Insights into the Y chromosome human diversity in Uruguay.

BACKGROUND: With regard to the origin of its population and microevolutionary processes, Uruguay exhibits distinctive features that distinguish it from other countries in Latin America, while at the same time sharing several similarities. In this article, we will focus on the variability of paternal genetic lineages in two geographical regions with different histories that can be considered as examples of distinct populations for the continent. In general terms, the genetic diversity is a result of different demographic processes related to the American conquest and colonisation. These resulted in distinct ancestral components which vary geographical and depend on the distribution by sex within these components. In Uruguay, native maternal haplogroups are significantly more frequent in the North. Although there are several studies about the geneticvariability of Uruguay, little is known about male genetic lineages. AIMS: The aim of this work is to present an updated study of the male genetic variability of the Uruguayan population. METHODS: We analyzed 13 biallelic markers and 27 STRs located in the male-specific region of the Y chromosome for 157 males: 98 from the capital, Montevideo, and 59 from Tacuarembó. RESULTS: Almost all haplogroups found in both locations are European (99% and 93.2% respectively). One Sub-Saharan African haplogroup was found in Montevideo (1%) and 2 in Tacuarembó (3%), while Native haplogroups were found only in Tacuarembó, evidencing a strong sex-biased admixture. By crossing genetic and genealogical information we could relate European haplogroups with different waves and times of migrations. DISCUSSION: Network analysis indicated a very diverse male population, suggesting that European migrants came from heterogeneous geographic locations and in different waves. Tacuarembó has closer population affinities with Iberian populations while Montevideo is more diverse. Male population expansion expansion, can be explained by the large number of migrants that arrived during the XIX century and the first half of the XX century. CONCLUSIONS: The Uruguayan male gene pool is the result of several migration waves with diverse origins, with strong sex-biased admixture that can be explained by the European migration, the violence against the indigenous males, and the segregation of the Africansadmixture that can be explained due to European migration, violence against Natives, and segregation against African males.admixture that can be explained due to European migration, violence against Natives, and segregation against African males.admixture that can be explained due to European migration, violence against Natives, and segregation against African males.admixture that can be explained due to European migration, violence against Natives, and segregation of hte Africans.

Oxytocin system polymorphisms rs237887 and rs2740210 variants increase the risk of depression in pregnant women with early abuse.

Prepartum depression is associated with early adversity, pregnancy complications, preterm delivery, postpartum depression, and long-term effects on child neurodevelopment. The oxytocin (OXT) system is affected by early adverse experiences and has been associated with depression. In the current study, we investigated risk factors for prenatal depressive symptoms, mainly the effects of early childhood and adolescence trauma, in combination with the presence of certain variants of polymorphisms of OXT and OXT receptor (OXTR) genes. We hypothesized that early childhood and adolescence trauma has higher negative effects in carriers of genetic variants of the OXT/OXTR system, increasing their risk for depression. Early in pregnancy (8-14 weeks), 141 pregnant women from a Uruguayan population were asked to provide DNA samples and complete questionnaires that assessed their experience of child abuse, depression symptoms, and other variables that included demographic information. Our results showed that 23.5% of pregnant women had depressive symptoms. Several OXT and OXTR genetic variants were associated with higher risk of prepartum depression only in those pregnant women who suffered emotional abuse during infancy or adolescence. Logistic regression (Nagelkerke's R2  = .33) revealed that women who suffered early abuse and were carriers of the variants CC of rs2740210 (OXT) or AA of rs237887 (OXTR) had significantly higher risk of experiencing depressive symptoms. Antecedents of psychiatric disorders also contributed to the risk of depression. We conclude that emotional abuse contributes to the risk of depression in different ways in women carrying different OXT and OXTR genetic variants. Early detection and closer follow-up of women with child abuse and certain OXT genetic variants, among other risk factors, could reduce the long-term impact of prepartum depression.

Investigating DNA methylation as a potential mediator between pigmentation genes, pigmentary traits and skin cancer.

Pigmentation characteristics are well-known risk factors for skin cancer. Polymorphisms in pigmentation genes have been associated with these traits and with the risk of malignancy. However, the functional relationship between genetic variation and disease is still unclear. This study aims to assess whether pigmentation SNPs are associated with pigmentary traits and skin cancer via DNA methylation (DNAm). Using a meta-GWAS of whole-blood DNAm from 36 European cohorts (N = 27,750; the Genetics of DNA Methylation Consortium, GoDMC), we found that 19 out of 27 SNPs in 10 pigmentation genes were associated with 391 DNAm sites across 30 genomic regions. We examined the effect of 25 selected DNAm sites on pigmentation traits, sun exposure phenotypes and skin cancer and on gene expression in whole blood. We uncovered an association of DNAm site cg07402062 with red hair in the Avon Longitudinal Study of Parents and Children (ALSPAC). We also found that the expression of ASIP and CDK10 was associated with hair colour, melanoma and basal cell carcinoma. Our results indicate that DNAm and expression of pigmentation genes may play a role as potential mediators of the relationship between genetic variants, pigmentation phenotypes and skin cancer and thus deserve further scrutiny.

Discovery of novel DNA methylation biomarkers for non-invasive sporadic breast cancer detection in the Latino population.

Human diversity is one of the main pitfalls in the development of robust worldwide biomarkers in oncology. Epigenetic variability across human populations is associated with different genetic backgrounds, as well as variable lifestyles and environmental exposures, each of which should be investigated. To identify potential non-invasive biomarkers of sporadic breast cancer in the Uruguayan population, we studied genome-wide DNA methylation using Illumina methylation arrays in leukocytes of 22 women with sporadic breast cancer and 10 healthy women in a case-control study. We described a panel of 38 differentially methylated CpG positions that was able to cluster breast cancer patients (BCP) and controls, and that also recapitulated methylation differences in 12 primary breast tumors and their matched normal breast tissue. Moving forward, we simplified the detection method to improve its applicability in a clinical setting and used an independent well-characterized cohort of 80 leukocyte DNA samples from BCP and 80 healthy controls to validate methylation results at specific cancer-related genes. Our investigations identified methylation at CYFIP1 as a novel epigenetic biomarker candidate for sporadic breast cancer in the Uruguayan population. These results provide a proof-of-concept for the design of larger studies aimed at validating biomarker panels for the Latin American population.

Genomic Diversity in Sporadic Breast Cancer in a Latin American Population.

Among Latin American women, breast cancer incidences vary across populations. Uruguay and Argentina have the highest rates in South America, which are mainly attributed to strong, genetic European contributions. Most genetic variants associated with breast cancer were described in European populations. However, the vast majority of genetic contributors to breast cancer risk remain unknown. Here, we report the results of a candidate gene association study of sporadic breast cancer in 176 cases and 183 controls in the Uruguayan population. We analyzed 141 variants from 98 loci that have been associated with overall breast cancer risk in European populations. We found weak evidence for the association of risk variants rs294174 (ESR1), rs16886165 (MAP3K1), rs2214681 (CNTNAP2), rs4237855 (VDR), rs9594579 (RANKL), rs8183919 (PTGIS), rs2981582 (FGFR2), and rs1799950 (BRCA1) with sporadic breast cancer. These results provide useful insight into the genetic susceptibility to sporadic breast cancer in the Uruguayan population and support the use of genetic risk scores for individualized screening and prevention.

Effect of 15 BMI-Associated Polymorphisms, Reported for Europeans, across Ethnicities and Degrees of Amerindian Ancestry in Mexican Children.

In Mexico, the genetic mechanisms underlying childhood obesity are poorly known. We evaluated the effect of loci, known to be associated with childhood body mass index (BMI) in Europeans, in Mexican children from different ethnic groups. We performed linear and logistic analyses of BMI and obesity, respectively, in Mestizos and Amerindians (Seris, Yaquis and Nahuatl speakers) from Northern (n = 369) and Central Mexico (n = 8545). We used linear models to understand the effect of degree of Amerindian ancestry (AMA) and genetic risk score (GRS) on BMI z-score. Northern Mexican Mestizos showed the highest overweight-obesity prevalence (47.4%), followed by Seri (36.2%) and Central Mexican (31.5%) children. Eleven loci (SEC16B/rs543874, OLFM4/rs12429545/rs9568856, FTO/rs9939609, MC4R/rs6567160, GNPDA2/rs13130484, FAIM2/rs7132908, FAM120AOS/rs944990, LMX1B/rs3829849, ADAM23/rs13387838, HOXB5/rs9299) were associated with BMI and seven (SEC16B/rs543874, OLFM4/rs12429545/rs9568856, FTO/rs9939609, MC4R/rs6567160, GNPDA2 rs13130484, LMX1B/rs3829849) were associated with obesity in Central Mexican children. One SNP was associated with obesity in Northern Mexicans and Yaquis (SEC16B/rs543874). We found higher BMI z-score at higher GRS (ß = 0.11, p = 0.2 × 10-16) and at lower AMA (ß = -0.05, p = 6.8 × 10-7). The GRS interacts with AMA to increase BMI (ß = 0.03, p = 6.08 × 10-3). High genetic BMI susceptibility increase the risk of higher BMI, including in Amerindian children.

Ancestry and TPMT-VNTR Polymorphism: Relationship with Hematological Toxicity in Uruguayan Patients with Acute Lymphoblastic Leukemia.

6-Mercaptopurine (6-MP) is a thiopurine drug widely used in childhood acute lymphoblastic leukemia (ALL) therapy. Genes such as TPMT and NUDT15 have an outstanding role in 6-MP metabolism. Mutations in both genes explain a significant portion of hematological toxicities suffered by ALL Uruguayan pediatric patients. A variable number tandem repeat in the TPMT promoter (TPMT-VNTR) has been associated with TPMT expression. This VNTR has a conservative architecture (AnBmC). To explore new causes of hematological toxicities related to ALL therapy, we genotyped the TPMT-VNTR of 130 Uruguayan pediatric patients. Additionally, individual genetic ancestry was estimated by 45 ancestry-informative markers (AIMs). Hematological toxicity was measured as the number of leukopenia events and 6-MP dose along the maintenance phase. As previously reported, we found TPMT*2 and TPMT*3C alleles were associated to TPMT-VNTR A2BC and AB2C, respectively. However, contrasting with other reports, TPMT*3A allele was found in a heterogeneous genetic background in linkage equilibrium. Patients carrying more than 5 A repeats present a significant higher number of leukopenia events among patients without TPMT and/or NUDT15 variants. Native American ancestry and the number of A repeats were significantly correlated with the number of leukopenia events. However, the correlation between Native American ancestry and the number of leukopenia events was lost when the number of A repeats was considered as covariate. This suggests that TPMT-VNTR alleles are more relevant than Native American ancestry in the hematological toxicity. Our results emphasize that TPMT-VNTR may be used as a pharmacogenetic biomarker to predict 6-MP-related hematological toxicity in ALL childhood therapy.

Transcriptomic analysis of fetal membranes reveals pathways involved in preterm birth.

BACKGROUND: Preterm birth (PTB), defined as infant delivery before 37 weeks of completed gestation, results from the interaction of both genetic and environmental components and constitutes a complex multifactorial syndrome. Transcriptome analysis of PTB has proven challenging because of the multiple causes of PTB and the numerous maternal and fetal gestational tissues that must interact to facilitate parturition. The transcriptome of the chorioamnion membranes at the site of rupture in PTB and term fetuses may reflect the molecular pathways of preterm labor. METHODS: In this work, chorioamnion membranes from severe preterm and term fetuses were analyzed using RNA sequencing. Functional annotations and pathway analysis of differentially expressed genes were performed with the GAGE and GOSeq packages. A subset of differentially expressed genes in PTB was validated in a larger cohort using qRT-PCR and by comparing our results with genes and pathways previously reported in the literature. RESULTS: A total of 270 genes were differentially expressed (DE): 252 were upregulated and 18 were down-regulated in severe preterm births relative to term births. Inflammatory and immunological pathways were upregulated in PTB. Both types of pathways were previously suggested to lead to PTB. Pathways that were not previously reported in PTB, such as the hemopoietic pathway, appeared upregulated in preterm membranes. A group of 18 downregulated genes discriminated between term and severe preterm cases. These genes potentially characterize a severe preterm transcriptome pattern and therefore are candidate genes for understanding the syndrome. Some of the downregulated genes are involved in the nervous system, morphogenesis (WNT1, DLX5, PAPPA2) and ion channel complexes (KCNJ16, KCNB1), making them good candidates as biomarkers of PTB. CONCLUSIONS: The identification of this DE gene pattern will help with the development of a multi-gene disease classifier. These markers were generated in an admixed South American population in which PTB has a high incidence. Since the genetic background may differentially impact different populations, it is necessary to include populations such as those from South America and Africa, which are usually excluded from high-throughput approaches. These classifiers should be compared to those in other populations to obtain a global landscape of PTB.

Associations between male infertility and ancestry in South Americans: a case control study.

BACKGROUND: Infertility affects 15% of human couples, with men being responsible in approximately 50% of cases. Moreover, the aetiology of male factor infertility is poorly understood. The majority of male factor infertility remains idiopathic and potentially genetic in origin. The association of the Y chromosome and mitochondrial haplogroups with male infertility has been previously reported. This association differs between studied populations and their geographical distributions. These effects have been only rarely analysed in mixed populations, such as South Americans. METHODS: In this study, we analysed the contributions of the Y chromosome and mitochondrial haplogroups to male infertility in a mixed population. A case control study was conducted. Regular PCR and high-resolutionmelting- real-time PCR were performed to type haplogroups from fertile and infertile men. The sperm parameters from infertile men were compared in each haplogroup by logistic regression analysis and ANOVA. RESULTS: The genotyping confirmed the known admixture characteristic of the Uruguayan population. The European paternal contribution was higher than the maternal contribution in both fertile and infertile men. Neither maternal nor paternal ancestry presented differences between the cases and controls. Men belonging to the Y chromosome haplogroup F(xK) more frequently presented with an abnormal sperm morphology than men from other haplogroups. The sperm parameters were not associated with the mitochondrial haplogroups. CONCLUSIONS: The data presented in this study showed an association between male infertility and ancestry in the Uruguayan population. Specifically, abnormal sperm morphology was associated with the Y chromosome haplogroup F(xK). Since the Y chromosome lacks recombination, these data suggest that some genes that determine sperm morphology might be inherited in blocks with the region that determines specific haplogroups. However, the possible association between the Y chromosome haplogroup F(xK) and sperm morphology requires further confirmatory testing. Data linking infertility with ancestry are needed to establish the possible causes of infertility and define male populations susceptible to infertility. Whether the admixed characteristics of the Uruguayan population exert any pressure on male fertility potential must be further investigated.

Prevalence of EGFR Mutations in Lung Cancer in Uruguayan Population.

BACKGROUND: Incorporation of molecular analysis of the epidermal growth factor receptor (EGFR) gene into routine clinical practice represents a milestone for personalized therapy of the non-small-cell lung cancer (NSCLC). However, the genetic testing of EGFR mutations has not yet become a routine clinical practice in developing countries. In view of different prevalence of such mutations among different ethnicities and geographic regions, as well as the limited existing data from Latin America, our aim was to study the frequency of major types of activating mutations of the EGFR gene in NSCLC patients from Uruguay. METHODS: We examined EGFR mutations in exons 18 through 21 in 289 NSCLC Uruguayan patients by PCR-direct sequencing. RESULTS: EGFR mutations were detected in 53 of the 289 (18.3%) patients, more frequently in women (23.4%) than in men (14.5%). The distribution by exon was similar to that generally reported in the literature. CONCLUSIONS: This first epidemiological study of EGFR mutations in Uruguay reveals a wide spectrum of mutations and an overall prevalence of 18.3%. The background ethnic structure of the Uruguayan population could play an important role in explaining our findings.

Interactions between environmental factors and maternal-fetal genetic variations: strategies to elucidate risks of preterm birth.

CONTEXT: Preterm birth (PTB) is a complex disease in which medical, social, cultural, and hereditary factors contribute to the pathogenesis of this adverse event. Interactions between genes and environmental factors may complicate our understanding of the relative influence of both effects on PTB. To overcome this, we combined data obtained from a cohort of newborns and their mothers with multiplex analysis of inflammatory-related genes and several environmental risk factors of PTB to describe the environmental-genetic influence on PTB. OBJECTIVE: The study aimed to investigate the association between maternal and fetal genetic variations in genes related to the inflammation pathway with PTB and to assess the interaction between environmental factors with these variations. STUDY DESIGN: We conducted a case-control study at the Pereira Rossell Hospital Center, Montevideo, Uruguay. The study included 143 mother-offspring dyads who delivered at preterm (gestational age<37 weeks) and 108 mother-offspring dyads who delivered at term. We used real-time PCR followed by a high-resolution melting analysis to simultaneously identify gene variations involved in inflammatory pathways in the context of environmental variables. The genes analyzed were: Toll-like receptor 4 (TLR4), Interleukin 6 (IL6), Interleukin 1 beta (IL1B) and Interleukin 12 receptor beta (IL12RB). RESULTS: We detected a significant interaction between IL1B rs16944 polymorphism in maternal samples and IL6 rs1800795 polymorphism in newborns, emphasizing the role of the interaction of maternal and fetal genomes in PTB. In addition, smoke exposure and premature rupture of membranes (PROM) were significantly different between the premature group and controls. IL1B and IL6 polymorphisms in mothers were significantly associated with PTB when controlling for smoke exposure. TLR4 polymorphism and PROM were significantly associated with PTB when controlling for PROM, but only in the case of severe PTB. CONCLUSIONS: Interactions between maternal and fetal genomes may influence the timing of birth. By incorporating environmental data, we revealed genetic associations with PTB, a finding not found when we analyzed genetic data alone. Our results stress the importance of studying the effect of genotype interactions between mothers and children in the context of environmental factors because they substantially contribute to phenotype variability.

Effect of genetic ancestry on leukocyte global DNA methylation in cancer patients.

BACKGROUND: The study of genetic variants alone is not enough to explain a complex disease like cancer. Alterations in DNA methylation patterns have been associated with different types of tumor. In order to detect markers of susceptibility for the development of cutaneous melanoma and breast cancer in the Uruguayan population, we integrated genetic and epigenetic information of patients and controls. METHODS: We performed two case-control studies that included 49 individuals with sporadic cutaneous melanoma and 73 unaffected controls, and 179 women with sporadic breast cancer and 209 women controls. We determined the level of global leukocyte DNA methylation using relative quantification of 5mdC by HPLC, and we compared methylation levels between cases and controls with nonparametric statistical tests. Since the Uruguayan population is admixed and both melanoma and breast cancer have very high incidences in Uruguay compared to other populations, we examined whether individual ancestry influences global leucocyte DNA methylation status. We carried out a correlation analysis between the percentage of African, European and Native American individual ancestries, determined using 59 ancestry informative markers, and global DNA methylation in all participants. RESULTS: We detected global DNA hypomethylation in leukocytes of melanoma and breast cancer patients compared with healthy controls (p < 0.001). Additionally, we found a negative correlation between African ancestry and global DNA methylation in cancer patients (p <0.005). CONCLUSIONS: These results support the potential use of global DNA methylation as a biomarker for cancer risk. In addition, our findings suggest that the ancestral genome structure generated by the admixture process influences DNA methylation patterns, and underscore the importance of considering genetic ancestry as a modifying factor in epigenetic association studies in admixed populations such as Latino ones.

Breast cancer risk and genetic ancestry: a case-control study in Uruguay.

BACKGROUND: Uruguay exhibits one of the highest rates of breast cancer in Latin America, similar to those of developed nations, the reasons for which are not completely understood. In this study we investigated the effect that ancestral background has on breast cancer susceptibility among Uruguayan women. METHODS: We carried out a case-control study of 328 (164 cases, 164 controls) women enrolled in public hospitals and private clinics across the country. We estimated ancestral proportions using a panel of nuclear and mitochondrial ancestry informative markers (AIMs) and tested their association with breast cancer risk. RESULTS: Nuclear individual ancestry in cases was (mean ± SD) 9.8 ± 7.6% African, 13.2 ± 10.2% Native American and 77.1 ± 13.1% European, and in controls 9.1 ± 7.5% African, 14.7 ± 11.2% Native American and 76.2 ± 14.2% European. There was no evidence of a difference in nuclear or mitochondrial ancestry between cases and controls. However, European mitochondrial haplogroup H was associated with breast cancer (OR = 2.0; 95% CI 1.1, 3.5). CONCLUSIONS: We have not found evidence that overall genetic ancestry differs between breast cancer patients and controls in Uruguay but we detected an association of the disease with a European mitochondrial lineage, which warrants further investigation.

Rapid multiplex high resolution melting method to analyze inflammatory related SNPs in preterm birth.

BACKGROUND: Complex traits like cancer, diabetes, obesity or schizophrenia arise from an intricate interaction between genetic and environmental factors. Complex disorders often cluster in families without a clear-cut pattern of inheritance. Genomic wide association studies focus on the detection of tens or hundreds individual markers contributing to complex diseases. In order to test if a subset of single nucleotide polymorphisms (SNPs) from candidate genes are associated to a condition of interest in a particular individual or group of people, new techniques are needed. High-resolution melting (HRM) analysis is a new method in which polymerase chain reaction (PCR) and mutations scanning are carried out simultaneously in a closed tube, making the procedure fast, inexpensive and easy. Preterm birth (PTB) is considered a complex disease, where genetic and environmental factors interact to carry out the delivery of a newborn before 37 weeks of gestation. It is accepted that inflammation plays an important role in pregnancy and PTB. METHODS: Here, we used real time-PCR followed by HRM analysis to simultaneously identify several gene variations involved in inflammatory pathways on preterm labor. SNPs from TLR4, IL6, IL1 beta and IL12RB genes were analyzed in a case-control study. The results were confirmed either by sequencing or by PCR followed by restriction fragment length polymorphism. RESULTS: We were able to simultaneously recognize the variations of four genes with similar accuracy than other methods. In order to obtain non-overlapping melting temperatures, the key step in this strategy was primer design. Genotypic frequencies found for each SNP are in concordance with those previously described in similar populations. None of the studied SNPs were associated with PTB. CONCLUSIONS: Several gene variations related to the same inflammatory pathway were screened through a new flexible, fast and non expensive method with the purpose of analyzing their association to PTB. It can easily be used for simultaneously analyze any set of SNPs, either as the first choice for new association studies or as a complement to large-scale genotyping analysis. Given that inflammatory pathway is in the base of several diseases, it is potentially useful to analyze a broad range of disorders.

Directional mating and a rapid male population expansion in a hybrid Uruguayan population.

The Uruguayan population has been considered as mainly European descent, with a negligible Native American or African contributions. Based on serological and molecular markers, recent studies demonstrate that these two populations had an important influence in the conformation of the present one. To the Northeastern region of Uruguay, a 20% Native American contribution was estimated using autosomal markers and a 62% Native American female origin based on mitochondrial markers. In this paper, we analyze four Y chromosome markers, two biallelic loci (M3 and YAP) and two microsatellites (DYS389I and DYS391), to characterize the male genetic contribution of a sample from the Northeastern city of Tacuarembó. We take different approaches to estimate the origin of male contributions to the population of Tacuarembó; Native American contribution ranges between 1.60% and 8.31%, confirming strong directional mating, which was also detected before with mitochondrial markers. Furthermore, the male population of Tacuarembó presents the characteristic of a population that suffered a bottleneck and a posterior expansion, confirmed using two microsatellite-based statistics to analyze the past population growth; patrilocality and migration could be responsible of those characteristics.

Frequencies of the four major Amerindian mtDNA haplogroups in the population of Montevideo, Uruguay.

mtDNA Amerindian polymorphisms were studied in 108 inhabitants of Montevideo, Uruguay, using PCR RFLP analysis. Amerindian haplogroups were found in 20.4% of the sample. The frequency of Amerindian polymorphisms in Montevideo differed significantly from that observed in Tacuarembó, a city about 400 km away, indicating the high level of variation within Uruguay. Results for mitochondrial markers indicate that admixture occurred primarily as a result of Amerindian females mating with European males.

Substantial Native American female contribution to the population of Tacuarembó, Uruguay, reveals past episodes of sex-biased gene flow.

For many years it has been assumed that the population of Uruguay is almost exclusively European-derived and that the biological contribution of the native population as well as of individuals of African descent is negligible. Several recent studies based on a variety of genetic markers, mostly morphological and serological markers, have produced quite a different picture of the constitution of the Uruguayan population. The Native American contribution varies from 1-20%, while the African contribution ranges from 7-15%, in different regions of the country. In the present study we examine the way the admixture process took place in Uruguay by analyzing the ancestry of maternal lineages in a sample from the northern city of Tacuarembó. To accomplish this goal we typed mitochondrial DNA (mtDNA) markers of Native American, African, and European origin and estimated the proportions of each parental group in the admixed population. We found that 62% of all mtDNA haplogroups were of Native American descent, a surprising figure considering the "European roots" of the country. Consequently, this result assimilates Uruguay to the rest of Latin American populations where sex-biased gene flow between European men and Native American women has been the rule. We further analyzed the distribution of the four major founding mitochondrial lineages in Tacuarembó and compared it to other South American populations. We discuss our findings in the light of historical records and assess the need for additional genetic studies.

Characterization of admixture in an urban sample from Buenos Aires, Argentina, using uniparentally and biparentally inherited genetic markers.

In this study we analyzed a sample of the urban population of La Plata, Argentina, using 17 mtDNA haplogroups, the DYS 199 Y-chromosome polymorphism, and 5 autosomal population-associated alleles (PAAs). The contribution of native American maternal lineages to the population of La Plata was estimated as 45.6%, whereas the paternal contribution was much lower (10.6%), clearly indicating directional mating. Regarding autosomal evidence of admixture, the relative European, native American, and West African genetic contributions to the gene pool of La Plata were estimated to be 67.55% (+/-2.7), 25.9% (+/-4.3), and 6.5% (+/-6.4), respectively. When admixture was calculated at the individual level, we found a low correlation between the ancestral contribution estimated with uniparental lineages and autosomal markers. Most of the individuals from La Plata with a native American mtDNA haplogroup or the DYS199*T native American allele show a genetic contribution at the autosomal level that can be traced primarily to Europe. The results of this study emphasize the need to use both uniparentally and biparentally inherited genetic markers to understand the history of admixed populations.

Admixture in Hispanics: distribution of ancestral population contributions in the Continental United States.

The effect of gene flow on Hispanic populations from different geographic regions of the United States was analyzed using six autosomal DNA markers (LDLR, GYPA, HBGG, D7S8, GC, and HLA-DQA). By region of sampling, the Hispanic populations showed different ancestry contributions, from a trihybrid structure with European, Native American, and African contributions (California, Nevada, Florida, New Jersey, and Virginia) to a dihybrid structure with European and American contributions (Southwest population) or European and African contributions (Pennsylvania and Southeast population). These findings allowed us to define two regional groups, the West and the East. In the former, Native American contributions ranged from 35.58% to 57.87%; in the East region the values ranged from 0% to 21.27%. An African influence was similar in both regions, ranging from 0% to 17.11%, with a tendency of increasing in the East region. These data reflect the different origins of the Hispanic populations that led to the present ones. In the West, Hispanics are mostly of Mexican origin, and in the East, they are predominantly of Cuban and Puerto Rican origin.