomic background, have an average length of ~123 kb and overlap the M932L, V991L, and D1908G coding positions. Furthermore, we measured experimentally six pain thresholds in 1623 healthy Colombians. We found that Neanderthal ancestry in SCN9A is significantly associated with a lower mechanical pain threshold after sensitization with mustard oil and evidence of additivity of effects across Nav1.7 variants. Our findings support the reported association of Neanderthal Nav1.7 variants with clinical pain, define a specific sensory modality affected by archaic introgression in SCN9A and are consistent with independent effects of the Neanderthal variants on Nav1.7 function.

Missing persons patterns from Mexico: evidence of a forensic emergency crisis.

The relatives of missing persons in Mexico have denounced the slowness with which a court prosecution file is created by the justice administration system. Theoretically, the search is immediate, but many cases must wait 72 h to build an investigation folder as a legal criterion. This standard has been copied from the UK and Australian police reports without adapting to the Mexican context. The analysis of disappearance reports between 2006 and 2018 shows that this timing criterion in Mexico is not supported. The analyzed database (the National Center for Planning, Analysis, and Information to Combat Crime, CENAPI) showed that in the 72-h range, only 34.53% of the people had been found alive or dead; figure far from 50% to 80% of Europe or Australia. This fact shows that those searching officers or the judicial bureaucracy can act as a factor that limits the search for missing persons. Additionally, there is a random pattern in the geospatial distribution of disappearance, with non-homogeneous frequencies per year. Results highlight the participation of families, the adoption of an evidence-based model, and the generation of geospatial forensic intelligence analysis to generate evidence-based public policies. The social demand of families to the government for not considering them takes relevance in forensic practice in Mexico, and the disappearance data support this assertion.

Analysis of 14C concentration in teeth to estimate the year of birth in the Mexican population.

The 14C analysis of permanent teeth employing nuclear techniques has a direct application in Forensic Sciences since teeth are the hardest part of the human body and can survive natural decay or extreme conditions. After the first Accelerator Mass Spectrometry Laboratory AMS-LEMA at UNAM, our research group is interested in reproducing 14C analysis on teeth as other countries to estimate age in the Mexican population samples. One of the main goals of this exploratory study is to know the best methodology considering relevant biological factors based on differences in tissues (enamel and dentin) that allows us to know the year of birth through the 14C concentration comparing the yield between 14C analyses from carbonate in enamel and collagen in dentin. In this study, Accelerator Mass Spectrometry (AMS) has been performed in 22 contemporary teeth samples (each one donated from 1 different adult), participating 22 individuals by informed consent to enable a new tool and improve forensic practices in Mexico. Carbon is extracted, converted to graphite, and pressed into a cathode. The sample is taken to an AMS system, where carbon isotopes are separated, counted, and the 14C/12C and 13C/12C ratios determined. Our results for standards and teeth samples from Mexican people are in good agreement with the expected values; they are also useful to set up the best conditions for studies in dentin and enamel. However, this is a destructive technique for dental organs; it is not suitable for individuals born previous 1950. New challenges in sample preparation processes are to be solved to take advantage of the nuclear techniques developed in the last 50 years and make new contributions to society.

Physician Prehospital Care in Mexico City: Retrospective Analysis of Endotracheal Intubation in Patients with Severe Head Trauma.

INTRODUCTION: In Mexico, physicians have become part of public service prehospital care. Head injured patients are a sensitive group that can benefit from early advanced measures to protect the airway, with the objective to reduce hypoxia and maintain normocapnia. PROBLEM: The occurrence of endotracheal intubation to patients with severe head injuries by prehospital physicians working at Mexico City's Service of Emergency Medical Care (SAMU) is unknown. METHODS: A retrospective analysis of five-year data (2012-2016) from Mexico City's Medical Emergencies Regulation Center was performed. Only SAMU ambulance services were analyzed. Adult patients with a prehospital diagnosis of head injury based on mechanism of injury and physical examination with a Glasgow Coma Scale (GCS)

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.

Developmental pathways inferred from modularity, morphological integration and fluctuating asymmetry patterns in the human face.

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 performed on the same samples, indicating the action of different genomic regions contributing to the expression of the nose and mouth facial phenotypes. Our results also indicate that large samples including phenotypic and genomic metadata enable a better understanding of the developmental and genetic architecture of craniofacial phenotypes.

Correction: Socioeconomic Status Is Not Related with Facial Fluctuating Asymmetry: Evidence from Latin-American Populations.

[This corrects the article DOI: 10.1371/journal.pone.0169287.].

Socioeconomic Status Is Not Related with Facial Fluctuating Asymmetry: Evidence from Latin-American Populations.

The expression of facial asymmetries has been recurrently related with poverty and/or disadvantaged socioeconomic status. Departing from the developmental instability theory, previous approaches attempted to test the statistical relationship between the stress experienced by individuals grown in poor conditions and an increase in facial and corporal asymmetry. Here we aim to further evaluate such hypothesis on a large sample of admixed Latin Americans individuals by exploring if low socioeconomic status individuals tend to exhibit greater facial fluctuating asymmetry values. To do so, we implement Procrustes analysis of variance and Hierarchical Linear Modelling (HLM) to estimate potential associations between facial fluctuating asymmetry values and socioeconomic status. We report significant relationships between facial fluctuating asymmetry values and age, sex, and genetic ancestry, while socioeconomic status failed to exhibit any strong statistical relationship with facial asymmetry. These results are persistent after the effect of heterozygosity (a proxy for genetic ancestry) is controlled in the model. Our results indicate that, at least on the studied sample, there is no relationship between socioeconomic stress (as intended as low socioeconomic status) and facial asymmetries.

Mitochondrial DNA Analysis of Mazahua and Otomi Indigenous Populations from Estado de México Suggests a Distant Common Ancestry.

The indigenous Mazahua and Otomi have inhabited the same localities in Estado de México since pre-Columbian times. Their languages, Mazahua and Otomi, belong to the Oto-Manguean linguistic family, and although they share cultural traditions and a regional history that suggest close genetic relationships and common ancestry, the historical records concerning their origin are confusing. To understand the biological relationships between Mazahua and Otomi, we analyzed mitochondrial DNA (mtDNA) genetic variation. We identified the mtDNA haplogroups by restriction fragment length polymorphism typing and sequenced hypervariable region 1 of the mtDNA control region in 141 Mazahua and 100 Otomi. These results showed that Otomi exhibit a higher frequency of haplogroup A than B, whereas Mazahua exhibit the opposite pattern. In the Otomi EM population the most frequent subhaplogroups are, in order of frequency, A2, B2, and C1, whereas in the Mazahua 1 population they are B2, D1, and A2. The most frequent haplotypes (Ht) of haplogroups A and B are Ht2 (A) and Ht58 (B2g1) in Mazahua 1 and Ht8 (A2), Ht22 (A2ao1), and Ht53 (B2c2b) in Otomi EM. The genetic differences between the Mazahua 1 and Otomi EM suggest a distant shared ancestry and a moderate degree of maternal admixture that has not obscured the difference of their mtDNA patterns. These unexpected results suggest the Mazahua and Otomi probably descend from the same group but separated very early and admixed with other Mesoamerican populations before their arrival in Central Mexico. The historical evidence of conflicting relations between the Mazahua and Otomi and the almost nonexistence of marriage between them could be responsible for maintaining only a moderate degree of maternal admixture.

A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation.

We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values<5 × 10(-8)) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of ∼3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3. Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1. Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar funtion.

A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features.

We report a genome-wide association scan in over 6,000 Latin Americans for features of scalp hair (shape, colour, greying, balding) and facial hair (beard thickness, monobrow, eyebrow thickness). We found 18 signals of association reaching genome-wide significance (P values 5 × 10(-8) to 3 × 10(-119)), including 10 novel associations. These include novel loci for scalp hair shape and balding, and the first reported loci for hair greying, monobrow, eyebrow and beard thickness. A newly identified locus influencing hair shape includes a Q30R substitution in the Protease Serine S1 family member 53 (PRSS53). We demonstrate that this enzyme is highly expressed in the hair follicle, especially the inner root sheath, and that the Q30R substitution affects enzyme processing and secretion. The genome regions associated with hair features are enriched for signals of selection, consistent with proposals regarding the evolution of human hair.

Shifts in subsistence type and its impact on the human skull's morphological integration.

OBJECTIVE: Here we evaluate morphological integration patterns and magnitudes in different skull regions to detect if shifts in morphological integration are correlated to the appearance of more processed (softer) diets. METHODS: To do so, three transitional populations were analyzed, including samples from groups that inhabited the same geographical region and for which the evidence shows that major changes occurred in their subsistence mode. Ninety three-dimensional landmarks were digitized on 357 skulls and used as the raw data to develop geometric morphometric analyses. The landmark coordinates were divided into several different regions of biomechanical interest, following a three-level hierarchically nested scheme: the whole skull, further subdivided into neurocranium (divided into the vault and basicranium), the facial (divided into the lower and upper facial), and the masticatory apparatus (divided into alveolar, temporal, and temporo-mandibular joint). RESULTS: Our results indicate that the morphological integration and variability patterns significantly vary across skull regions but are maintained across the transitions. The alveolar border and the lower facial are the regions manifesting greater value of morphological integration and variability, while the upper facial, the temporo-mandibular joint, and the basicranium are highly integrated and poorly variable. CONCLUSIONS: The transition to softer diets increased morphological variation across cranial regions that are more exposed to masticatory strains effects.

A genome-wide association study identifies multiple loci for variation in human ear morphology.

Here we report a genome-wide association study for non-pathological pinna morphology in over 5,000 Latin Americans. We find genome-wide significant association at seven genomic regions affecting: lobe size and attachment, folding of antihelix, helix rolling, ear protrusion and antitragus size (linear regression P values 2 × 10(-8) to 3 × 10(-14)). Four traits are associated with a functional variant in the Ectodysplasin A receptor (EDAR) gene, a key regulator of embryonic skin appendage development. We confirm expression of Edar in the developing mouse ear and that Edar-deficient mice have an abnormally shaped pinna. Two traits are associated with SNPs in a region overlapping the T-Box Protein 15 (TBX15) gene, a major determinant of mouse skeletal development. Strongest association in this region is observed for SNP rs17023457 located in an evolutionarily conserved binding site for the transcription factor Cartilage paired-class homeoprotein 1 (CART1), and we confirm that rs17023457 alters in vitro binding of CART1.

Facial asymmetry and genetic ancestry in Latin American admixed populations.

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 estimators, especially when the analyses are aimed to compare levels of asymmetries on groups differing on socioeconomic levels, as a proxy to estimate developmental noise.

The relationship between facial shape asymmetry and attractiveness in Mexican students.

OBJECTIVES: It has been postulated that symmetric faces are considered more attractive than asymmetric ones because symmetry may signal high quality due to developmental stability. However, other studies showed that both symmetric and slightly asymmetric faces are considered attractive. Here we aim to explore this discrepancy, beginning with the analysis of the normal prevalence of facial symmetry in a population as a necessary first step prior to any attractiveness assessment. METHODS: We collected facial landmarks from two-dimensional digital images of a sample of Mexican individuals (280 females and 285 males aged 18-68 years) that were analyzed using geometric morphometric methods. Then, we chose a subsample of 100 photographs (50 females and 50 males aged 18-27 years) selected to represent a broad range of asymmetrical variation, in order to evaluate attractiveness using a sex-opposite test. Finally, we analyzed the linear correlation between attractiveness and asymmetry. RESULTS: We found that every evaluated subject presents some degree of facial asymmetry, and that both fluctuating asymmetry and directional asymmetry were significant (P < 0.0001) components of total facial asymmetry. Fluctuating asymmetry was slightly associated with age (r = 0.0858, P = 0.0414) and there were no differences between geographical regions (P = 0.413). Attractiveness was not correlated to levels of asymmetry in either sex (males: P = 0.0973; females P = 0.7415). CONCLUSIONS: Asymmetry was a prevalent feature in the present sample, and preferences for symmetric faces were not operating in the studied population.

Admixture in Latin America: geographic structure, phenotypic diversity and self-perception of ancestry based on 7,342 individuals.

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 self-perception 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.

FGFR1 signaling is associated with the magnitude of morphological integration in human head shape.

OBJECTIVES: The head can be used as a model to study complex phenotypes controlled simultaneously by morphological integration (MI) due to common factors, and modular patterns caused by local factors affecting the development and functional demands of specific structures. The fibroblast growth factor and receptor system (FGF/FGFR) participates in cell communication and pattern formation in osseous tissues, among others, and there is compelling evidence from mouse model studies suggesting a role of the FGF/FGFR pathway as a covariance-generating signaling process in head development. Here we use human data to test if specific genetic variants of another gene of this pathway, the FGFR1 gene, can be associated with differences in the integration of the head. METHODS: We explored whether and how three specific variants on FGFR1, previously associated with human cephalic index, influence the pattern and level of head integration of one Native American and one admixed group from Mexico. MI, measured as the intensity of covariation among head traits, was assessed using data from three-dimensional head landmark coordinates taken on 176 individuals. RESULTS: Individuals carrying the derived allele of the rs4647905:G>C polymorphism present significantly greater levels of head MI, especially in facial structures and on the shape space where the modular portion of the covariation is explicitly removed. CONCLUSIONS: Since FGFR genes present nonconservative and tissue-specific splicing sites, they may have some effect on protein structure and performance likely involved in developmental processes responsible for the magnitude and pattern of MI in the human head.

Lack of support for the association between facial shape and aggression: a reappraisal based on a worldwide population genetics perspective.

Antisocial and criminal behaviors are multifactorial traits whose interpretation relies on multiple disciplines. Since these interpretations may have social, moral and legal implications, a constant review of the evidence is necessary before any scientific claim is considered as truth. A recent study proposed that men with wider faces relative to facial height (fWHR) are more likely to develop unethical behaviour mediated by a psychological sense of power. This research was based on reports suggesting that sexual dimorphism and selection would be responsible for a correlation between fWHR and aggression. Here we show that 4,960 individuals from 94 modern human populations belonging to a vast array of genetic and cultural contexts do not display significant amounts of fWHR sexual dimorphism. Further analyses using populations with associated ethnographical records as well as samples of male prisoners of the Mexico City Federal Penitentiary condemned by crimes of variable level of inter-personal aggression (homicide, robbery, and minor faults) did not show significant evidence, suggesting that populations/individuals with higher levels of bellicosity, aggressive behaviour, or power-mediated behaviour display greater fWHR. Finally, a regression analysis of fWHR on individual's fitness showed no significant correlation between this facial trait and reproductive success. Overall, our results suggest that facial attributes are poor predictors of aggressive behaviour, or at least, that sexual selection was weak enough to leave a signal on patterns of between- and within-sex and population facial variation.

Comparison of methods to determine sex by evaluating the greater sciatic notch: Visual, angular and geometric morphometrics.

Sex estimation is the first step for biological profile reconstruction of an unknown skeleton (archaeological or contemporary) and consequently for positive identification of skeletal remains recovered from forensic settings. Several tools have been developed using different osseous structures. With the intention to provide an objective method comparison, we reported the analysis of three different methods (visual, metric and geometric morphometrics) for sex assessment of the greater sciatic notch. One hundred and thirty pelvic bones (45.4% females and 54.6% males) from the National Autonomous University of Mexico Skeletal Collection pertaining to the contemporary Mexican population were analyzed. We used the ROC-analysis to test between desired false positive thresholds (1-specificity) and expected true positive rates (sensitivity) in order to predict the best approach to sex assessment. The comparison of the area under the ROC-curves shows significant differences among visual and metric methods. At the same time, the analysis suggested that higher morphological variation among the sexes is independent of the methodological approach. The results indicate that the metric (angle), with a high percent of indeterminate cases (34.6%), and visual, with 26.2% of the cases allocated as intermediate cases, were poorly accurate; we cannot recommend these techniques for sexing an unknown specimen. On the other hand, the geometric morphometrics approach improves sex estimation in 82.3% of correctly classified individuals with more than 95% of posterior probability. In addition to the method comparison, the major sexual variation of the greater sciatic notch was determined to be located on its posterior border.