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OBJECTIVE: To evaluate the genetic diversity, admixture, genetic relationships, and sex-biased demographic processes in Mexican Mestizo (admixed) populations based on 10 X-chromosome STRs (X-STRs). METHODS: We analyzed the X-STRs Decaplex system in 104 Mexican Native Americans to obtain the ancestral reference needed to complete the demographic analyses above mentioned. We included reported Iberian and Latin American (admixed) populations from Central and South America, as well as datasets from Mexican Mestizos based on Y-linked STRs (Y-STRs), autosomal STRs (A-STRs), and mtDNA. RESULTS: Higher X-linked Native American ancestry was observed among Latin American populations regarding that reported from A-STRs and Y-STRs. The interpopulation differentiation based on ancestry among Mexican Mestizos diminished according to the inheritance pattern: Y-STRs (highest), A-STRs, X-STRs, and mtDNA (lowest). This finding is related to the peculiar admixture process that occurred during and after the Spanish Conquest of Mexico (and most of Latin America), involving a large number of Spanish men (Y-chromosomes) with a lesser proportion of X-chromosomes than autosomes; besides to the limited number of Spanish women (XX) arrived in the Americas in subsequent and shorter periods. Population expansion was detected in Mexican Mestizos from all the country, except those from the southeast region characterized by elevated indigenous ancestry, marginalization, and poorness. CONCLUSIONS: Population growth was detected in most Mexican Mestizos, besides more homogeneous and larger Native American ancestry based on X-linked inheritance than that based on autosomal STRs and Y-STRs.
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Trachoma, caused by Chlamydia trachomatis, is the most common infectious blindness in the world and is present in indigenous Mayan from Chiapas (Mexico). Inflammatory genes are activated when suffering from trachoma, thus some polymorphisms could increase the susceptibility to develop irreversible blindness. This study aimed to evaluate the genetic risk of developing late-stage trachoma in Mayan ethnic groups. In a case-control study (n = 51 vs n = 102, respectively), the following single-nucleotide polymorphisms (SNPs) in genes related to inflammation were analysed: HSD11B1 (rs11807619), HSD11B1 (rs932335), ABCG2 (rs2231142), SLCO1B1 (rs4149056), IL-10 (rs1800890), TNF (rs1800629), MMP2 (rs243865) and ACE. Three SNPs were associated with late-stage trachoma risk: (i) the T allele of rs11807619, (ii) the C allele of rs932335, which are linked to the HSD11B1 gene (OR = 22.5-27.3), particularly in men when adjusts for gender (OR = 16-16.7); and (iii) D allele of rs4340 in the ACE gene (OR = 5.2-5.3). In fact, significant linkage disequilibrium demonstrated association between ACE gene and HSD11B1 SNPs (r = 0.17-0.179; P = 0.0048-0.0073). Two SNPs HSD11B1 gene (P = 0.013 vs 0.0039) and HSD11B1-ACE haplotypes showed association with late-stage trachoma in Mayan ethnic groups.
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11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1 , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Tracoma , Humanos , Tracoma/genética , Masculino , Femenino , Estudios de Casos y Controles , Adulto , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/genética , Persona de Mediana Edad , Alelos , Estudios de Asociación Genética , Haplotipos , Chlamydia trachomatis/genética , Frecuencia de los Genes , Genotipo , Peptidil-Dipeptidasa ARESUMEN
Until a few years ago, it was believed that the gradual mosaic loss of the Y chromosome (mLOY) was a normal age-related process. However, it is now known that mLOY is associated with a wide variety of pathologies in men, such as cardiovascular diseases, neurodegenerative disorders, and many types of cancer. Nevertheless, the mechanisms that generate mLOY in men have not been studied so far. This task is of great importance because it will allow focusing on possible methods of prophylaxis or therapy for diseases associated with mLOY. On the other hand, it would allow better understanding of mLOY as a possible marker for inferring the age of male samples in cases of human identification. Due to the above, in this work, a comprehensive review of the literature was conducted, presenting the most relevant information on the possible molecular mechanisms by which mLOY is generated, as well as its implications for men's health and its possible use as a marker to infer age.
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Cromosomas Humanos Y , Salud del Hombre , Humanos , Cromosomas Humanos Y/genética , Masculino , Envejecimiento/genética , Mosaicismo , Deleción CromosómicaRESUMEN
BACKGROUND: Short tandem repeats (STRs) are the most widely used genetic markers in forensic genetics. Therefore, it is essential to document genetic population data of new kits designed for human identification purposes to enable laboratories to use these genetic systems to interpret and solve forensic casework. However, in Mexico, there are no studies with the PowerPlex Fusion 6C System, which includes 26 STRs (23 autosomal STRs and 3 Y-STRs). METHODS AND RESULTS: 600 DNA samples from Mexico City were subjected to genotyping using the PowerPlex Fusion 6C System. For autosomal STRs, 312 different alleles were observed. Combined PE and PD were 99.999999809866% and 99.99999999999999999999999818795%, respectively. Genetic distances and AMOVA test showed low but significant differentiation between Mexican populations. CONCLUSIONS: The results reported in this work demonstrate the efficacy of this system for human identification purposes in the population studied and justify its possible application in other Mexican Mestizo populations.
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Dermatoglifia del ADN , Genética de Población , Humanos , Frecuencia de los Genes/genética , México , Dermatoglifia del ADN/métodos , Repeticiones de Microsatélite/genéticaRESUMEN
Allele frequencies and forensic parameters for 21 STR autosomal markers (CSF1PO, D10S1248, D12S391, D13S317,D16S539, D18S51, D19S433, D1S1656,D21S11, D22S1045, D2S1338, D2S441, D3S1358, D5S818, D7S820, D8S1179, FGA, SE33, TH01, TPOX and vWA) were reported in 289 unrelated individuals from Mexico City, Mexico. In addition, an interpopulation analysis was performed including other world populations. In brief, the established population database of 21 autosomal STR markers in the present work is adequate for human identification purposes.
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Genética de Población , Repeticiones de Microsatélite , Humanos , México , Repeticiones de Microsatélite/genética , Dermatoglifia del ADN , Frecuencia de los GenesRESUMEN
Besides the severe impact on the mortality rate in the world, the COVID-19 pandemic demonstrated the importance of having an optimal physical and mental health, since subjects with chronic diseases were the most affected. The aim of this review was to describe the consequences of nutritional and mental health during the beginning of the pandemic. In developing countries, such as Mexico, the prevalence of mental illnesses including depression, anxiety, stress, and suicide increased considerably. In addition, it was found an increase rate of sedentary lifestyles due to the confinement established as a preventive measure to avoid COVID-19 infections. Concerning eating habits, it was reported a decrease in fruits and vegetables consumption and an increase in energy-dense foods, as well as alcohol consumption or smoking, as compensatory measures for mental disorders of anxiety and depression. Based on the information we look up on the impact of COVID-19 on human health, we suggest as prevention measures multidisciplinary care strategies aimed at promoting mental health, diet, and physical activity habits in a comprehensive context. Likewise, information it is highlighted the importance of establishing care and monitoring programs for patients with chronic diseases, because this factor was decisive for mortality after COVID-19 infection.
Además de su impacto en la tasa de mortalidad en el mundo, la pandemia por COVID-19 demostró la importancia de un estado de salud física y mental óptimo, ya que los sujetos con enfermedades crónicas fueron los más afectados. El objetivo de esta revisión fue describir las consecuencias de la salud nutricional y mental durante los inicios de la pandemia. En los países en vías de desarrollo, como México, la prevalencia de enfermedades mentales como la depresión, la ansiedad, el estrés y los suicidios aumentaron. Además, incrementaron las cifras de sedentarismo debido al confinamiento. Con relación a los hábitos de alimentación, diversos autores reportaron una disminución en el consumo de frutas, verduras, y un aumento de alimentos densamente energéticos, así como el consumo de alcohol o tabaquismo como medidas compensatorias en relación con los trastornos mentales de ansiedad y depresión. A partir de la información consultada en torno al impacto de la COVID-19 en la salud humana, se sugieren como medidas de prevención estrategias de atención multidisciplinaria encaminadas a promover hábitos de salud mental, alimentación y actividad física en un contexto integral. De igual forma, destaca la importancia de establecer programas de atención y monitoreo de pacientes con enfermedades crónicas, debido a que este factor fue determinante para la mortalidad tras la infección por COVID-19.
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COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Pandemias/prevención & control , SARS-CoV-2 , Cuarentena/psicología , HábitosRESUMEN
Population studies regarding Human identification (HID) systems report a priori forensic parameters, but rarely they describe a posteriori parameters from concluded paternity tests. We analyzed data from the PowerPlex® Fusion System in 1503 paternity tests from a Mexican laboratory for five years (2016-2020). The motherless duo paternity tests (89.8%) were more frequent than the standard trio tests (10.2%). A notable increase in motherless tests was noted regarding our previous report (89.8% vs 77.3%), probably explained by the COVID-19 pandemic. The estimated exclusion frequency in Mexico ranged from 30.1 (trio) to 32.1% (duo). For paternity exclusions, we report the number of mismatches and the frequency at which each STR was involved. The PowerPlex® Fusion system showed more than five mismatches in 100% of the standard trio tests excluding paternity, and the majority of motherless-duo tests (98.1%). In positive paternity tests, PowerPlex® Fusion offered a higher combined paternity index (PI) (average 1.18 E + 10) regarding HID systems with 15 and 20 STRs, even without the inclusion of the Y-linked locus DYS391 to the kinship interpretation. Individual and global STR mutation rates were estimated from 17 paternal mutations (µ = 0.0017), the majority involving a single-step mutation (94.11%). Five independent null alleles were detected, most of them involving the Penta E locus (80%), which suggests caution to the users working with DNA databases or kinship analysis, to avoid false exclusions with Penta E. In brief, our results provide a better overview of a posteriori informativeness offered by the PowerPlex® Fusion system for paternity testing in Mexico.
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COVID-19 , Paternidad , Humanos , Frecuencia de los Genes , México , Repeticiones de Microsatélite/genética , PandemiasRESUMEN
Forensic genomic systems allow simultaneously analyzing identity informative (iiSNPs), ancestry informative (aiSNPs), and phenotype informative (piSNPs) genetic markers. Among these kits, the ForenSeq DNA Signature prep (Verogen) analyzes identity STRs and SNPs as well as 24 piSNPs from the HIrisPlex system to predict the hair and eye color. We report herein these 24 piSNPs in 88 samples from Monterrey City (Northeast, Mexico) based on the ForenSeq DNA Signature prep. Phenotypes were predicted by genotype results with both Universal Analysis Software (UAS) and the web tool of the Erasmus Medical Center (EMC). We observed predominantly brown eyes (96.5%) and black hair (75%) phenotypes, whereas blue eyes, and blond and red hair were not observed. Both UAS and EMC showed high performance in eye color prediction (p ≥ 96.6%), but a lower accuracy was observed for hair color prediction. Overall, UAS hair color predictions showed better performance and robustness than those obtained with the EMC web tool (when hair shade is excluded). Although we employed a threshold (p > 70%), we suggest using the EMC enhanced approach to avoid the exclusion of a high number of samples. Finally, although our results are helpful to employ these genomic tools to predict eye color, caution is suggested for hair color prediction in Latin American (admixed) populations such as those studied herein, principally when no black color is predicted.
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Color del Ojo , Color del Cabello , Humanos , Color del Ojo/genética , Color del Cabello/genética , México , Genotipo , ADN/genéticaRESUMEN
BACKGROUND: In the TYMS gene promoter, there is a repeat polymorphism (TSER) that affects the expression level of the thymidylate synthetase (TS) enzyme involved in the response to some anticancer drugs. The G>C transversion located in the TSER*3R allele decreases the expression level of the TS enzyme avoiding the upstream stimulatory factor (USF-1) binding site. Despite the biomedical impact of the SNP G>C, only TSER has been reported in most worldwide populations. Thus, we studied both TSER and SNP G>C variants in the Mexican population. SUBJECTS AND METHODS: A population sample (n = 156) was genotyped for the TSER and G>C variants by PCR and PCR-RFLPs, respectively, followed by PAGE and silver staining. RESULTS: For TSER, the most frequent allele was 2 R (52.56%), as well as the genotype 2 R/3R (42.3%). Comparison with Latin American, European, and American (USA) populations suggest a heterogeneous worldwide distribution (FST-value = 0.01564; p-value = 0.0000). When the G>C variant was included (2RG, 3RG, and 3RC), a high frequency of low expression genotypes was observed: 2RG/2RG, 2RG/3RC, and 3RC/3RC (84.6%). CONCLUSION: The high frequency of genotypes associated with low TS enzyme expression justifies obtaining the TYMS gene variant profile in Mexican patient's candidates to pharmaceutical treatments like 5'-Fluoracil, methotrexate, and pemetrex.
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Fluorouracilo , Polimorfismo Genético , Timidilato Sintasa , Humanos , Alelos , Genotipo , Polimorfismo de Longitud del Fragmento de Restricción , Timidilato Sintasa/genética , Timidilato Sintasa/metabolismo , MéxicoRESUMEN
Few studies have addressed how selective pressures have shaped the genetic structure of the current Native American populations, and they have mostly limited their inferences to admixed Latin American populations. Here, we searched for local adaptation signals, based on integrated haplotype scores and population branch statistics, in 325 Mexican Indigenous individuals with at least 99% Native American ancestry from five previously defined geographical regions. Although each region exhibited its own local adaptation profile, only PPARG and AJAP1, both negative regulators of the Wnt/ß catenin signaling pathway, showed significant adaptation signals in all the tested regions. Several signals were found, mainly in the genes related to the metabolic processes and immune response. A pathway enrichment analysis revealed the overrepresentation of selected genes related to several biological phenotypes/conditions, such as the immune response and metabolic pathways, in agreement with previous studies, suggesting that immunological and metabolic pressures are major drivers of human adaptation. Genes related to the gut microbiome measurements were overrepresented in all the regions, highlighting the importance of studying how humans have coevolved with the microbial communities that colonize them. Our results provide a further explanation of the human evolutionary history in response to environmental pressures in this region.
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Adaptación Fisiológica , Indio Americano o Nativo de Alaska , Humanos , México , Adaptación Fisiológica/genética , Hispánicos o Latinos , Grupos RacialesRESUMEN
BACKGROUND: STR allele frequency databases from populations are necessary to take full advantage of the increased power of discrimination offered by massively parallel sequencing (MPS) platforms. MATERIAL AND METHODS: For this reason, we sequenced 58 STRs (aSTRs, X-STRs, and Y-STRs) and 94 identity informative SNPs (iiSNPs) on 105 Mestizo (admixed) individuals from Monterrey City (Northeast, Mexico), with the Primer Set-A of the ForenSeq™ DNA Signature Prep Kit. RESULTS: Most of the STR markers were in Hardy Weinberg equilibrium, with a few exceptions. We found 346 different length-based alleles for these 58 STRs; nevertheless, they became 528 alleles when the sequence was assessed. The combined power of discrimination from autosomal STRs (aSTRs) was -virtually- 100% in both length and sequence-based alleles, while the power of exclusion was 99.9999999976065 and 99.9999999999494%, respectively. Haplotypes based on X-STRs and Y-STRs showed 100% of discriminatory capacity. CONCLUSIONS: These results provide -for the first time- forensic genomic population data from Mexico necessary for interpretation in kinship and criminal analyses.
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Dermatoglifia del ADN , Polimorfismo de Nucleótido Simple , ADN , Frecuencia de los Genes/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , México , Repeticiones de Microsatélite/genética , Polimorfismo de Nucleótido Simple/genética , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: Mexican population databases for autosomal STRs are scarce, and no previous studies have been performed with the Qiagen Investigator 24plex GO! AIM: To analyse the frequency of 21 autosomal short tandem repeat (STR) loci and forensic parameters in individuals from Veracruz state, Mexico. SUBJECTS AND METHODS: A total of 234 unrelated individuals were analysed with the Investigator 24plex GO! Kit, which includes the following autosomal STRs: TH01, D3S1358, vWA, D21S11, TPOX, D1S1656, D12S391, SE33, D10S1248, D22S1045, D19S433, D8S133879, D2S1338, D2S441, D18S51, FGA, D16S539, CSF1PO, D13S317, D5S818, and D7S820. Allele frequencies, forensic parameters, and relationships with neighbouring Mexican populations were estimated. RESULTS: The STRs analysed were in Hardy-Weinberg Equilibrium (HWE). The combined matching probability and combined PE were 1.5266 E-24 and 0.999999988711, respectively. The D18S51 and SE33 loci presented the highest Ho (0.8974 and 0.8932) and PE (0.7902 and 0.7815), respectively. The highest PIC (0.9337) and PD (0.9894) values corresponded to SE33. Conversely, D22S1045 had the lowest PIC and PE (0.5533 and 0.3546, respectively). A population cluster among southern Mexican populations, which included non-differentiation between Guerrero and Veracruz states was detected. CONCLUSION: The forensic efficacy of the 21 STRs analysed by the Investigator 24plex GO! Kit was evaluated in the Veracruz state. Moreover, new population clusters that have not yet been described and are related to geographic regions were identified, and these are in agreement with previously reported ancestral differences.
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Genética de Población , Repeticiones de Microsatélite , Frecuencia de los Genes , Humanos , México , Repeticiones de Microsatélite/genéticaRESUMEN
Native American genetic ancestry has been remarkably implicated with increased risk of diverse health issues in several Mexican populations, especially in relation to the dramatic changes in environmental, dietary, and cultural settings they have recently undergone. In particular, the effects of these ecological transitions and Westernization of lifestyles have been investigated so far predominantly on Mestizo individuals. Nevertheless, indigenous groups, rather than admixed Mexicans, have plausibly retained the highest proportions of genetic components shaped by natural selection in response to the ancient milieu experienced by Mexican ancestors during their pre-Columbian evolutionary history. These formerly adaptive variants have the potential to represent the genetic determinants of some biological traits that are peculiar to Mexican people, as well as a reservoir of loci with possible biomedical relevance. To test such a hypothesis, we used genome-wide genotype data to infer the unique adaptive evolution of Native Mexican groups selected as reasonable descendants of the main pre-Columbian Mexican civilizations. A combination of haplotype-based and gene-network analyses enabled us to detect genomic signatures ascribable to polygenic adaptive traits plausibly evolved by the main genetic clusters of Mexican indigenous populations to cope with local environmental and/or cultural conditions. Some of these adaptations were found to play a role in modulating the susceptibility/resistance of these groups to certain pathological conditions, thus providing new evidence that diverse selective pressures have contributed to shape the current biological and disease-risk patterns of present-day Native and Mestizo Mexican populations.
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Adaptación Fisiológica , Selección Genética , Genotipo , Haplotipos , Humanos , Herencia MultifactorialRESUMEN
Aim: To evaluate the genetic distribution of the rs4149056 and rs2306283 variants in the SLCO1B1 gene in Mexican Mestizo (admixed) and Native American groups. Materials & methods: We recruited 360 volunteers who were qPCR-genotyped with TaqMan probes. Results: Allele and genotype frequencies are reported. Among the expected rs4149056-rs2306283 haplotypes, T-A (42.35-58.47%) was the most prevalent which relates to the normal activity of the OATP1B1 transporter. This was followed by the T-G haplotype associated with further statin transport and cholesterol reduction (32.49-43.76%). Conclusion: Based on these SLCO1B1 gene variants, we confirmed that a minimum fraction of the Mexican study populations would be at risk from decreasing simvastatin transport and the development of statin-induced myopathy.
Lay abstract The clinical response to statins, mainly atorvastatin and simvastatin, can be modified by interindividual variability including variations in the SLCO1B1 gene. This gene, that encodes the statin transporter OATP1B1, helps to regulate the cholesterol levels in the blood and is responsible for the presence of adverse drug reactions related to the statin consumption, such as muscular sickness. This study analyzes the distribution of the SLCO1B1 gene variants rs4149056 and rs2306283 in geographically dispersed samples of the two main populations in Mexico: two Mestizo (admixed) populations and three Native American groups. We found that the genetic combinations of TA and TG for the two SLCO1B1 gene variants associated with normal or efficient activity of the transporter OATP1B were predominant in all of the study population. Therefore, the SLCO1B1 gene variability suggests that a majority of the Mexican population will respond favorably to simvastatin and have a low risk of developing associated muscular complications.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas , Enfermedades Musculares , Haplotipos/genética , Humanos , Transportador 1 de Anión Orgánico Específico del Hígado/genética , Polimorfismo de Nucleótido Simple/genética , PrevalenciaRESUMEN
The genetic makeup of Indigenous populations inhabiting Mexico has been strongly influenced by geography and demographic history. Here, we perform a genome-wide analysis of 716 newly genotyped individuals from 60 of the 68 recognized ethnic groups in Mexico. We show that the genetic structure of these populations is strongly influenced by geography, and our demographic reconstructions suggest a decline in the population size of all tested populations in the last 15-30 generations. We find evidence that Aridoamerican and Mesoamerican populations diverged roughly 4-9.9 ka, around the time when sedentary farming started in Mesoamerica. Comparisons with ancient genomes indicate that the Upward Sun River 1 (USR1) individual is an outgroup to Mexican/South American Indigenous populations, whereas Anzick-1 was more closely related to Mesoamerican/South American populations than to those from Aridoamerica, showing an even more complex history of divergence than recognized so far.
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Etnicidad/genética , Genoma Humano , Migración Humana/historia , Indígenas Norteamericanos/genética , Filogenia , Dinámica Poblacional/estadística & datos numéricos , Etnicidad/clasificación , Variación Genética , Genómica/métodos , Historia Antigua , Humanos , Indígenas Norteamericanos/clasificación , México , FilogeografíaRESUMEN
BACKGROUND: MATE2-K is an efflux transporter protein of organic cation expressed mainly in the kidney and encoded by the SLC47A2 gene. Different variants of this gene have shown an impact on the pharmacokinetics of various drugs, including metformin, which represents one of the most widely used drugs in treating type 2 diabetes. The SLC47A2 gene variants have been scarcely studied in Mexican populations, especially in Native American groups. For this reason, we analyzed the distribution of the variants rs12943590, rs35263947, and rs9900497 within the SLC47A2 gene in 173 Native Americans (Tarahumara, Huichol, Maya, Puerépecha) and 182 Mestizos (admixed) individuals from Mexico. METHODS AND RESULTS: Genotypes were determined through TaqMan probes (qPCR). The Hardy-Weinberg agreement was confirmed for all three SLC47A2 gene variants in all the Mexican populations analyzed. When worldwide populations were included for comparison purposes, for alleles and genotypes a relative interpopulation homogeneity was observed for rs35263947 (T allele; range 23.3-51.1%) and rs9900497 (T allele; range 18.6-40.9%). Conversely, heterogeneity was evident for rs12943590 (A allele, range 22.1-59.1%), where the most differentiated population was the Huichol, with high frequencies of the risk genotype associated with decreased response to metformin treatment (A/A = 40.9%). CONCLUSIONS: Although the SLC47A2 gene variants allow predicting favorable response to the metformin treatment in Mexican populations, the probable high frequency of ineffectiveness should be discarded in Huichols.
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Indio Americano o Nativo de Alaska/genética , Genética de Población/métodos , Indígenas Norteamericanos/genética , Proteínas de Transporte de Catión Orgánico/genética , Polimorfismo de Nucleótido Simple , Alelos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Frecuencia de los Genes , Haplotipos , Voluntarios Sanos , Humanos , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , México/etnología , Plantas Medicinales , Resultado del TratamientoRESUMEN
ABSTRACT Background: Early-onset diffuse gastric cancer (EODGC) occurs at or before 50 years of age. Pathogenic mutations and germline deletions in the CDH1 gene (E-cadherin) are well-documented genetic factors associated with the causes of EODGC. Objective: The objective of the study was to study CDH1 germline variants and their potential functional impact in patients with EODGC in a Mexican population. Methods: We studied seven EODGC patients from a biomedical research center in western Mexico. Variants were identified by Sanger sequencing and multiplex ligation-dependent probe amplification. The DeepSEA and SNPClinic v.1.0 software and the Ensembl (1000 Genomes Project, 1kGP) and ClinVar databases were used to predict functional single-nucleotide polymorphisms (SNPs). The genetic admixture of the Mexican patients was corroborated by 22 short tandem repeat loci genotyping and structure analysis. Results: We found 12 germline CDH1 variants in all EODGC patients, and all of them are considered as polymorphisms: rs34561447, rs5030625, rs16260, rs1330727101, rs28372783, rs942269593, rs3743674, rs1801552, rs34939176, rs33964119, rs3556654, and rs1801026. The prediction of regulatory SNPs in the promoter suggests a role for a retrovirus in EODGC that induces the transcription of interferon-related genes through toll-like receptor-interferon response factor 3 signaling, as three SNPs in the CDH1 promoter alter three binding sites for this transcription factor. In addition, SNPs rs28372783 and rs1801026 could alter upstream stimulatory factors 1 (USF1)/USF2-mediated telomerase-dependent lymphocyte activation in EODGC. Other interesting result is a CTCF-dependent shorter CDH1 isoform lacking exon 14, probably due to exon-skipping mediated by rs33964119. Conclusions: Classical pathogenic germline mutations in the CDH1 gene were not found in these 7 EODGC patients. However, the in silico approaches revealed the possible involvement of a retrovirus and a shorter E-cadherin isoform in EODGC. Nevertheless, further in vitro and in vivo assays are needed to confirm these predictions.
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OBJECTIVE: To analyze the genetic origin, relationships, structure, and admixture in Mayan Native American groups from Guatemala and Mexico based on 15 autosomal short tandem repeats (STRs) loci commonly used in human identification (HID). METHODS: We genotyped 513 unrelated Mayan samples from Guatemala based on 15 STR loci (AmpFlSTR® Identifiler kit). Moreover, we included 4408 genotypes previously reported, as following: Mayas from Guatemala and Mexico (n = 1666) and from Latin American, European, and African (n = 2742) populations. Forensic parameters, genetic distances, admixture, and population structure were assessed. RESULTS: Forensic parameters of the 15 STRs in different Mayan groups from Guatemala were reported. Low (Fst = 0.78%; p = 0.000) and non-significant differentiation (Fst = 1.8%; p = 0.108) were observed in Mayas from Guatemala and Mexico, respectively. The relative homogeneity observed among Mayan groups supported theories of extensive pre-Columbian gene flow and trade throughout the Mayan Empire. The distribution of the three Native American ancestries among these Mayan groups did not support the presumable Guatemalan origin of Tojolabal and Lacandon people (South, Mexico). The nonsignificant differentiation between Ladinos and Mayas suggests a relative panmixia in Guatemala. Mestizos from southeastern Mexico and Guatemala constitute a core of Native American ancestry in Latin America related to the Mayan Empire in Central America. CONCLUSIONS: The higher European admixture and homogeneity in Mexican Mayas of the Yucatan Peninsula suggest more intensive post-Columbian gene flow in this region than in Guatemalan Mayas.
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Variación Genética/genética , Indígenas Centroamericanos/genética , Indígenas Norteamericanos/genética , Repeticiones de Microsatélite/genética , Antropología Física , Genética Forense , Flujo Génico/genética , Genética de Población , Guatemala , Humanos , México , Población Blanca/genéticaRESUMEN
BACKGROUND: Early-onset diffuse gastric cancer (EODGC) occurs at or before 50 years of age. Pathogenic mutations and germline deletions in the CDH1 gene (E-cadherin) are well-documented genetic factors associated with the causes of EODGC. OBJECTIVE: The objective of the study was to study CDH1 germline variants and their potential functional impact in patients with EODGC in a Mexican population. METHODS: We studied seven EODGC patients from a biomedical research center in western Mexico. Variants were identified by Sanger sequencing and multiplex ligation-dependent probe amplification. The DeepSEA and SNPClinic v.1.0 software and the Ensembl (1000 Genomes Project, 1kGP) and ClinVar databases were used to predict functional single-nucleotide polymorphisms (SNPs). The genetic admixture of the Mexican patients was corroborated by 22 short tandem repeat loci genotyping and structure analysis. RESULTS: We found 12 germline CDH1 variants in all EODGC patients, and all of them are considered as polymorphisms: rs34561447, rs5030625, rs16260, rs1330727101, rs28372783, rs942269593, rs3743674, rs1801552, rs34939176, rs33964119, rs3556654, and rs1801026. The prediction of regulatory SNPs in the promoter suggests a role for a retrovirus in EODGC that induces the transcription of interferon-related genes through toll-like receptor-interferon response factor 3 signaling, as three SNPs in the CDH1 promoter alter three binding sites for this transcription factor. In addition, SNPs rs28372783 and rs1801026 could alter upstream stimulatory factors 1 (USF1)/USF2-mediated telomerase-dependent lymphocyte activation in EODGC. Other interesting result is a CTCF-dependent shorter CDH1 isoform lacking exon 14, probably due to exon-skipping mediated by rs33964119. CONCLUSIONS: Classical pathogenic germline mutations in the CDH1 gene were not found in these 7 EODGC patients. However, the in silico approaches revealed the possible involvement of a retrovirus and a shorter E-cadherin isoform in EODGC. Nevertheless, further in vitro and in vivo assays are needed to confirm these predictions.
RESUMEN
Aims: The 5HTT gene has been associated with obesity; this study aimed to determine the association between L- and S-alleles at the 5HTTLPR polymorphism with obesity in indigenous Mexican populations. Materials and Methods: A total of 362 individuals, 289 belonging to eight Native American (NA) groups; 40 Mexican mestizos; and 33 Caucasian Mennonites were enrolled in a cross-sectional study. High (≥90%) and low (<90%) NA ancestry was molecularly determined. A body mass index >30 kg/m2 was considered as obese. The L- and S-alleles of the 5HTTLPR locus were identified by PCR; the association between alleles and obesity was performed by logistic regression analysis. Results: A significantly lower prevalence of obesity (35%) was observed in participants from communities with high NA ancestry (p < 0.005). Under a dominant heritance model the L-allele was associated with obesity in women with high NA ancestry (odds ratio [OR] 7.27; 95% confidence interval [CI] 1.6-32.5; p = 0.009) but not in women with low NA ancestry (OR 0.83; 95% CI 0.3-2.2; p = 0.71); no association was observed in men. Conclusion: Our results suggest that the 5HTTLPR L-allele is a risk factor for developing obesity in Mexican women with high NA ancestry (≥90%).