Assessment of genetic ancestry and population substructure in Costa Rica by analysis of individuals with a familial history of mental disorder

The population of Costa Rica has been considered valuable for locating susceptibility genes of complex disorders because of historical events and a gradual admixture process. We present an assessment of 426 unrelated individuals with a familial history of mental disorder and with ancestors born in the Central Valley, genotyped at 730 microsatellites to evaluate genetic diversity, ancestry, and substructure at the general and regional population levels using quantitative methods. Low population substructure was found. Estimated mean ancestry proportions were 54%, 32%, and 13% for European, Amerindian, and African components, respectively, with some regional variation. The F(ST) values obtained confirm the largest genetic similarity to Europeans. Subdivision of the Amerindians into individual populations revealed strong similarity to Chibchan groups. Analysis of the African ancestry showed high similarity to West and Central African populations. Gene ancestries from other African areas were also detected, probably resulting from ancestral admixture within Africa prior to colonial times. Our analyses show, in an ethnohistorical-genetic context, that gene flow and admixture are important components of Costa Rican population history. The results confirm the need to consider the particular regional genetic structure, the effects of genetic drift and the ancestry when designing and interpreting investigations of genetic traits in this population.     

Amerindian ancestry in Argentina is associated with increased risk for systemic lupus erythematosus

Previous studies have demonstrated that in admixed populations, West African ancestry is associated with an increased prevalence of systemic lupus erythematosus (SLE). In the current study, the effect of Amerindian ancestry in SLE was examined in an admixed population in Argentina. The Argentine population is predominantly European with approximately 20% Amerindian admixture, and a very small (<2%) contribution from West Africa. The results indicate that Amerindian admixture in this population is associated with a substantial increase in SLE susceptibility risk (Odds Ratio=7.94, P=0.00006). This difference was not due to known demographic factors, including site of collection, age and gender. In addition, there were trends towards significance for Amerindian ancestry influencing renal disease, age of onset and anti-SSA antibodies. These studies suggest that populations with Amerindian admixture, like those with West African admixture, should be considered in future studies to identify additional allelic variants that predispose to SLE.     

Genetic composition of Brazilian population samples based on a set of twenty‐eight ancestry informative SNPs

Ancestry informative SNPs can be useful to estimate individual and population biogeographical ancestry. Brazilian population is characterized by a genetic background of three parental populations (European, African, and Brazilian Native Amerindians) with a wide degree and diverse patterns of admixture. In this work we analyzed the information content of 28 ancestry‐informative SNPs into multiplexed panels using three parental population sources (African, Amerindian, and European) to infer the genetic admixture in an urban sample of the five Brazilian geopolitical regions. The SNPs assigned apart the parental populations from each other and thus can be applied for ancestry estimation in a three hybrid admixed population. Data was used to infer genetic ancestry in Brazilians with an admixture model. Pairwise estimates of F_st among the five Brazilian geopolitical regions suggested little genetic differentiation only between the South and the remaining regions. Estimates of ancestry results are consistent with the heterogeneous genetic profile of Brazilian population, with a major contribution of European ancestry (0.771) followed by African (0.143) and Amerindian contributions (0.085). The described multiplexed SNP panels can be useful tool for bioanthropological studies but it can be mainly valuable to control for spurious results in genetic association studies in admixed populations. Am. J. Hum. Biol., 2010. © 2009 Wiley‐Liss, Inc.     

Book review of Encyclopedia of Evolution. Edited by Mark Pagel. (Oxford: Oxford University Press, 2002), 2 vols [ pp. 1234]. ISBN: 0-19-512200-3. £200 hdbk.

The Brazilian population is highly heterogeneous as a result of five centuries of inter-ethnic mating between native Amerindians, European colonizers and Africans arrived during slavery. This study aimed to assess the proportions of inter-ethnic admixture in the Brazilian population of Rio de Janeiro using autosomal Ancestry-Informative Markers (AIMs). The autosomal data were also compared to the results expected from uniparental genetic markers. A total of 413 individuals were genotyped for 46 AIM-Indels and ancestry estimates were then assessed using HGDP-CEPH samples as ancestral reference. Individuals from Rio de Janeiro presented highly diverse admixture patterns. The global admixture estimates showed a predominantly European ancestry, above 55%, followed by African and Amerindian contributions. A separate self-declared Afro-descendant group also included in this study revealed an increased African ancestry, from ～30% to ～50%. The inter-ethnic admixture landscape of Rio de Janeiro captured by autosomal AIM-Indels is in agreement with historical records and similar to that expected from uniparental mtDNA and Y-chromosome information. The AIM-Indel panel proved to be a rapid strategy to estimate autosomal genetic ancestry at individual and population levels in Rio de Janeiro, which is useful in population genetics and in case-control association studies.     

Genetic relationship of the Guambino, Paez, and Ingano Amerindians of southwest Colombia using major histocompatibility complex class II haplotypes and blood groups.

We analyzed the Amerindian tribes, Guambiano, Ingano, and Paez of the southwest section of Colombia by major histocompatibility complex class II typing and blood group analysis in order to establish their genetic relationship. In addition, genetic admixture with Caucasian and African ancestry were determined based on blood group typing. The Paez showed admixture with Caucasian populations (22.4%), while the Ingano and Guambiano showed some admixture with Black populations (9.2 and 4.6%, respectively). The Ingano had MHC class II haplotypes found mainly in Amerindian and Asian populations with no evidence of class II haplotypes of African origin. MHC class II haplotypes of Amerindian and Asian populations and some haplotypes frequently found in European Caucasians and Asians and haplotypes of European Caucasians were found in Guambiano and Paez tribes. We compared our results with those previously reported for four Amerindian tribes on Northern Colombia. The presence of some MHC class II haplotypes in the Guambiano, Paez, and Ingano tribes and their absence in the Chibcha speaking groups of Northern Colombia suggest that these tribes originated, together with other Amerindians, from a separate migration or by genetic drift from an ancestral population. Therefore they are genetically distant from Chibcha speaking tribes of Colombia.     

Y-chromosome genetic variation in Rio de Janeiro population.

The present-day Brazilian gene pool is known to be the outcome of an admixture process of populations from different origins, mainly Amerindians, Europeans, and Africans. It is also known that in Brazil, a wide variation in the admixture process occurred in different regions of the country or even in different subpopulations from the same region. In the present study, we aimed to characterize the male lineages present in the Rio de Janeiro population, the second most populated of the 26 Brazilian states. A random sample of 127 unrelated males from Rio de Janeiro was typed for 28 Y-chromosome-specific biallelic markers. In total, 17 different haplogroups were defined within our sample, most of them of European ancestry (88.1%). Those of sub-Saharan African origin (E3a) amounted to 7.9%, while only 2 males carried Amerindian lineages (characterized by the presence of an M3 mutation: haplogroup Q3). Using both Y-STR haplotype and Y-SNP haplogroup information, genetic distances were calculated between the subgroup of Rio de Janeiro males carrying European haplogroups and the Portuguese population. Low, nonsignificant, values were obtained. Thus, in contrast with what is observed in their female counterparts, the vast majority of the present Rio de Janeiro male gene pool is of European extraction, while the original Amerindian lineages are residual and much less frequent than the sub-Saharan component resulting from the slave trade. These observations can be interpreted as the signature of the strong gender asymmetry of the admixture processes in colonial systems.     

Estimates of interethnic admixture in the Brazilian population using a panel of 24 X‐linked insertion/deletion markers

Objectives. In this study, we aimed to identify ancestry informative haplotypes and make interethnic admixture estimates using X‐chromosome markers. Methods. A significant sample (461 individuals) of European, African, and Native American populations was analyzed, and four linkage groups were identified. The data obtained were used to describe the ancestral contribution of populations from four different geographical regions of Brazil (745 individuals). Results. The global interethnic admixture estimates of the four mixed populations under investigation were calculated applying all the 24 insertion/deletion (INDEL) markers. In the North region, a larger Native Americans ancestry was observed (42%). The Northeast and Southeast regions had smaller Native American contribution (27% in both of them). In the South region, there was a large European contribution (46%). Conclusions. The estimates obtained are compatible with expectations for a colonization model with biased admixture between European men (one X chromosome) and Native American and African women (two X chromosomes), so the 24 X‐INDEL panel described here can be a useful to make admixture interethnic estimates in Brazilian populations. Am. J. Hum. Biol., 2010. © 2010 Wiley‐Liss, Inc.     

Evaluating self-declared ancestry of U.S. Americans with autosomal, Y-chromosomal and mitochondrial DNA

The current U.S. population represents an amalgam of individuals originating mainly from four continental regions (Africa, Europe, Asia and America). To study the genetic ancestry and compare with self-declared ancestry we have analyzed paternally, maternally and bi-parentally inherited DNA markers sensitive for indicating continental genetic ancestry in all four major U.S. American groups. We found that self-declared U.S. Hispanics and U.S. African Americans tend to show variable degrees of continental genetic admixture among the three genetic systems, with evidence for a marked sex-biased admixture history. Moreover, for these two groups we observed significant regional variation across the country in genetic admixture. In contrast, self-declared U.S. European and U.S. Asian Americans were genetically more homogeneous at the continental ancestry level. Two autosomal ancestry-sensitive markers located in skin pigmentation candidate genes showed significant differences in self-declared U.S. African Americans or U.S. European Americans, relative to their assumed parental populations from Africa or Europe. This provides genetic support for the importance of skin color in the complex process of ancestry identification.     

Impact of population admixture on the distribution of immune response co-stimulatory genes polymorphisms in a Brazilian population

Co-stimulatory molecules are essential in the orchestration of immune response and polymorphisms in their genes are associated with various diseases. However, in the case of variable allele frequencies among continental populations, this variation can lead to biases in genetic studies conducted in admixed populations such as those from Brazil. The aim of this study was to evaluate the influence of genomic ancestry on distributions of co-stimulatory genes polymorphisms in an admixed Brazilian population. A total of 273 individuals from the north of Brazil participated in this study. Nine single nucleotide polymorphisms in 7 genes (CD28, CTLA4, ICOS, CD86, CD40, CD40L and BLYS) were determined by polymerase chain reaction-restriction fragment length polymorphism. We also investigated 48 insertion/deletion ancestry markers to characterize individual African, European and Amerindian ancestry proportions in the samples. The analysis showed that the main contribution was European (43.9%) but also a significant contribution of African (31.6%) and Amerindian (24.5%) ancestry. ICOS, CD40L and CD86 polymorphisms were associated with genomic ancestry. However there were no significant differences in the proportions of ancestry for the other SNPs and haplotypes studied. Our findings reinforce the need to apply AIMs in genetic association studies involving these polymorphisms in the Brazilian population.     

Frequency of twinning in two Costa Rican ethnic groups: An update

Variation in the frequency of twinning among human populations has been presumed to reflect genetic differences. It has been commonly reported that populations of African ancestry have the highest, those of Asian ancestry the lowest, and those of European and Middle‐Eastern ancestry intermediate frequencies of twinning. Populations from the Americas have been reported to have intermediate twinning frequencies, presumably reflecting their admixture. In this context, Madrigal (1994. Am J Hum Biol 6:215–218) reported virtually identical (and high) twinning frequencies in two Costa Rican ethnic groups, one of African, the other of Euro‐Amerindian ancestry. These frequencies were interpreted in light of frequent inter‐ethnic unions, and it was predicted that the two groups would not differ substantially in gene frequencies of several blood enzyme systems. This paper reports the gene frequencies of both groups for such systems. The samples differ significantly for systems that have clearly different frequencies in African and European populations. Given that the groups are actually different in gene frequencies and not homogenous as predicted earlier, the conclusion that twinning frequencies are similar as a result of a similar genetic make up can be questioned. The results challenge the assumption that if populations have similar twinning frequencies it is because they are genetically similar and argue for a stronger environmental component for twinning frequencies. Am. J. Hum. Biol. 13:220–226, 2001. © 2001 Wiley‐Liss, Inc.     

Assessing individual interethnic admixture and population substructure using a 48–insertion‐deletion (INSEL) ancestry‐informative marker (AIM) panel

Estimating the proportions of different ancestries in admixed populations is very important in population genetics studies, and it is particularly important for detecting population substructure effects in case‐control association studies. In this work, a set of 48 ancestry‐informative insertion‐deletion polymorphisms (INDELs) were selected with the goal of efficiently measuring the proportions of three different ancestries (sub‐Saharan African, European, and Native American) in mixed populations. All selected markers can be easily analyzed via multiplex PCR and detected with standard capillary electrophoresis. A total of 593 unrelated individuals representative of European, African, and Native American parental populations were typed, as were 380 individuals from three Brazilian populations with known admixture patterns. As expected, the interethnic admixture estimates show that individuals from southern Brazil present an almost exclusively European ancestry; Afro‐descendant communities in the Amazon region, apart from the major African contribution, present some degree of admixture with Europeans and Native Americans; and a sample from Belém, in the northeastern Amazon, shows a significant contribution of the three ethnic groups, although with a greater European proportion. In summary, a panel of ancestry‐informative INDELs was optimized and proven to be a valuable tool for estimating individual and global ancestry proportions in admixed populations. The ability to accurately infer interethnic admixtures highlights the usefulness of this marker set for assessing population substructure in association studies, particularly those conducted in Brazilian and other Latin American populations sharing trihybrid ancestry patterns. Hum Mutat 31:184–190, 2010. © 2009 Wiley‐Liss, Inc.     

Admixture estimates for the population of Havana City

Background: The Cuban population is essentially a result of the admixture between Spanish, West African and, to a lesser degree, Amerindian tribes that inhabited the island.

Aim: The study analysed the genetic structure of the three principal ethnic groups from Havana City, and the contribution of parental populations to its genetic pool.

Subjects and methods: According to genealogical information and anthropological traits, 206 subjects were classified as Mulatto, of Spanish decent or of African descent. Seventeen Ancestry Informative Markers, with high difference in frequency between parental populations, were selected to estimate individual and group admixture proportions. The statistical analyses were performed using the ADMIX, ADMIX95 and STRUCTURE 2.1 packages.

Results: The results demonstrate a high level of European and African admixture in Mulattos (57–59% European; 41–43% West African). The European contribution was higher in those of Spanish descent (85%) while in those of African descent, the West African contribution ranged between 74% and 76%. Genetic structure was only detected in Mulattos and those of African descent. An Amerindian contribution was not detectable in the studied sample.

Conclusion: Our findings indicate the existence of admixture and genetic structure in the population of Havana City. This study represents one of the first steps towards understanding Cuban population admixture in order to produce successful experimental designs for admixture mapping.     

Genome-wide detection of natural selection in African Americans pre- and post-admixture

It is particularly meaningful to investigate natural selection in African Americans (AfA) due to the high mortality their African ancestry has experienced in history. In this study, we examined 491,526 autosomal single nucleotide polymorphisms (SNPs) genotyped in 5210 individuals and conducted a genome-wide search for selection signals in 1890 AfA. Several genomic regions showing an excess of African or European ancestry, which were considered the footprints of selection since population admixture, were detected based on a commonly used approach. However, we also developed a new strategy to detect natural selection both pre- and post-admixture by reconstructing an ancestral African population (AAF) from inferred African components of ancestry in AfA and comparing it with indigenous African populations (IAF). Interestingly, many selection-candidate genes identified by the new approach were associated with AfA-specific high-risk diseases such as prostate cancer and hypertension, suggesting an important role these disease-related genes might have played in adapting to a new environment. CD36 and HBB, whose mutations confer a degree of protection against malaria, were also located in the highly differentiated regions between AAF and IAF. Further analysis showed that the frequencies of alleles protecting against malaria in AAF were lower than those in IAF, which is consistent with the relaxed selection pressure of malaria in the New World. There is no overlap between the top candidate genes detected by the two approaches, indicating the different environmental pressures AfA experienced pre- and post-population admixture. We suggest that the new approach is reasonably powerful and can also be applied to other admixed populations such as Latinos and Uyghurs.     

Population structure and admixture in Cerro Largo, Uruguay, based on blood markers and mitochondrial DNA polymorphisms.

Recent studies of the Uruguayan population revealed different amounts of Amerindian and African genetic contributions. Our previous analysis of Afro-Uruguayans from the capital city of the Department of Cerro Largo showed a high proportion of African genes, and the effects of directional mating involving Amerindian women. In this paper, we extended the analysis to a sample of more than 100 individuals representing a random sample of the population of the whole Department. Based on 18 autosomal markers and one X-linked marker, we estimated 82% European, 8% Amerindian, and 10% African contributions to their ancestry, while from seven mitochondrial DNA site-specific polymorphic markers and sequences of hypervariable segment I, we determined 49% European, 30% Amerindian, and 21% African maternal contributions. Directional matings between Amerindian women and European men were detected, but differences involving Africans were not significant. Data about the specific origins of maternal lineages were also provided, and placed in a historical context.     

Founder mutations in the LDL receptor gene contribute significantly to the familial hypercholesterolemia phenotype in the indigenous South African population of mixed ancestry.

The South African population harbors genes that are derived from varying degrees of admixture between indigenous groups and immigrants from Europe and the East. This study represents the first direct mutation-based attempt to determine the impact of admixture from other gene pools on the familial hypercholesterolemia (FH) phenotype in the recently founded Coloured population of South Africa, a people of mixed ancestry. A cohort of 236 apparently unrelated patients with clinical features of FH was screened for a common mutation causing familial defective apolipoprotein B-100 (FDB) and seven low-density lipoprotein receptor (LDLR) gene defects known to be relatively common in South Africans with FH. Six founder-type 'South African mutations' were responsible for FH in approximately 20% of the study population, while only 1 patient tested positive for the familial defective apolipoprotein B-100 mutation R3500Q. The detection of multiple founder-type LDLR gene mutations originating from European, Indian and Jewish populations provides direct genetic evidence that Caucasoid admixture contributes significantly to the apparently high prevalence of FH in South African patients of mixed ancestry. This study contributes to our knowledge of the biological history of this unique population and illustrates the potential consequences of recent admixture in populations with different disease risks.     

Admixture estimates for Churuguara, a Venezuelan town in the State of Falcón

BACKGROUND: The present Venezuelan population is the admixture product of Amerindians, Europeans and Africans, a process which was not homogeneous over the country. Blood groups, STRs and VNTRs, specifically D1S80, have been used successfully in admixture studies, but few have been made in Venezuela. AIM: This study aims to estimate the admixture components of Churuguara, Venezuela, and to evaluate the genetic relationship of this population with other Venezuelan as well as worldwide populations through principal component analysis and the study of dendrograms based on genetic distances. SUBJECTS AND METHODS: Gene frequencies of blood groups ABO and Rh (only anti D), of STRs VWA, F13A01, FES/FPS and VNTR D1S80 were studied in a sample of 60 individuals born in Churuguara, a Venezuelan town of admixed ancestry in the State of Falc6n. Admixture was estimated with Chakraborty's gene identity method, and Nei's standard genetic distance was used to build two dendrograms with the neighbour-joining approach, one based on the three STRs and the other based only on D1S80. Principal component analyses with the gene frequencies of these markers were also performed. RESULTS: The frequency of allele ABO*O was 0.788, of ABO*A was 0.187 and of RH*D was 0.74. D1S80 showed 16 different alleles with a heterozygosity of 0.880, whilst the three STRs showed only eight different alleles and heterozygosities between 0.733 and 0.797. The estimates of admixture obtained in this analysis were 52.5% for the Spanish parental group, 27.6% for the African and 19.9% for the Amerindian. Comparison of Churuguara with other Latin American populations shows that its African component is not as high as that observed in Colombian Choco, but it is higher than that observed in other samples from Colombia, Chile and Maracaibo (Venezuela). CONCLUSIONS: Results of the admixture analysis are consistent with those obtained with two dendrograms and principal component analyses, suggesting that the strong initial Amerindian component of 500 years ago has been diluted by the continuous flow of European genes, mainly Spanish, to this region.     

Facial clefting and Amerindian admixture in populations of Santiago,Chile

Among congenital malformations, cleft lip with and/or without cleft palate has the highest relative frequencies and shows ethnic variation in prevalence. Both malformations are generally more common among the Asian than European populations. Many populations of Chile have genes of Amerindian and Spanish ancestry, with considerable variation in the degree of Amerindian admixture. Therefore, the association of clefting incidence with Amerindian admixture was investigated. The frequency of cleft lip and/or cleft palate in infants born in three private and two public maternity service clinics of Santiago, Chile, is reported. The private clinic patients have a higher socioeconomic status (SES) than those receiving the public services. They also differ in estimated Amerindian admixture. More than 200,900 consecutive birth records were reviewed. The rate of clefting malformations is 15.3 per 10,000 live births. Based on allele frequencies at the ABO and Rh blood group loci, the percentage of Amerindian admixture is higher in infants born in the public compared to those born in the private maternity service clinics. Amerindian admixture is positively correlated (Spearman's p = 0.9, P = 0.008) with clefting rate across these samples. Clefting is also associated with SES, with lower SES showing higher clefting rates. Mothers of clefting newborns also have higher estimated Amerindian admixture compared to those of normal newborns. The results support the view that in Chilean populations, susceptibility to clefting is related to Amerindian ancestry. Am. J. Hum. Biol. 9:225–232, 1997. © 1997 Wiley-Liss, Inc.     

A panel of ancestry informative markers for estimating individual biogeographical ancestry and admixture from four continents: utility and applications

Autosomal ancestry informative markers (AIMs) are useful for inferring individual biogeographical ancestry (I-BGA) and admixture. Ancestry estimates obtained from Y and mtDNA are useful for reconstructing population expansions and migrations in our recent past but individual genomic admixture estimates are useful to test for association of admixture with phenotypes, as covariate in association studies to control for stratification and, in forensics, to estimate certain overt phenotypes from ancestry. We have developed a panel of 176 autosomal AIMs that can effectively distinguish I-BGA and admixture proportions from four continental ancestral populations: Europeans, West Africans, Indigenous Americans, and East Asians. We present allele frequencies for these AIMs in all four ancestral populations and use them to assess the global apportionment of I-BGA and admixture diversity among some extant populations. We observed patterns of apportionment similar to those described previously using sex and autosomal markers, such as European admixture for African Americans (14.3%) and Mexicans (43.2%), European (65.5%) and East Asian affiliation (27%) for South Asians, and low levels of African admixture (2.8-10.8%) mirroring the distribution of Y E3b haplogroups among various Eurasian populations. Using simulation studies and pedigree analysis we show that I-BGA estimates obtained using this panel and a four-population model has a high degree of precision (average root mean square error [RMSE]=0.026). Using ancestry-phenotype associations we demonstrate that a large and informative AIM panel such as this can help reduce false-positive and false-negative associations between phenotypes and admixture proportions, which may result when using a smaller panel of less informative AIMs.     

Admixture and Population Stratification in African Caribbean Populations

Throughout biomedical research, there is growing interest in the use of ancestry informative markers (AIMs) to deconstruct racial categories into useful variables. Studies on recently admixed populations have shown significant population substructure due to differences in individual ancestry; however, few studies have examined Caribbean populations. Here we used a panel of 28 AIMs to examine the genetic ancestry of 298 individuals of African descent from the Caribbean islands of Jamaica, St. Thomas and Barbados. Differences in global admixture were observed, with Barbados having the highest level of West African ancestry (89.6%± 2.0) and the lowest levels of European (10.2%± 2.2) and Native American ancestry (0.2%± 2.0), while Jamaica possessed the highest levels of European (12.4%± 3.5) and Native American ancestry (3.2%± 3.1). St. Thomas, USVI had ancestry levels quite similar to African Americans in continental U.S. (86.8%± 2.2 West African, 10.6%± 2.3 European, and 2.6%± 2.1 Native American). Significant substructure was observed in the islands of Jamaica and St. Thomas but not Barbados (K=1), indicating that differences in population substructure exist across these three Caribbean islands. These differences likely stem from diverse colonial and historical experiences, and subsequent evolutionary processes. Most importantly, these differences may have significant ramifications for case-control studies of complex disease in Caribbean populations.     

Putative ancestral origins of chromosomal segments in individual african americans: implications for admixture mapping

Theoretically, markers that distinguish European from West African ancestry can be used to examine the origin of chromosomal segments in individual African Americans. In this study, putative ancestral origin was examined by using haplotypes estimated from genotyping 268 African Americans for 29 ancestry informative markers spaced over a 60-cM segment of chromosome 5. Analyses using a Bayesian algorithm (STRUCTURE) provided evidence that blocks of individual chromosomes derive from one or the other parental population. In addition, modeling studies were performed by using hidden real marker data to simulate patient and control populations under different genotypic risk ratios. Ancestry analysis showed significant results for a genotypic risk ratio of 2.5 in the African American population for modeled susceptibility genes derived from either putative parental population. These studies suggest that admixture mapping in the African American population can provide a powerful approach to defining genetic factors for some disease phenotypes.