Multiple sclerosis in Central America and Caribbean countries: frequency and clinical characterization of an emergent disease.

Background: Multiple Sclerosis (MS) is a common neurological disease among white populations of European origin. Frequencies among Latin Americans continue to be studied, however, epidemiologic, and clinical characterization studies lack from Central American and Caribbean countries. Ethnicity in these countries is uniformly similar with a prevalent Mestizo population. Methods and results: Data from January 2014 to December 2019 from Guatemala, El Salvador, Honduras, Nicaragua, Costa Rica, Panama, Dominican Republic, and Aruba on demographic, clinical, MRI and phenotypic traits were determined in coordinated studies: ENHANCE, a population-based, retrospective, observational study on incidence and clinical characteristics, and from the subgroup with MS national registries (Aruba, Dominican Republic, Honduras, and Panama), data on prevalence, phenotypes and demographics. Expanded Disability Status Scale (EDSS), and therapeutic schemes were included. ENHANCE data from 758 patients disclosed 79.8% of Mestizo ethnicity; 72.4% female; median age at onset 31.0 years and 33.2 at diagnosis. The highest incidence rate was from Aruba, 2.3-3.5 × 100,000 inhabitants, and the lowest, 0.07-0.15 × 100,000, from Honduras. Crude prevalence rates per 100,000 inhabitants fluctuated from 27.3 (Aruba) to 1.0 (Honduras). Relapsing MS accounted for 87.4% of cases; EDSS <3.0 determined in 66.6% (mean disease duration: 9.1 years, SD ± 5.0); CSF oligoclonal bands 85.7%, and 87% of subjects hydroxyvitamin D deficient. Common initial therapies were interferon and fingolimod. Switching from interferon to fingolimod was the most common escalation step. The COVID-19 pandemic affected follow-up aspects of these studies. Conclusion: This is the first study providing data on frequencies and clinical characteristics from 8 countries from the Central American and Caribbean region, addressing MS as an emergent epidemiologic disorder. More studies from these areas are encouraged.

Honduras HIV cohort: HLA class I and CCR5-Δ32 profiles and their associations with HIV disease outcome.

IMPORTANCE: We identify both canonical and novel human leukocyte antigen (HLA)-HIV associations, providing a first step toward improved understanding of HIV immune control among the understudied Honduras Mestizo population. Our results are relevant to understanding the protective or detrimental effects of HLA subtypes in Latin America because their unique HLA diversity poses challenges for designing vaccines against HIV and interpreting results from such vaccine trials. Likewise, the description of the HLA profile in an understudied population that shows a unique HLA immunogenetic background is not only relevant for HIV immunology but also relevant in population genetics, molecular anthropology, susceptibility to other infections, autoimmune diseases, and allograft transplantation.

Genotyping NUDT15*3 rs1166855232 reveals higher frequency of potential adverse effects of thiopurines in Natives and Mestizos from Mexico.

BACKGROUND: Thiopurines are effectively prescribed for immune and oncology diseases but their toxicity leads to severe myelosuppression. Therefore, TPMT genetic variants have been used to adjust dosing for poor and intermediate metabolizers, significantly preventing adverse drug reactions. In 2018, the Clinical Pharmacogenetics Implementation Consortium included NUDT15 rs116855232 to also guide thiopurines dosing. This variant is not present in Caucasians but have been identified in 10% of Asian and Latin American populations. Despite research efforts to portrait the world's genetic variation, few studies include the investigation of NUDT15 in large samples. METHODS: Fifteen NUDT15 and TPMT variants were retrieved for 1270 Mestizos and 20 Natives genotyped from previous studies using the GSA-Illumina microarray. After bioinformatic quality controls, genotypes were available for 12 variants, TPMT rs2842949, rs2842950, rs2842934, rs1800460, rs12201199, rs12663332, rs2518463, rs4449636, rs12529220, rs3931660, rs200591577, and NUD15 rs116855232. Allele frequencies and haplotypes were assessed using PLINK, R, and Haploview. Dosing inferences were described according to the Clinical Pharmacogenomics Implementation Consortium. RESULTS: We report relevant populations differences in actionable TPMT*3B and NUDT15 rs116855232 as the allele frequency of the former is higher in Mestizos compared to Caucasians, and for the latter we report twofold and 1.35-fold higher allele frequencies in Natives and Mestizos compared to Mexicans from Los Angeles. CONCLUSIONS: TPMT*3B and NUDT15 rs116855232 actionable markers showed population differences that ought to be considered as dosing inferences highlight the relevance of routine genotyping of these variants for the prescription of thiopurines in Mexican populations.

Population diversity of three variants of the SLC47A2 gene (MATE2-K transporter) in Mexican Mestizos and Native Americans.

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.

Maternal and Perinatal Factors Associated With Twin Pregnancies in Ecuador.

There are few studies on twins in Ecuador and Latin America. It requires a better understanding of perinatal conditions, especially from an ethnic perspective. This work aims to assess perinatal factors related to twin pregnancy in Ecuadorian Mestizo individuals. We performed an epidemiological, observational and cross-sectional study at the Hospital San Francisco and Hospital Nueva Aurora in Quito, Ecuador, from November 2019 to January 2020. It included 203 newborns from twin pregnancies, including mothers with and without pathological history. The average gestational age was 31 weeks, and the APGAR score at first minute was 6.86, with significant differences. Regarding the metabolic balance, the mean pH was 6.14; and bicarbonate was 11.57, with significant differences. Twins had intrauterine growth restriction in 6.9% of cases, with significant differences (p = .003); 81.4% required supplemental oxygen, with significant differences (p = .002); 93% required noninvasive mechanical ventilation (NIMV), with significant differences (p = . 003); 93% required inotropic and sedation, with substantial differences; 69% required antibiotics (≥21 days), with significant differences (p = .014); and 17.2% needed between 8 to 14 days of hospitalization, and 51% more than 28 days, with significant differences. The studied mothers' demographic profile was mostly Mestizos, with an average age of 32 years, and 93% had a poverty status. Most of the twins were diamniotic monochorial and were discordant twins. It found jaundice, premature anemia and sepsis in 100% of twins and hyaline membrane disease in 89.66% of twins. Twins of women with relevant prenatal care had more premature births (30.4 ± 2.6 weeks), more acid-base imbalance, APGAR at ≥7 min in 90% of cases, and patent ductus arteriosus in all. There was also a greater need for double intensive phototherapy than twins of healthy women.

Mayan alleles of the HLA-DRB1 major histocompatibility complex might contribute to the genetic susceptibility to systemic lupus erythematosus in Mexican patients from Tapachula, Chiapas.

INTRODUCTION: Systemic lupus erythematosus (SLE) is the prototypic autoimmune disease that disrupts numerous immunity mechanisms with the potential to exert damage to any organ or tissue. Its etiology remains uncertain; however, genetic and environmental factors that differ between populations strongly influence its development. Among the physiopathogenic factors, the genetic ones predominate, notably the major histocompatibility complex (MHC) loci. A high degree of ethnical admixture makes Mexican Mestizos a thoroughly genetically heterogeneous population. Therefore, this study aimed to identify the MHC polymorphisms associated with SLE development in Mexican Mestizos from Southern Mexico and compare them with patients from Mexico City. METHOD: A transversal study in SLE patients from Tapachula, Chiapas, was conducted. DNA typing of human leukocyte antigens (HLA) classes I and II was performed using single specific primers (SSP). Admixture analysis was performed using the population genetics LEADMIX software. RESULTS: The frequencies of HLA-DRB1*16 and HLA-DQB1*05 were found to have a tendency towards increase in SLE patients, compared to ethnically matched healthy controls. The allele HLA-DRB1*03 seemed to be less associated with SLE in this group of Mexican Mestizos, opposed to other more Caucasian populations. Admixture analysis showed a higher Mayan genetic component in these patients from Chiapas. CONCLUSIONS: The genetic susceptibility for SLE differed in two populations of Mexican Mestizos with dissimilar ethnic ancestries. Autochthonous Amerindian alleles, and not the more widely known Caucasian alleles, might be associated with the susceptibility to SLE in Mexican Mestizos from Tapachula, Chiapas. Key Points • Autochthonous Amerindian alleles, such as HLA-DRB1*16, had a tendency to be increased in SLE patients, compared to healthy controls. • SLE susceptibility alleles vary considerably among regions in Mexico, according to the distribution of the indigenous groups. • Ethnic admixture is a key determinant in the genetic susceptibility of SLE.

High prevalence of CYP2D6 ultrarapid metabolizers in a mestizo Colombian population in relation to Hispanic mestizo populations.

Background: Interethnic differences in CYP2D6 allele frequency have been demonstrated across Latin-American countries. Only one previous study describing CYP2D6 genotypes in Colombian population has been performed. Thus, this study aimed to evaluate the CYP2D6 genetic variability in a mestizo Colombian population, as well as the similarities and differences concerning other Hispanic mestizo (HM) populations. Methodology: Two hundred and twelve unrelated healthy Colombian subjects were studied, in which different CYP2D6 polymorphisms were analyzed by extra long-PCR and real-time PCR. Results & discussion: A high percentage of ultrarapid metabolizers (18.4%) was found, representing the highest frequency calculated within the HM populations studied. However, the percentage of poor metabolizers (4.7%) was similar to those previously reported in HM populations.

Genotype-Environment Interaction Analysis of NQO1, CYP2E1, and NAT2 Polymorphisms and the Risk of Childhood Acute Lymphoblastic Leukemia: A Report From the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia.

Background: Acute lymphoblastic leukemia (ALL) is the main type of cancer in children. In Mexico and other Hispanic populations, the incidence of this neoplasm is one of the highest reported worldwide. Functional polymorphisms of various enzymes involved in the metabolism of xenobiotics have been associated with an increased risk of developing ALL, and the risk is different by ethnicity. The aims of the present study were to identify whether NQO1, CYP2E1, and NAT2 polymorphisms or some genotype-environmental interactions were associated with ALL risk in Mexican children. Methods: We conducted a case-control study including 478 pediatric patients diagnosed with ALL and 284 controls (children without leukemia). Ancestry composition of a subset of cases and controls was assessed using 32 ancestry informative markers. Genetic-environmental interactions for the exposure to hydrocarbons were assessed by logistic regression analysis. Results: The polymorphisms rs1801280 (OR 1.54, 95% CI 1.21-1.93), rs1799929 (OR 1.96, 95% CI 1.55-2.49), and rs1208 (OR 1.44, 95% CI 1.14-1.81) were found to increase the risk of ALL; being the risks higher under a recessive model (OR 2.20, 95% CI 1.30-1.71, OR 3.87, 95% CI 2.20-6.80, and OR 2.26, 95% CI 1.32-3.87, respectively). Gene-environment interaction analysis showed that NAT2 rs1799929 TT genotype confers high risk to ALL under exposure to fertilizers, insecticides, hydrocarbon derivatives, and parental tobacco smoking. No associations among NQO1, CYP2E1, and ALL were observed. Conclusion: Our study provides evidence for the association between NAT2 polymorphisms/gene-environment interactions, and the risk of childhood ALL in Mexican children.

Pharmacogenomics: Current Actionable Variants

Pharmacogenomics (PGx), one of the several tools of precision medicine, has been slowly implemented in the clinic during the past decades. This process generally starts with direct and indirect genotype-phenotype associations of gene variants and drug efficacy, or adverse drug reactions, followed by replication and validation studies. Institutional efforts led by the PGx Research Network, The PGx Knowledge Base, and The Clinical Pharmacogenetics Implementation Consortium, mine all available data for further validation or research in additional populations. This data mining gives rise to a detailed classification of over 200 drug-gene pairs which, with enough documentation, may become part of a publishable guideline to aid clinicians in drug selection and dosing using genetics. The US Food and Drug Administration utilizes these guidelines to issue warnings and recommendations for specific drugs and their cautioning serves clinicians and pharmacists worldwide. Here, we aim to discuss the steps of this process and list existing actionable drug-gene pairs. Moreover, we describe the current status of PGx knowledge in populations from Mexico for actionable variants on the 19 genes listed by present PGx guidelines affecting 47 drugs. Our review collects current allele frequency information for these actionable variants, lists gaps of PGx information for relevant markers, and highlights the importance of continuing PGx research in Native and Mestizo populations. (REV INVEST CLIN. 2020;72(5):271-9)

Blood Pressure in Andean Adults Living Permanently at Different Altitudes.

Vinueza Veloz, Andrés Fernando, Aymaru Kailli Yaulema Riss, Chris I. De Zeeuw, Tannia Valeria Carpio Arias, and María Fernanda Vinueza Veloz. Blood pressure in Andean adults living permanently at different altitudes. High Alt Med Biol. 21:360-369, 2020. Aims: To estimate the association between blood pressure (BP) and chronic exposure to altitude in nonhypertensive Andean adults, while taking ethnicity into consideration. Materials and Methods: Sample included 10,041 nonhypertensive adults with indigenous or mixed ethnic background (the latter also referred to as mestizos), who permanently lived at different altitudes. BP was measured following international recommendations. Altitude was measured in meters above the sea level (masl) using a global positioning system. Data were analyzed through linear regression models with restricted cubic splines. Results: A significant nonlinear relation between altitude and systolic blood pressure (SBP) as well as diastolic blood pressure (DBP) was found (both p < 0.001). BP described a j-shaped curve, where the minimum was observed between 750 and 1250 masl, from where both SBP and DBP rose as altitude increased. These associations were independent from sex, age, index of economic wellbeing, body mass index, and years of education. Interestingly, at all altitudes indigenous people had lower SBP and DBP in comparison to mestizos (both p < 0.001). Conclusions: Living permanently at altitudes ≥750 masl is associated with higher SBP and DBP in Andean dwellers and this association is modulated by their ethnic background.

Endoxifen levels and metabolic phenotype-associated factors in Mexican Mestizo patients under tamoxifen treatment.

Aim: To evaluate plasma endoxifen levels and metabolic phenotype-associated factors in Mexican Mestizo patients under tamoxifen treatment. Patients & methods: A total of 138 breast cancer patients under tamoxifen treatment were cross-sectionally evaluated and side effects (SE) were recorded. CYP2D6 genetic phenotypes (GP) and metabolic phenotypes (MP) were assessed (metabolic poor [mPM], intermediate [mIM], normal [mNM], and ultrarapid [mUM] metabolizer). Associations were tested in uni-multivariate models for endoxifen >5.9 ng/ml and for mNM + mUM MP. Results: The main SE was hot flashes (62%). Distribution of the CYP2D6 MP was 4.3% mPM; 14.5% mIM; 75.4% mNM; and 5.8% mUM. Endoxifen >5.9 ng/ml was partially associated with SE (p = 0.06); the mNM + mUM MP was associated with treatment time (p = 0.03). Conclusion: The endoxifen-associated factors in Mexican Mestizo patients remain inconclusive, although treatment time was associated with MP.

CYP2D6 does not impact on breast cancer-free survival in Southeast Mexican patients under tamoxifen treatment.

Aim: We conducted a retrospective analysis in 71 Mexican Mestizo patients to evaluate the breast cancer-free survival (BCFS) among the inferred genetic phenotypes (GP) of CYP2D6. Patients & methods:CYP2D6 was genotyped through Taqman-probe analysis; GP were inferred according to international guidelines. The BCFS was estimated through Kaplan-Meier method and analyzed with a log-rank test; hazard ratios were calculated with 95% CI and p < 0.05. Results: The BCFS did not differ among CYP2D6 GP (p = 0.45) and recurrence risk was similar between gNM + gUM and gPM + gIM groups (hazard ratio: 1.54, 95% CI: 0.37-6.38; p = 0.55). Conclusion: The findings do not support any impact of CYP2D6 on BCFS. Evaluation of other genetic/nongenetic biomarkers is needed in Mexican Mestizo patients under tamoxifen treatment.

Paternal lineages and forensic parameters based on 23 Y-STRs (Powerplex® Y23) in Mestizo males from Mexico City.

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

Eugenics, Epigenetics, and Obesity Predisposition among Mexican Mestizos.

We compare the discourses on obesity found in early- and mid-twentieth century Mexican public discourse with those of Mexican geneticists and doctors today. We argue that postgenomic shifts towards non-determinism, apparently contained in current openness to epigenetics, need to be considered alongside the persistence of racialized genetic determinisms, and alongside the potential for epigenetic environmental determinisms. By exploring the environmentalist explanations of earlier eugenic thinking about obesity, we trace continuities in the gendered and racialized framings of obesity, which risk stigmatizing indigenous ancestry and attributing blame to individual mothers.

Exploring the ancestry and admixture of Mexican Oaxaca Mestizos from Southeast Mexico using next-generation sequencing of 11 HLA loci.

The Mestizos of Oaxaca resulted from the admixture of Zapotecan Natives with Spaniards and Africans. We selected 112 donors from Oaxaca and applied next-generation sequencing to characterize exon and intron variants in complete or extended HLA genes. Some alleles found, are unique to Mexican Natives and most likely will be absent in most major ethnicities, namely: Caucasians, Africans or Asians. Among these are HLA-A*68:03:01, HLA-A*68:05:01, HLA-C*03:04:01:02, HLA-C*15:09, HLA-C*3:05, HLA-C*03:06:01, HLA-B*39:05:01, HLA-B*35:14:01, HLA-B*35:12:01, HLA-B*35:43:01, HLA-B*40:05, HLA-B:40:08, HLA-B*51:02:01, HLA-B*35:24:01 and HLA-B*39:08. HLA-DQA1*05:05:01:05 and some HLA-DRB1 alleles were only present in Amerindians/Mestizos. Three haplotypes are unique to Mexican Natives, five to Middle-Eastern and Sephardi-Jews. We detected a novel HLA-DQA1*04:01:01 exon 4 variant. Any novel allele may have been positively selected to enlarge the peptide-binding repertoire, and some, like HLA-B*39:02:02 and HLA-B*39:05:01 were found with unique haplotype associations, suggesting convergent evolution events and/or allele lineage diversification. The allele frequencies were fairly evenly distributed in most HLA loci with the exception of HLA-DPB1. The application of NGS in Oaxaca is novel and will lead to better use in the clinical setting. It offers deep knowledge on the population structure, origins, migration, and discovery of new alleles and haplotypes that other techniques did not achieve.

Forensic parameters of 15 autosomal STRs (Identifiler™ kit) in three Mayan groups and one Mestizo population from Guatemala.

The population of Guatemala includes Mestizos (admixed) and different Mayan groups (Native Americans), which have been poorly studied in regards to short tandem repeat (STR) loci used for human identification (HID) purposes. Therefore, 483 unrelated Guatemalan volunteers from one Mestizo and three Mayan populations (Poqomchi, Ixil, and Achi) were analyzed with an AmpFlSTR Identifiler™ kit. Allele frequencies and forensic parameters were obtained for 15 autosomal STRs in these populations. Hardy-Weinberg equilibrium by locus and equilibrium linkage between pair of loci were demonstrated by exact tests in all the studied populations. Larger genetic differentiation probably due to genetic drift effects was observed among the studied Guatemalan Mayan groups than the neighboring Mexican Mayas. In brief, our results validate to use the Identifiler™ kit for HID in three non-previously studied Mayan groups, and one Mestizo population from Guatemala.

A panel of 32 AIMs suitable for population stratification correction and global ancestry estimation in Mexican mestizos.

BACKGROUND: Association studies are useful to unravel the genetic basis of common human diseases. However, the presence of undetected population structure can lead to both false positive results and failures to detect genuine associations. Even when most of the approaches to deal with population stratification require genome-wide data, the use of a well-selected panel of ancestry informative markers (AIMs) may appropriately correct for population stratification. Few panels of AIMs have been developed for Latino populations and most contain a high number of markers (> 100 AIMs). For some association studies such as candidate gene approaches, it may be unfeasible to genotype a numerous set of markers to avoid false positive results. In such cases, methods that use fewer AIMs may be appropriate. RESULTS: We validated an accurate and cost-effective panel of AIMs, for use in population stratification correction of association studies and global ancestry estimation in Mexicans, as well as in populations having large proportions of both European and Native American ancestries. Based on genome-wide data from 1953 Mexican individuals, we performed a PCA and SNP weights were calculated to select subsets of unlinked AIMs within percentiles 0.10 and 0.90, ensuring that all chromosomes were represented. Correlations between PC1 calculated using genome-wide data versus each subset of AIMs (16, 32, 48 and 64) were r2 = 0.923, 0.959, 0.972 and 0.978, respectively. When evaluating PCs performance as population stratification adjustment covariates, no correlation was found between P values obtained from uncorrected and genome-wide corrected association analyses (r2 = 0.141), highlighting that population stratification correction is compulsory for association analyses in admixed populations. In contrast, high correlations were found when adjusting for both PC1 and PC2 for either subset of AIMs (r2 > 0.900). After multiple validations, including an independent sample, we selected a minimal panel of 32 AIMs, which are highly informative of the major ancestral components of Mexican mestizos, namely European and Native American ancestries. Finally, the correlation between the global ancestry proportions calculated using genome-wide data and our panel of 32 AIMs was r2 = 0.972. CONCLUSIONS: Our panel of 32 AIMs accurately estimated global ancestry and corrected for population stratification in association studies in Mexican individuals.

Population data for 21 autosomal STR loci (GlobalFiler kit) in two Mexican-Mestizo population from the northwest, Mexico.

Mexican Mestizos (admixed) have been poorly studied for short tandem repeats (STRs) included for new human identification (HID) kits, such as the GlobalFiler PCR Amplification kit. Therefore, this kit was analyzed in 784 unrelated volunteers from the city of Tijuana (n = 381) and Sonora state (n = 403) in the northwest region of Mexico. Allele frequencies, forensic parameters, Hardy-Weinberg equilibrium, and linkage equilibrium were estimated or evaluated for 21 autosomal STRs, respectively. For this HID kit, the combined power of discrimination (PD) was > 0.99999999999999 (RMP range = 1.23 to 3.0 × 10-25), and the combined power of exclusion (PE) were 0.999999993 and 0.999999997 in Tijuana city and Sonora state, respectively. Interpopulation analyses based on STRs of the GlobalFiler kit was performed, including four Mexican Native American, one Mexican Mestizo, and four ethnic American populations (USA), previously studied. The low-but significant-differentiation observed among Mexican Mestizos (FST = 0.0969%; p = 0.02584) justifies the creation of STR databases for HID purposes in this country. In brief, results allow the confident use of the GlobalFiler kit for HID purposes in Mestizo population from the Northwest region Mexico.

Patrones de frecuencias en 100 marcadores informativos de ancestría entre dos etnias indígenas y dos poblaciones mestizas de Colombia / Frequency pattern analysis of 100 ancestry informative markers between two ethnics groups and two populations of Colombia

Colombia es el segundo país con mayor cantidad de etnias Amerindias del continente gracias a su ubicación geográfica y a que se encuentra en el Noroccidente del continente Sur Americano tuvo que haber sido un corredor para las migraciones de los Amerindios. Pero debido a la mezcla amerindia, europea y africana, ocurrida en diferentes proporciones a lo largo del país hubo cambios en las dinámicas poblacionales. Ojetivo: se caracterizó molecularmente una muestra indígena proveniente de dos etnias ­ Pijao y Nasa Paez, - y otra muestra de individuos mestizos no relacionados del Tolima; con el fin de identificar heterocigocidad, frecuencias alélicas y distancias Fst, mediante el análisis de 100 marcadores informativos de ancestría (SNPs autosómicos). Metodología: Para la realización de este estudio se obtuvo ADN a partir de muestras de sangre tomadas en personas indígenas y mestizas de las regiones ya mencionadas, para tipificar 100 SNPs autosómicos o Marcadores de informativos de Ancestría (AIMs). Resultados: los análisis de la Heterocigocidad (Het) mostraron que los valores bajos se presentaban en las etnias indígenas Nasa (0,181) y Pijaos (0,250), mientras que los de Planadas (0,402) e Ibagué (0,415) presentaron los valores altos. Los análisis realizados de manera global mostraron que las poblaciones del Tolima son menos heterocigotas que las poblaciones ancestrales. Conclusiones: La población nativa Nasa, es la de mayor conservación de la variación nativa ancestral reflejada con los análisis de heterocigocidad y posee una mayor distancia genética con respecto a las poblaciones mestizas.

Colombia is the second country with the largest number of amerindian ethnic groups on the continent thanks to its geographical location and that it is located in the Northwest of the South American continent, it had to have been a corridor for the Amerindian migrations. But due to the Amerindian, European and African mix, which occurred in different proportions throughout the country, there were changes in population dynamics. Objective: an indigenous sample from two ethnic groups - Pijao and Nasa Paez, was molecularly characterized - and another sample of unrelated mestizo individuals from Tolima; to identify heterozygosity, allelic frequencies and Fst distances, by analyzing 100 informative markers of ancestry (autosomal SNPs). Methodology: To carry out this study, DNA was obtained from blood samples taken in indigenous and mestizo people from the aforementioned regions, to typify 100 autosomal SNPs or ancestry informative markers (AIMs). Results: Heterozygous (Het) analyzes showed that low values were presented in the Nasa (0,181) and Pijaos (0,250) indigenous ethnic groups, while those of Planadas (0,402) and Ibagué (0,415) presented high values. Analyzes performed globally showed that Tolima populations are less heterozygous than ancestral populations. Conclusions: The Nasa native population is the one with the greatest conservation of the ancestral native variation reflected with the heterozygous analyzes and has a greater genetic distance concerning the mestizo populations.

Allele diversity of the killer cell immunoglobulin-like receptors KIR3DL1/S1 and the combination with their HLA ligands in Mexican Mestizos from Mexico City.

Killer cell immunoglobulin-like receptors (KIRs), expressed on Natural Killer (NK) cells, activate/inhibit NK cell function through interactions with their HLA-A, B and C ligands. KIR3DL1 is one of the most polymorphic genes and its effect varies depending on the interaction of the specific allotype with its Bw4 ligand. We investigated the allelic diversity of KIR3DL1/S1 using sequence based typing and we typed as well, their Bw4 ligands in Mexican Mestizos of Mexico City. The results showed that this population has a great KIR3DL1 allelic diversity with ∗01502 (19.9%), ∗00101 (13.2%) and ∗00501 (12.8%) being the most common alleles, while KIR3DS1 showed predominance of ∗01301 (86%); these data agree with the diversity found in most populations studied. At least one KIR3DL1-HIGH surface expression allele was present in 67.5% of the subjects. Phylogenetic comparisons between Mestizos and 28 different populations showed that allelic diversity of KIR3DL1/S1 was similar in Mexican Mestizos from Mexico and in Hispanics from USA. Knowledge of KIR and MHC diversity worldwide is fundamental for understanding the impact of KIR and KIR-ligand polymorphism on NK cell effector functions and is relevant in genetic anthropology, disease association and transplantation.