Genetic basis and spatial distribution of glucose-6-phosphate dehydrogenase deficiency in ecuadorian ethnic groups: a malaria perspective.

BACKGROUND: Glucose-6-phosphate dehydrogenase deficiency (G6PDd) is an X-linked disorder affecting over 400 million people worldwide. Individuals with molecular variants associated with reduced enzymatic activity are susceptible to oxidative stress in red blood cells, thereby increasing the risk of pathophysiological conditions and toxicity to anti-malarial treatments. Globally, the prevalence of G6PDd varies among populations. Accordingly, this study aims to characterize G6PDd distribution within the Ecuadorian population and to describe the spatial distribution of reported malaria cases. METHODS: Molecular variants associated with G6PDd were genotyped in 581 individuals from Afro-Ecuadorian, Indigenous, Mestizo, and Montubio ethnic groups. Additionally, spatial analysis was conducted to identify significant malaria clusters with high incidence rates across Ecuador, using data collected from 2010 to 2021. RESULTS: The A- c.202G > A and A- c.968T > C variants underpin the genetic basis of G6PDd in the studied population. The overall prevalence of G6PDd was 4.6% in the entire population. However, this frequency increased to 19.2% among Afro-Ecuadorian people. Spatial analysis revealed 12 malaria clusters, primarily located in the north of the country and its Amazon region, with relative risks of infection of 2.02 to 87.88. CONCLUSIONS: The findings of this study hold significant implications for public health interventions, treatment strategies, and targeted efforts to mitigate the burden of malaria in Ecuador. The high prevalence of G6PDd among Afro-Ecuadorian groups in the northern endemic areas necessitates the development of comprehensive malaria eradication strategies tailored to this geographical region.

A comparative analysis of lung function and spirometry parameters in genotype-controlled natives living at low and high altitude.

BACKGROUND: The reference values for lung function are associated to anatomical and lung morphology parameters, but anthropometry it is not the only influencing factor: altitude and genetics are two important agents affecting respiratory physiology. Altitude and its influence on respiratory function has been studied independently of genetics, considering early and long-term acclimatization. OBJECTIVE: The objective of this study is to evaluate lung function through a spirometry study in autochthonous Kichwas permanently living at low and high-altitude. METHODOLOGY: A cross-sectional study of spirometry differences between genetically matched lowland Kichwas from Limoncocha (230 m) at Amazonian basin and high-altitude Kichwas from Oyacachi (3180 m) in Andean highlands. The sample size estimates permitted to recruited 118 patients (40 men and 78 women) from Limoncocha and 95 (39 men and 56 women) from Oyacachi. Chi-square method was used to analyze association or independence of categorical variables, while Student's t test was applied to comparison of means within quantitative variables. ANOVA, or in the case that the variables didn't meet the criteria of normality, Kruskal Wallis test were used to compare more than two groups. RESULTS: The FVC and the FEV1 were significantly greater among highlanders than lowlanders (p value < 0.001), with a proportion difference of 15.2% for men and 8.5% for women. The FEV1/FVC was significantly higher among lowlanders than highlanders for men and women. A restrictive pattern was found in 12.9% of the participants. CONCLUSION: Residents of Oyacachi had greater FVC and FEV1 than their peers from Limoncocha, a finding physiologically plausible according to published literature. Lung size and greater ventilatory capacities could be an adaptive mechanism developed by the highlander in response to hypoxia. Our results support the fact that this difference in FVC and FEV1 is a compensatory mechanism towards lower barometric and alveolar partial pressure of oxygen pressure.

Investigating genetic diversity in admixed populations from Ecuador.

OBJECTIVES: According to demographic history, Ecuador has experienced shifts in its Native American populations caused by European colonization and the African slave trade. The continuous admixture events among Europeans, Native Americans, and Africans occurred differently in each region of the country, producing a stratified population. Thus, the aim of this study was to investigate the level of genetic substructure in the Ecuadorian Mestizo population. MATERIALS AND METHODS: A total of 377 male and 209 female samples were genotyped for two sets of X-chromosomal markers (32 X-Indels and 12 X-STRs). Population analyses performed included Hardy-Weinberg equilibrium tests, LD analysis, PCA, pairwise FST s, and AMOVA. RESULTS: Significant levels of LD were observed between markers separated by distances of less than 1 cM, as well as between markers separated by distances varying from 10.891 to 163.53 cM. Among Ecuadorian regions, Amazonia showed the highest average R2 value. DISCUSSION: When X-chromosomal and autosomal differentiation values were compared, a sex-biased admixture between European men and Native American and African women was revealed, as well as between African men and Native American women. Moreover, a distinct Native American ancestry was discernible in the Amazonian population, in addition to sex-biased gene flow between Amazonia and the Andes and Pacific coast regions. Overall, these results underline the importance of integrating X chromosome information to achieve a more comprehensive view of the genetic and demographic histories of South American admixed populations.

A report of congenital adrenal hyperplasia due to 17α-hydroxylase deficiency in two 46,XX sisters.

Congenital adrenal hyperplasia (CAH) is a group of rare orphan disorders caused by mutations in seven different enzymes that impair cortisol biosynthesis. The 17α-hydroxylase deficiency (17OHD) is one of the less common forms of CAH, corresponding to approximately 1% of the cases, with an estimated annual incidence of 1 in 50,000 newborns. Cases description - two phenotypically female Ecuadorian sisters, both with primary amenorrhea, absence of secondary sexual characteristics, and osteoporosis. High blood pressure was present in the older sister. Hypergonadotropic hypogonadism profile was observed: decreased cortisol and dehydroepiandrosterone sulfate (DHEAS), increased adrenocorticotropic hormone (ACTH) and normal levels of 17-hydroxyprogesterone, extremely high deoxycorticosterone (DOC) levels, and a tomography showed bilateral adrenal hyperplasia in both sisters. Consanguinity was evident in their ancestors. Furthermore, in the exon 7, the variant c.1216T > C, p.Trp406Arg was detected in homozygosis in the CYP17A1 gene of both sisters. We report a homozygous missense mutation in the CYP17A1 gene causing 17OHD in two sisters from Loja, Ecuador. According to the authors, this is the first time such deficiency and mutation are described in two members of the same family in Ecuador.

A study of the molecular variants associated with lactase persistence in different Ecuadorian ethnic groups.

OBJECTIVE: Lactase persistence (LP) is an adaptive trait that certain human populations have acquired in response to lactose consumption in adulthood. The T-13910 variant has been reported as a causal polymorphism in Europeans. The Ecuadorian population has been described as multicultural and multiethnic, comprised of three main ethnic groups (Mestizo, Native Amerindian, and Afro-Ecuadorian). The aim of the study was to identify the molecular basis of LP in these admixed populations for the first time and determine the association between the T-13910 marker and the European ancestry proportion of each ethnic group. METHODS: Genotyping was performed in 741 Ecuadorian individuals by sequencing a 576 bp region around the -13910 position upstream of the LCT gene. The ancestry proportions of Mestizo, Afro-Ecuadorian, and Native Amerindians were calculated using Ancestry Informative Markers and were compared with the diversity panel of the Human Genome Diversity Project. RESULTS: LP prevalence calculated from T-13910 allele frequency in Mestizo, Afro-Ecuadorian, and Native Amerindians was 24.4%, 16%, and 12.5%, respectively. The ancestry percentage correlated to the admixture proportion of each ethnic group, and the C/T-13910 genotype frequency was influenced by the European ancestry proportion. CONCLUSIONS: The presence of the T-13910 polymorphism in the Ecuadorian population suggested that LP was a trait introduced by European migration and inherited by admixture that occurred during the colonization of South America. This variant was not fixed in a population with a history of admixture, and its allele frequency was proportional to the ancestry proportion of each Ecuadorian ethnic group. Am. J. Hum. Biol. 28:774-781, 2016. © 2016Wiley Periodicals, Inc.

Comparison of the genetic background of different Colombian populations using the SNPforID 52plex identification panel.

Various strategies for analysing SNP markers and genotyping have been published with the goal of obtaining informative profiles from biological samples that contain only small amounts of template and/or degraded DNA. In this study, a multiplex assay of 52 autosomal single-nucleotide polymorphisms (SNPs) was used to analyse 438 individuals from urban populations from different regions of Colombia, as well as a sample of 50 Native American individuals of the Pastos ethnic group from Nariño. To determine if significant differences in these 52 SNPs exist between the distinct regions of Colombia, genetic distance and admixture analyses were performed based on the available data for 17 different Colombian population groups and for population groups from Africa, Europe and America. The results demonstrate significant differences between the populations from the Southwest Andean, Central-West Andean, Central-East Andean, Orinoquian and northern Colombian Pacific Coast regions. Most of the regions exhibited a European and Native American admixture. One exception is the population from the region of Chocó (on the northern Pacific Coast), which exhibits a high proportion of African admixture (54 %). From the observed genetic backgrounds, it is possible to conclude that a single reference database for the entire country would not be suitable for forensic purposes. The allele frequencies and the forensically relevant parameters were calculated for all of the markers in each Colombian region with significant values for the combined matching probability (power of discrimination ≥0.99999999999999990) and the combined probability of exclusion (≥0.9990) in trios that were obtained from all of the population groups.

Microsatellites' mutation modeling through the analysis of the Y-chromosomal transmission: Results of a GHEP-ISFG collaborative study.

The Spanish and Portuguese Speaking Working Group of the International Society for Forensic Genetics (GHEP-ISFG) organized a collaborative study on mutations of Y-chromosomal short tandem repeats (Y-STRs). New data from 2225 father-son duos and data from 44 previously published reports, corresponding to 25,729 duos, were collected and analyzed. Marker-specific mutation rates were estimated for 33 Y-STRs. Although highly dependent on the analyzed marker, mutations compatible with the gain or loss of a single repeat were 23.2 times more likely than those involving a greater number of repeats. Longer alleles (relatively to the modal one) showed to be nearly twice more mutable than the shorter ones. Within the subset of longer alleles, the loss of repeats showed to be nearly twice more likely than the gain. Conversely, shorter alleles showed a symmetrical trend, with repeat gains being twofold more frequent than reductions. A positive correlation between the paternal age and the mutation rate was observed, strengthening previous findings. The results of a machine learning approach, via logistic regression analyses, allowed the establishment of algebraic formulas for estimating the probability of mutation depending on paternal age and allele length for DYS389I, DYS393 and DYS627. Algebraic formulas could also be established considering only the allele length as predictor for DYS19, DYS389I, DYS389II-I, DYS390, DYS391, DYS393, DYS437, DYS439, DYS449, DYS456, DYS458, DYS460, DYS481, DYS518, DYS533, DYS576, DYS626 and DYS627 loci. For the remaining Y-STRs, a lack of statistical significance was observed, probably as a consequence of the small effective size of the subsets available, a common difficulty in the modeling of rare events as is the case of mutations. The amount of data used in the different analyses varied widely, depending on how the data were reported in the publications analyzed. This shows a regrettable waste of produced data, due to inadequate communication of the results, supporting an urgent need of publication guidelines for mutation studies.

A tool for the cheap and rapid screening of SARS-CoV-2 variants of concern (VoCs) by Sanger sequencing.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus that, since March 2020, has been responsible for a global and ongoing pandemic. Its rapid spread over the past nearly 3 years has caused novel variants to arise. To monitor the circulation and emergence of SARS-CoV-2 variants, surveillance systems based on nucleotide mutations are required. In this regard, we searched in the spike, ORF8, and nucleocapsid genes to detect variable sites among SARS-CoV-2 variants. We describe polymorphic genetic regions that enable us to differentiate between the Alpha, Beta, Gamma, Delta, and Omicron variants of concern (VoCs). We found 21 relevant mutations, 13 of which are unique for Omicron lineages BA.1/BA.1.1, BA.2, BA.3, BA.4, and BA.5. This genetic profile enables the discrimination between VoCs using only four reverse transcription PCR fragments and Sanger sequencing, offering a cheaper and faster alternative to whole-genome sequencing for SARS-CoV-2 surveillance. IMPORTANCE Our work describes a new (Sanger sequencing-based) screening methodology for SARS-CoV-2, performing PCR amplifications of a few target regions to detect diagnostic mutations between virus variants. Using the methodology developed in this work, we were able to discriminate between the following VoCs: Alpha, Beta, Gamma, Delta, and Omicron (BA.1/BA.1.1, BA.2, BA.3, BA.4, and BA.5). This becomes important, especially in low-income countries where current methodologies like next-generation sequencing have prohibitive costs. Furthermore, rapid detection would allow sanitary authorities to take rapid measures to limit the spread of the virus and therefore reduce the probability of new virus dispersion. With this methodological approach, 13 previously unreported diagnostic mutations among several Omicron lineages were found.

Population-Specific Distribution of TPMT Deficiency Variants and Ancestry Proportions in Ecuadorian Ethnic Groups: Towards Personalized Medicine.

Purpose: Thiopurine S-methyltransferase (TPMT) is an enzyme that metabolizes purine analogs, agents used in the treatment of acute lymphoblastic leukemia. Improper drug metabolism leads to toxicity in chemotherapy patients and reduces treatment effectiveness. TPMT variants associated with reduced enzymatic activity vary across populations. Therefore, studying these variants in heterogeneous populations, such as Ecuadorians, can help identify molecular causes of deficiency for this enzyme. Methods: We sequenced the entire TPMT coding region in 550 Ecuadorian individuals from Afro-Ecuadorian, Indigenous, Mestizo, and Montubio ethnicities. Moreover, we conducted an ancestry analysis using 46 informative ancestry markers. Results: We identified 8 single nucleotide variants in the coding region of TPMT. The most prevalent alleles were TPMT*3A, TPMT*3B, and TPMT*3C, with frequencies of 0.055, 0.012, and 0.015, respectively. Additionally, we found rare alleles TPMT*4 and TPMT*8 with frequencies of 0.005 and 0.003. Correlating the ancestry proportions with TPMT-deficient genotypes, we observed that the Native American ancestry proportion influenced the distribution of the TPMT*1/TPMT*3A genotype (OR = 5.977, p = 0.002), while the contribution of African ancestral populations was associated with the TPMT*1/TPMT*3C genotype (OR = 9.769, p = 0.003). The rates of TPMT-deficient genotypes observed in Mestizo (f = 0.121) and Indigenous (f = 0.273) groups provide evidence for the influence of Native American ancestry and the prevalence of the TPMT*3A allele. In contrast, although Afro-Ecuadorian groups demonstrate similar deficiency rates (f = 0.160), the genetic factors involved are associated with contributions from African ancestral populations, specifically the prevalent TPMT*3C allele. Conclusion: The distribution of TPMT-deficient variants offers valuable insights into the populations under study, underscoring the necessity for genetic screening strategies to prevent thiopurine toxicity events among Latin American minority groups.

Genetic Variations of the DPYD Gene and Its Relationship with Ancestry Proportions in Different Ecuadorian Trihybrid Populations.

Dihydropyrimidine dehydrogenase is one of the main pharmacological metabolizers of fluoropyrimidines, a group of drugs widely used in clinical oncology. Around 20 to 30% of patients treated with fluoropyrimidines experience severe toxicity caused by a partial or total decrease in enzymatic activity. This decrease is due to molecular variants in the DPYD gene. Their prevalence and allelic frequencies vary considerably worldwide, so their description in heterogeneous groups such as the Ecuadorian population will allow for the description of pharmacogenetic variants and proper characterization of this population. Thus, we genotyped all the molecular variants with a predictive value for DPYD in a total of 410 Ecuadorian individuals belonging to Mestizo, Afro-Ecuadorian, and Indigenous ethnic groups. Moreover, we developed a genetic ancestry analysis using 46 autosomal ancestry informative markers. We determined 20 genetic variations in 5 amplified regions, including 3 novel single nucleotide variants. The allele frequencies for DPYD variants c.1627G>A (*5, rs1801159), c.1129-15T>C (rs56293913), c.1218G>A (rs61622928), rs1337752, rs141050810, rs2786783, rs2811178, and g.97450142G>A (chr1, GRCh38.p13) are significantly related to Native American and African ancestry proportions. In addition, the FST calculated from these variants demonstrates the closeness between Indigenous and Mestizo populations, and evidences genetic divergence between Afro-Ecuadorian groups when compared with Mestizo and Indigenous ethnic groups. In conclusion, the genetic variability in the DPYD gene is related to the genetic component of ancestral populations in different Ecuadorian ethnic groups. The absence and low frequency of variants with predictive value for fluoropyrimidine toxicity such as DPYD *2A, HapB3, and c.2846A>T (prevalent in populations with European ancestry) is consistent with the genetic background found.

Testing the Ion AmpliSeq™ HID Y-SNP Research Panel v1 for performance and resolution in admixed South Americans of haplogroup Q.

Y haplogroups, defined by Y-SNPs, allow the reconstruction of the human Y chromosome genealogy, which is important for population, evolutionary and forensic genetics. In this study, Y-SNPs were typed and haplogroups inferred with the MPS Ion AmpliSeq™ HID Y-SNP Research Panel v1, as a high-throughput approach. Firstly, the performance of the panel was evaluated with different DNA input amounts, reagent volumes and cycle numbers. DNA-inputs from 0.5 to 1 ng generated the most balanced read depth. Combined with full reagent and 19 cycles, this offered the highest number of amplicons with a sequencing read depth of at least 20 reads. Secondly, the sub-haplogroups of 182 admixed South Americans and Greenlanders belonging to haplogroup Q were inferred and tested for potential improvement in resolution. Most samples were assigned to lineage Q-M3 with some samples assigned to lineages upstream (Q-M346, L56, L57; Q-L331, L53; Q-L54; Q-CTS11969, CTS11970) or parallel (Q-L330, L334; Q-Z780/M971) to Q-M3. Only one sample was assigned to a downstream lineage (Q-Z35615, Z35616). Most individuals of haplogroup Q with NAM ancestry could neither be distinguished from each other, nor from half of the Greenlandic samples. Typing additional, known SNPs within lineage Q-M3, Z19483 and SA05, increased the resolution of predicted haplogroups. The search for novel variants in the sequenced regions allowed the detection of 42 variants and the subdivision of lineage Q-M3 into new subclades. The variants found in six of these subclades were exclusive to certain South American countries. In light of the limited differentiation of haplogroup Q samples, the additional information on known or novel SNPs disclosed in this study when using MPS Ion AmpliSeq™ HID Y-SNP Research Panel v1 should be included in the Yleaf software, to increase the differentiation of lineage Q-M3.

INFECTION DYNAMICS OF BATRACHOCHYTRIUM DENDROBATIDIS IN TWO FROG SPECIES INHABITING QUITO'S METROPOLITAN GUANGÜILTAGUA PARK, ECUADOR.

Batrachochytrium dendrobatidis (Bd) infection is one of the principal causes of amphibian declines worldwide. The presence of Bd has been determined in Gastrotheca riobambae tadpoles that inhabit ponds in Quito's Metropolitan Guangüiltagua Park, Ecuador. This study sought to determine whether these tadpoles are infected and to determine the presence of chytridiomycosis in another frog species, Pristimantis unistrigatus, which also inhabits the park and has different reproductive biology and distinct behavioral habits. We used end-point and real-time PCR techniques to detect and quantify Bd infection. At 1 yr, samples were taken from the skin of P. unistrigatus using swabs and were also taken from the mouthparts of G. riobambae tadpoles. It was found that the two species were infected with a Bd prevalence of 39% (53/135) in G. riobambae tadpoles and 15% (57/382) in P. unistrigatus frogs. The two types of samples (tissue and swabs) from mouthparts showed differences in the zoospores per microliter loads (x̄=1,376.7±3,450.2 vs. x̄=285.0±652.3). Moreover, a correlation (r2=0.621) was discovered between the monthly mean maximum temperature of the pond with disease prevalence in G. riobambae tadpoles. Infection levels in the P. unistrigatus population varied significantly over time, and distance to the pond was a determinant factor for infection intensity.

Hematological Parameters, Lipid Profile, and Cardiovascular Risk Analysis Among Genotype-Controlled Indigenous Kiwcha Men and Women Living at Low and High Altitudes.

Introduction: Human adaptation to high altitude is due to characteristic adjustments at every physiological level. Differences in lipid profile and cardiovascular risk factors in altitude dwellers have been previously explored. Nevertheless, there are no reports available on genotype-controlled matches among different altitude-adapted indigenous populations. Objective: To explore the possible differences in plasma lipid profile and cardiovascular risk among autochthonous Kiwcha people inhabitants of low and high-altitude locations. Methodology: A cross-sectional analysis of plasmatic lipid profiles and cardiovascular risk factors in lowland Kiwchas from Limoncocha (230 m) and high-altitude Kiwchas from Oyacachi (3,800 m). Results: In the low altitude group, 66% were women (n = 78) and 34% (n = 40) were men, whereas in the high altitude group, 59% (n = 56) were women and 41% (n = 41%) were men. We found the proportion of overweight and obese individuals to be higher among low altitude dwellers (p < 0.05). Red blood cells (RBCs), hemoglobin concentration, and SpO2% were higher among high altitude dwellers and the erythrocyte size was found to be smaller at high altitude. The group located at low altitude also showed lower levels of plasma cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL), but most of these differences are not influenced by gender or elevation. Conclusions: Living at an altitude elicits well-known adaptive physiological changes such as erythrocyte count, hemoglobin concentration, hematocrit level, and serum glucose level. We also report clinical differences in the plasma lipid profile, with higher levels of cholesterol, HDL, and LDL in inhabitants of the Andes Mountain vs. their Amazonian basin peers. Despite this, we did not find significant differences in cardiovascular risk.

Paternal and maternal mutations in X-STRs: A GHEP-ISFG collaborative study.

The GHEP-ISFG organized a collaborative study to estimate mutation rates for the markers included in the Investigator Argus X-12 QS kit Qiagen. A total of 16 laboratories gathered data from 1,612 father/mother/daughter trios, which were used to estimate both maternal and paternal mutation rates, when pooled together with other already published data. Data on fathers and mothers' age at the time of birth of the daughter were also available for ∼93 % of the cases. Population analyses were computed considering the genetic information of a subset of 1,327 unrelated daughters, corresponding to 2,654 haplotypes from residents in several regions of five countries: Argentina, Brazil, Ecuador, Portugal and Spain. Genetic differentiation analyses between the population samples from the same country did not reveal signs of significant stratification, although results from Hardy-Weinberg and linkage disequilibrium tests indicated the need of larger studies for Ecuador and Brazilian populations. The high genetic diversity of the markers resulted in a large number of haplotype combinations, showing the need of huge databases for reliable estimates of their frequencies. It should also be noted the high number of new alleles found, many of them not included in the allelic ladders provided with the kit, as very diverse populations were analyzed. The overall estimates for locus specific average mutation rates varied between 7.5E-04 (for DXS7423) and 1.1E-02 (for DXS10135), the latter being a troublesome figure for kinship analyses. Most of the found mutations (∼92 %) are compatible with the gain or loss of a single repeat. Paternal mutation rates showed to be 5.2 times higher than maternal ones. We also found that older fathers were more prone to transmit mutated alleles, having this trend not been observed in the case of the mothers.

Consensus strategy in genes prioritization and combined bioinformatics analysis for preeclampsia pathogenesis.

BACKGROUND: Preeclampsia is a multifactorial disease with unknown pathogenesis. Even when recent studies explored this disease using several bioinformatics tools, the main objective was not directed to pathogenesis. Additionally, consensus prioritization was proved to be highly efficient in the recognition of genes-disease association. However, not information is available about the consensus ability to early recognize genes directly involved in pathogenesis. Therefore our aim in this study is to apply several theoretical approaches to explore preeclampsia; specifically those genes directly involved in the pathogenesis. METHODS: We firstly evaluated the consensus between 12 prioritization strategies to early recognize pathogenic genes related to preeclampsia. A communality analysis in the protein-protein interaction network of previously selected genes was done including further enrichment analysis. The enrichment analysis includes metabolic pathways as well as gene ontology. Microarray data was also collected and used in order to confirm our results or as a strategy to weight the previously enriched pathways. RESULTS: The consensus prioritized gene list was rationally filtered to 476 genes using several criteria. The communality analysis showed an enrichment of communities connected with VEGF-signaling pathway. This pathway is also enriched considering the microarray data. Our result point to VEGF, FLT1 and KDR as relevant pathogenic genes, as well as those connected with NO metabolism. CONCLUSION: Our results revealed that consensus strategy improve the detection and initial enrichment of pathogenic genes, at least in preeclampsia condition. Moreover the combination of the first percent of the prioritized genes with protein-protein interaction network followed by communality analysis reduces the gene space. This approach actually identifies well known genes related with pathogenesis. However, genes like HSP90, PAK2, CD247 and others included in the first 1% of the prioritized list need to be further explored in preeclampsia pathogenesis through experimental approaches.

Evaluating the X chromosome-specific diversity of Colombian populations using insertion/deletion polymorphisms.

The European and African contribution to the pre-existing Native American background has influenced the complex genetic pool of Colombia. Because colonisation was not homogeneous in this country, current populations are, therefore, expected to have different proportions of Native American, European and African ancestral contributions. The aim of this work was to examine 11 urban admixed populations and a Native American group, called Pastos, for 32 X chromosome indel markers to expand the current knowledge concerning the genetic background of Colombia. The results revealed a highly diverse genetic background comprising all admixed populations, harbouring important X chromosome contributions from all continental source populations. In addition, Colombia is genetically sub-structured, with different proportions of European and African influxes depending on the regions. The samples from the North Pacific and Caribbean coasts have a high African ancestry, showing the highest levels of diversity. The sample from the South Andean region showed the lowest diversity and significantly higher proportion of Native American ancestry than the other samples from the North Pacific and Caribbean coasts, Central-West and Central-East Andean regions, and the Orinoquian region. The results of admixture analysis using X-chromosomal markers suggest that the high proportion of African ancestry in the North Pacific coast was primarily male driven. These men have joined to females with higher Native American and European ancestry (likely resulting from a classic colonial asymmetric mating type: European male x Amerindian female). This high proportion of male-mediated African contributions is atypical of colonial settings, suggesting that the admixture occurred during a period when African people were no longer enslaved. In the remaining regions, the African contribution was primarily female-mediated, whereas the European counterpart was primarily male driven and the Native American ancestry contribution was not gender biased.