Native American gene flow into Polynesia predating Easter Island settlement.

The possibility of voyaging contact between prehistoric Polynesian and Native American populations has long intrigued researchers. Proponents have pointed to the existence of New World crops, such as the sweet potato and bottle gourd, in the Polynesian archaeological record, but nowhere else outside the pre-Columbian Americas1-6, while critics have argued that these botanical dispersals need not have been human mediated7. The Norwegian explorer Thor Heyerdahl controversially suggested that prehistoric South American populations had an important role in the settlement of east Polynesia and particularly of Easter Island (Rapa Nui)2. Several limited molecular genetic studies have reached opposing conclusions, and the possibility continues to be as hotly contested today as it was when first suggested8-12. Here we analyse genome-wide variation in individuals from islands across Polynesia for signs of Native American admixture, analysing 807 individuals from 17 island populations and 15 Pacific coast Native American groups. We find conclusive evidence for prehistoric contact of Polynesian individuals with Native American individuals (around AD 1200) contemporaneous with the settlement of remote Oceania13-15. Our analyses suggest strongly that a single contact event occurred in eastern Polynesia, before the settlement of Rapa Nui, between Polynesian individuals and a Native American group most closely related to the indigenous inhabitants of present-day Colombia.

Genetic evidence for two founding populations of the Americas.

Genetic studies have consistently indicated a single common origin of Native American groups from Central and South America. However, some morphological studies have suggested a more complex picture, whereby the northeast Asian affinities of present-day Native Americans contrast with a distinctive morphology seen in some of the earliest American skeletons, which share traits with present-day Australasians (indigenous groups in Australia, Melanesia, and island Southeast Asia). Here we analyse genome-wide data to show that some Amazonian Native Americans descend partly from a Native American founding population that carried ancestry more closely related to indigenous Australians, New Guineans and Andaman Islanders than to any present-day Eurasians or Native Americans. This signature is not present to the same extent, or at all, in present-day Northern and Central Americans or in a ∼12,600-year-old Clovis-associated genome, suggesting a more diverse set of founding populations of the Americas than previously accepted.

Genetic diversity, structure, and admixture in Mayans from Guatemala and Mexico based on 15 short tandem repeats.

OBJECTIVE: To analyze the genetic origin, relationships, structure, and admixture in Mayan Native American groups from Guatemala and Mexico based on 15 autosomal short tandem repeats (STRs) loci commonly used in human identification (HID). METHODS: We genotyped 513 unrelated Mayan samples from Guatemala based on 15 STR loci (AmpFlSTR® Identifiler kit). Moreover, we included 4408 genotypes previously reported, as following: Mayas from Guatemala and Mexico (n = 1666) and from Latin American, European, and African (n = 2742) populations. Forensic parameters, genetic distances, admixture, and population structure were assessed. RESULTS: Forensic parameters of the 15 STRs in different Mayan groups from Guatemala were reported. Low (Fst = 0.78%; p = 0.000) and non-significant differentiation (Fst = 1.8%; p = 0.108) were observed in Mayas from Guatemala and Mexico, respectively. The relative homogeneity observed among Mayan groups supported theories of extensive pre-Columbian gene flow and trade throughout the Mayan Empire. The distribution of the three Native American ancestries among these Mayan groups did not support the presumable Guatemalan origin of Tojolabal and Lacandon people (South, Mexico). The nonsignificant differentiation between Ladinos and Mayas suggests a relative panmixia in Guatemala. Mestizos from southeastern Mexico and Guatemala constitute a core of Native American ancestry in Latin America related to the Mayan Empire in Central America. CONCLUSIONS: The higher European admixture and homogeneity in Mexican Mayas of the Yucatan Peninsula suggest more intensive post-Columbian gene flow in this region than in Guatemalan Mayas.

The distribution in native populations from Mexico and Central America of the C677T variant in the MTHFR gene.

OBJECTIVES: To explore evolutionary hypotheses for the high frequencies of a substitution in the methylenetetrahydrofolate reductase (MTHFR) gene, in Mexican and Central American Indigenous populations. MATERIALS AND METHODS: We obtained allele frequencies for the C677T variant in the MTHFR gene and ecological information for 37 indigenous samples from Mexico and Central America. We calculated Hardy-Weinberg equilibrium and computed Fst statistics. We computed correlations between the samples' allele frequencies and ecological and geochemical variables. RESULTS: Many of the samples have extremely high frequencies of the T allele ( q ¯  = 0.62, median = 0.66). In this region, the frequency of the T allele decreases from Southeast to Northwest and is significantly correlated with longitude, latitude, altitude, and insolation. CONCLUSIONS: The native people of Central America and Mexico evolved high frequencies of an allele which has been shown to produce deleterious clinical effects including neural tube effects, cardiovascular events, and cancer. This allele has a clinal distribution in the region, perhaps associated with solar irradiation. As (Contreras-Cubas et al., 2016) noted, the traditional diet of these populations, which is high in folate, has likely mitigated the negative effect of the allele. It is of primary importance that their rights to their homeland and traditional diets be respected. It is a matter of Public Health to investigate whether this allele is a factor in the current wave of cardiovascular diseases affecting the majority population of this region, since it descends from the Native peoples and the Mediterranean population, which also has high frequencies of the allele.

Association of genetic ancestry with colorectal tumor location in Puerto Rican Latinos.

BACKGROUND: Colorectal cancer (CRC) is the first cause of cancer deaths among Puerto Ricans. The incidence and mortality of CRC in Puerto Rico continue to be on the rise. The burden of CRC in Puerto Rico is higher than among US Hispanics and is second only to African Americans, thus supporting the importance of studying this CRC health disparity. The genetic background of the Puerto Rican population is a mix of European, African, and Amerindian races, which may account, in part, for the differences observed in the CRC mortality rates among Puerto Ricans. The objective of the study was to assess the role of genetic ancestry in CRC risk and its association with clinicopathological features of CRC tumors in Puerto Ricans. RESULTS: We used a validated panel of 105 ancestry informative markers (AIMs) to estimate genetic ancestry in 406 Puerto Rican CRC cases and 425 Puerto Rican controls. We examined the association of genetic ancestry with CRC risk and tumor clinicopathological characteristics. CONCLUSIONS: The mean ancestry proportions in the study population were 61% European, 21% African, and 18% Amerindian. No association was observed between genetic ancestry and risk of CRC. However, African ancestry was associated with an increased risk of developing rectal tumors (OR = 1.55, 95% CI 1.04-2.31). Additional studies are needed to fully elucidate the role of African ancestry in CRC carcinogenesis.

Genetic signature of natural selection in first Americans.

When humans moved from Asia toward the Americas over 18,000 y ago and eventually peopled the New World they encountered a new environment with extreme climate conditions and distinct dietary resources. These environmental and dietary pressures may have led to instances of genetic adaptation with the potential to influence the phenotypic variation in extant Native American populations. An example of such an event is the evolution of the fatty acid desaturases (FADS) genes, which have been claimed to harbor signals of positive selection in Inuit populations due to adaptation to the cold Greenland Arctic climate and to a protein-rich diet. Because there was evidence of intercontinental variation in this genetic region, with indications of positive selection for its variants, we decided to compare the Inuit findings with other Native American data. Here, we use several lines of evidence to show that the signal of FADS-positive selection is not restricted to the Arctic but instead is broadly observed throughout the Americas. The shared signature of selection among populations living in such a diverse range of environments is likely due to a single and strong instance of local adaptation that took place in the common ancestral population before their entrance into the New World. These first Americans peopled the whole continent and spread this adaptive variant across a diverse set of environments.

Distance from sub-Saharan Africa predicts mutational load in diverse human genomes.

The Out-of-Africa (OOA) dispersal ∼ 50,000 y ago is characterized by a series of founder events as modern humans expanded into multiple continents. Population genetics theory predicts an increase of mutational load in populations undergoing serial founder effects during range expansions. To test this hypothesis, we have sequenced full genomes and high-coverage exomes from seven geographically divergent human populations from Namibia, Congo, Algeria, Pakistan, Cambodia, Siberia, and Mexico. We find that individual genomes vary modestly in the overall number of predicted deleterious alleles. We show via spatially explicit simulations that the observed distribution of deleterious allele frequencies is consistent with the OOA dispersal, particularly under a model where deleterious mutations are recessive. We conclude that there is a strong signal of purifying selection at conserved genomic positions within Africa, but that many predicted deleterious mutations have evolved as if they were neutral during the expansion out of Africa. Under a model where selection is inversely related to dominance, we show that OOA populations are likely to have a higher mutation load due to increased allele frequencies of nearly neutral variants that are recessive or partially recessive.

Ancient mitochondrial DNA and ancestry of Paquimé inhabitants, Casas Grandes (A.D. 1200-1450).

OBJECTIVES: The Casas Grandes (Paquimé) culture, located in the Northwest of Chihuahua, Mexico reached its apogee during the Medio Period (A.D. 1200-1450). Paquimé was abandoned by the end of the Medio Period (A.D. 1450), and the ancestry of its inhabitants remains unsolved. Some authors suggest that waves of Mesoamerican immigrants, possibly merchants, stimulated Paquimé's development during the Medio Period. Archaeological evidence suggests possible ties to groups that inhabited the Southwestern US cultures. This study uses ancient DNA analysis from fourteen samples to estimate genetic affinities of ancient Paquimé inhabitants. MATERIALS AND METHODS: DNA was extracted from 14 dental ancient samples from Paquimé. PCR and Sanger sequencing were used to obtain mitochondrial control region sequences. Networks, PCoA, and Nei genetic distances were estimated to compare Paquimé haplotypes against available past haplotypes data from Southwestern and Mesoamerican groups. RESULTS: Haplogroups were characterized for 11 of the samples, and the results revealed the presence of four distinct Amerindian mitochondrial lineages: B (n = 5; 45%), A (n = 3; 27%), C (n = 2; 18%) and D (n = 1; 10%). Statistical analysis of the haplotypes, haplogroup frequencies, and Nei genetic distances showed close affinity of Paquimé with Mimbres. DISCUSSION: Although our results provide strong evidence of genetic affinities between Paquimé and Mimbres, with the majority of haplotypes shared or derived from ancient Southwest populations, the causes of cultural development at Paquimé still remain a question. These preliminary results provide evidence in support of other bioarchaeological studies, which have shown close biological affinities between Paquimé and Mimbres, a Puebloan culture, in the Southwestern US.

Analysis of 16 autosomal STRs and 17 Y-STRs in an indigenous Maya population from Guatemala.

The aim of this study was to contribute new data on autosomal STR and Y-STR markers of the Mayas from Guatemala in order to improve available databases of forensic interest. We analyzed 16 autosomal STR markers in a population sample of 155 indigenous Maya and 17 Y-chromosomal STR markers in the 100 males of the sample. Deviations from Hardy-Weinberg equilibrium and linkage disequilibrium between autosomal STR markers were not observed at any loci. The combined power of exclusion was estimated as 99.9991% and the combined power of discrimination was >99.999999999999%. Haplotype diversity of Y-STRs was calculated as 0.9984 ± 0.0018 and analysis of pairwise genetic distances (Rst) supported the Native American background of the population.

Genetic Affiliation of Pre-Hispanic and Contemporary Mayas Through Maternal Linage.

Maya civilization developed in Mesoamerica and encompassed the Yucatan Peninsula, Guatemala, Belize, part of the Mexican states of Tabasco and Chiapas, and the western parts of Honduras and El Salvador. This civilization persisted approximately 3,000 years and was one of the most advanced of its time, possessing the only known full writing system at the time, as well as art, sophisticated architecture, and mathematical and astronomical systems. This civilization reached the apex of its power and influence during the Preclassic period, from 2000 BCE to 250 CE. Genetic variation in the pre-Hispanic Mayas from archaeological sites in the Mexican states of Yucatan, Chiapas, Quintana Roo, and Tabasco and their relationship with the contemporary communities in these regions have not been previously studied. Consequently, the principal aim of this study was to determine mitochondrial DNA (mtDNA) variation in the pre-Hispanic Maya population and to assess the relationship of these individuals with contemporary Mesoamerican Maya and populations from Asia, Beringia, and North, Central, and South America. Our results revealed interactions and gene flow between populations in the different archaeological sites assessed in this study. The mtDNA haplogroup frequency in the pre-Hispanic Maya population (60.53%, 34.21%, and 5.26% for haplogroups A, C, and D, respectively) was similar to that of most Mexican and Guatemalan Maya populations, with haplogroup A exhibiting the highest frequency. Haplogroup B most likely arrived independently and mixed with populations carrying haplogroups A and C based on its absence in the pre-Hispanic Mexican Maya populations and low frequencies in most Mexican and Guatemalan Maya populations, although this also may be due to drift. Maya and Ciboneys sharing haplotype H10 belonged to haplogroup C1 and haplotype H4 of haplogroup D, suggesting shared regional haplotypes. This may indicate a shared genetic ancestry, suggesting more regional interaction between populations in the circum-Caribbean region than previously demonstrated. Haplotype sharing between the pre-Hispanic Maya and the indigenous populations from Asia, the Aleutian Islands, and North, Central, and South America provides evidence for gene flow from the ancestral Amerindian population of the pre-Hispanic Maya to Central and South America.

Population History and Mitochondrial Genetic Substructure of the Rama Amerindians from Nicaragua.

The Rama are a coastal population from southern Nicaragua who in large part were able to resist, at least for a time, the cultural changes and social reorganization brought on by colonial and modern influences. Historical information leaves the Rama origins and biological relationships with nearby extinct and extant groups ambiguous. The objective of this study was to examine the internal genetic microdifferentiation based on the first hypervariable region of the mitochondrial DNA (mtDNA) from a sample of approximately 20% of the population, and to expand the few available historical and anthropological data on the Rama by exploring the effects of cultural practices and historical events on genetic structure, providing an integrative perspective on the Rama genetic history. When considering differences in the spatial distribution and genetic diversity of the mtDNA haplotypes together with historical information on the Rama, a noteworthy pattern emerges. (a) Haplotypes are differentially distributed among a central Rama community (Punta Águila) compared with the other five peripheral communities (analysis of molecular variance: FCT = 0.10, p < 0.001), and their distribution is consistent with the historical relocation of this population after their split from Punta Gorda in the 18th century. (b) Differential genetic signatures found among central and peripheral Rama communities resemble two population histories: one of stability (haplogroup A2) and other of expansion (haplogroup B2), supporting the possibility that these patterns of genetic microdifferentiation between central and peripheral populations resulted from the 18th-century unification in southern Nicaragua of the Rama and a group of Voto migrants from Costa Rica that later split off and moved to the Bay of Bluefields.

Effect of recent historical events on migration and isonymic stratification among the Rama Amerindians from Nicaragua.

The Rama Amerindians from southern Nicaragua are one of few indigenous populations inhabiting the east coast and lowlands of southern Central America. Early-eighteenth-century ethnohistorical accounts depicted the Rama as a mobile hunter-gatherer and horticulturalist group dispersed in household units along southern Nicaraguan rivers. However, during the nineteenth and twentieth centuries, Rama settlement patterns changed to aggregated communities because of increased competition for local resources resulting from nonindigenous immigration. The objective of this study was to discern the degree of relatedness between and within subdivisions of seven of these communities based on patterns of surname variation and genealogical data. We applied surname analyses (n = 592) to evaluate inter- and intrapopulation variation, consanguinity and substructure estimates, and isolation by distance and used a genealogically based marital migration matrix obtained during fieldwork in 2007 and 2009 to better understand internal migration. Our evaluation indicates a pattern of geographic distribution linking kinships in major subpopulations to nearby family-based villages. Mantel tests provide a correlation (r = 0.4; p < 0.05) between distance matrices derived from surname and geography among Rama communities. Genealogical analysis reveals a pattern of kin networks within both peripheral and central populations, consistent with previous genetic investigations, where the Amerindian mitochondrial DNA haplogroup B2 is commonly found among peripheral communities and A2 is frequent in central subpopulations. Marital migration and genealogies provide additional information regarding the influx of non-Ramas to communities near populated villages. These results indicate that the disruption of the Rama's traditional way of life has had significant consequences on their population structure consistent with population fissions and aggregations since the eighteenth century.

Genetic diversity of the HLA-G coding region in Amerindian populations from the Brazilian Amazon: a possible role of natural selection.

HLA-G has an important role in the modulation of the maternal immune system during pregnancy, and evidence that balancing selection acts in the promoter and 3'UTR regions has been previously reported. To determine whether selection acts on the HLA-G coding region in the Amazon Rainforest, exons 2, 3 and 4 were analyzed in a sample of 142 Amerindians from nine villages of five isolated tribes that inhabit the Central Amazon. Six previously described single-nucleotide polymorphisms (SNPs) were identified and the Expectation-Maximization (EM) and PHASE algorithms were used to computationally reconstruct SNP haplotypes (HLA-G alleles). A new HLA-G allele, which originated in Amerindian populations by a crossing-over event between two widespread HLA-G alleles, was identified in 18 individuals. Neutrality tests evidenced that natural selection has a complex part in the HLA-G coding region. Although balancing selection is the type of selection that shapes variability at a local level (Native American populations), we have also shown that purifying selection may occur on a worldwide scale. Moreover, the balancing selection does not seem to act on the coding region as strongly as it acts on the flanking regulatory regions, and such coding signature may actually reflect a hitchhiking effect.

Ancestry informative markers clarify the regional admixture variation in the Costa Rican population.

The genetic structure of Costa Rica's population is complex, both by region and by individual, due to the admixture process that started during the 15th century and historical events thereafter. Previous studies have been done mostly on Amerindian populations and the Central Valley inhabitants using various microsatellites and mitochondrial DNA markers. Here, we study for the first time a random sample from all regions of the country with ancestry informative markers (AIMs) to address the individual and regional admixture proportions. A sample of 160 male individuals was screened for 78 AIMs customized in a GoldenGate platform from Illumina. We observed that this small set of AIMs has the same power of hundreds of microsatellites and thousands of single-nucleotide polymorphisms to evaluate admixture, with the benefit of reducing genotyping costs. This type of investigation is necessary to explore new genetic markers useful for forensic and genetic investigation. Our data showed a mean admixture proportion of 49.2% European (EUR), 37.8% Native American (NAM), and 12.9% African (AFR), with a disproportionate admixture composition by region. In addition, when Chinese (CHB) was included as a fourth component, the proportions changed to 45.6% EUR, 33.5% NAM, 11.7% AFR, and 9.2% CHB. The admixture trend is consistent among all regions (EUR > NAM > AFR), and individual admixture estimates vary broadly in each region. Though we did not find stratification in Costa Rica's population, gene admixture should be evaluated in future genetic studies of Costa Rica, especially for the Caribbean region, as it contains the largest proportion of African ancestry (30.9%).

Microevolution, migration, and the population structure of five Amerindian populations from Nicaragua and Costa Rica.

OBJECTIVE: This research examines the coevolution of languages and uniparental genetic marker (mitochondrial DNA [mtDNA] and nonrecombining Y-chromosome [NRY]) variation within five Lower Central American (Rama, Chorotega, Maléku, Zapatón-Huetar, and Abrojo-Guaymí) Amerindian groups. This pattern occurred since European contact. METHODS: We examined mtDNA sequence variation from the hypervariable region 1 (HVS-1) and NRY genetic variation using short tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, and DYS439) and NRY haplogroups (Q1a3a, Q1a3*, C3b, R1b1b2, E1b1, G2a2, and I) identified through single-nucleotide polymorphisms. Phylogenetic analysis included multidimensional scaling (MDS), heterozygosity versus rii , and analysis of molecular variance (AMOVA). RESULTS: Eighteen mtDNA haplotypes were characterized in 131 participants with 94.6% of these assigned to the Amerindian mtDNA subclades, A2 and B2. The Amerindian NRY haplogroup, Q1a3a, was present in all five groups and ranged from 85% (Zapatón-Huetar) to 35% (Chorotega). Four populations (Rama, Chorotega, Zapatón-Huetar, and Abrojo-Guaymí) were also characterized by the presence of NRY haplogroup R1b1b2 indicative of western European admixture. Seventy NRY STR haplotypes were identified of which 69 (97%) were population specific. MDS plots demonstrated genetic similarities between Mesoamericans and northern Chibchan Amerindian populations, absent in mtDNA analyses, which is further supported by heterozygosity versus rii results. CONCLUSIONS: We conclude that although these linguistically related populations in geographic proximity demonstrate a high degree of paternal genetic differentiation, recent demographic events have dramatically altered the paternal genetic structure of the regions Amerindian populations.

High frequency of Parkin exon rearrangements in Mexican-mestizo patients with early-onset Parkinson's disease.

BACKGROUND: Parkin mutations in patients with early-onset Parkinson's disease (EOPD) are estimated to occur in 49% of familial cases and 18% of sporadic cases. METHODS: We analyzed the entire sequence-coding region and dosage mutations of parkin in 63 Mexican-mestizo EOPD patients and 120 controls. RESULTS: Parkin mutations were present in 34 patients (54.0%). Exon rearrangements, predominantly spanning exons 9 and 12 (31.7% and 19.0%, respectively) were present in 32 patients, with 17.5% carrying simple heterozygous and 25.4% carrying compound heterozygous parkin mutations. CONCLUSIONS: A higher frequency of parkin exon rearrangements than of sequence mutations was observed. Patients with parkin exons 9 and 12 rearrangements showed a later age at onset than did cases with other regions affected (40.3 ± 4.5 vs 30.1 ± 8.8; P = .005), suggesting a mutational hot spot in the etiology of Mexican-mestizo patients with EOPD. To our knowledge, this study represents the largest sampling of Mexican-mestizo patients with EOPD cases for which parkin sequence and dosage alterations were analyzed. .

The genetic impact of Aztec imperialism: ancient mitochondrial DNA evidence from Xaltocan, Mexico.

In AD 1428, the city-states of Tenochtitlan, Texcoco, and Tlacopan formed the Triple Alliance, laying the foundations of the Aztec empire. Although it is well documented that the Aztecs annexed numerous polities in the Basin of Mexico over the following years, the demographic consequences of this expansion remain unclear. At the city-state capital of Xaltocan, 16th century documents suggest that the site's conquest and subsequent incorporation into the Aztec empire led to a replacement of the original Otomí population, whereas archaeological evidence suggests that some of the original population may have remained at the town under Aztec rule. To help address questions about Xaltocan's demographic history during this period, we analyzed ancient DNA from 25 individuals recovered from three houses rebuilt over time and occupied between AD 1240 and 1521. These individuals were divided into two temporal groups that predate and postdate the site's conquest. We determined the mitochondrial DNA haplogroup of each individual and identified haplotypes based on 372 base pair sequences of first hypervariable region. Our results indicate that the residents of these houses before and after the Aztec conquest have distinct haplotypes that are not closely related, and the mitochondrial compositions of the temporal groups are statistically different. Altogether, these results suggest that the matrilines present in the households were replaced following the Aztec conquest. This study therefore indicates that the Aztec expansion may have been associated with significant demographic and genetic changes within Xaltocan.

HLA-class II genes in Mexican Amerindian Mayas: relatedness with Guatemalan Mayans and other populations.

We analyzed the HLA class II allele frequencies in 50 healthy unrelated Mayan individuals. The relationship with other worldwide populations was studied by using HLA data from 71 different populations. The most frequent alleles were HLA-DRB1*04, HLA-DRB1*01, HLA-DQB1*0302 and HLA-DQB1*0501. When comparisons with other Mexican Amerindian groups were made, some differences were observed. Mayans showed an increased frequency of HLA-DRB1*01 when compared to Nahuas, Mayos, Teenek and Mazatecans (p < 0.05), whereas the HLA-DRB1*04 was increased in Mayans when compared to Nahuas (p < 0.05). The analysis of HLA-DQB1 alleles showed an increased frequency of DQB1*0302 in Mayans when compared to Nahuas and Mazatecans (p < 0.05), whereas the frequency of HLA-DQB1*0301 was decreased in Mayans when compared to Nahuas, Mayos, Teenek and Mazatecans (p < 0.05). Decreased frequency of HLA-DQB1*0501 in Mayans when compared to Nahuas was found. Neighbour Joining dendrogram shows that Mexican Mayans are genetically close to some of the most ancient groups living in Mexico and some South American Amerindians. However, Guatemalan Mayans do not cluster together with Mexican Mayas showing that languages do not correlate with genes, particularly in Amerindians. The data corroborate the restricted polymorphism of HLA-DRB1 and DQB1 alleles and the high frequency of HLA-DRB1*04 and HLA-DQB1*0302 in Mayans from Mexico.

X-chromosomal genetic diversity and linkage disequilibrium patterns in Amerindians and non-Amerindian populations.

OBJECTIVES: We report X-chromosomal linkage disequilibrium (LD) patterns in Amerindian (Kogi, Wayuu, and Zenu) and admixed Latin American (Central Valley of Costa Rica and Southern Brazilian Gaucho) populations. METHODS: Short tandem repeats (STRs) widespread along the X-chromosome were investigated in 132 and 124 chromosomes sampled from the Amerindian tribes and the admixed Latin American populations, respectively. Diversity indexes (gene diversity and average numbers of alleles per locus) were estimated for each population and the level of LD was inferred with an exact test. RESULTS: The Amerindian populations presented lower genetic diversity and a higher proportion of loci in LD than the admixed ones. Two haplotype blocks were identified in the X-chromosome, both restricted to the Amerindians. The first involved DXS8051 and DXS7108 in Xp22.22 and Xp22.3, while the second found only among the Kogi, included eight loci in a region between Xp11.4 and Xq21.1. CONCLUSIONS: In accordance to previous work done with other populations, human isolates, such as Amerindian tribes, seem to be an optimal choice for the implementation of association studies due to the wide extent of LD which can be found in their gene pool. On the other hand, the low proportion of loci in LD found in both admixed populations studied here could be explained by events related to their history and similarities between the allele frequencies in the parental stocks.

Genetic risk factors for nonsyndromic cleft lip with or without cleft palate in a Mesoamerican population: Evidence for IRF6 and variants at 8q24 and 10q25.

INTRODUCTION: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common of all birth defects. NSCL/P has a multifactorial etiology that includes both genetic and environmental factors. The IRF6 gene and three further susceptibility loci at 8q24, 10q25, and 17q22, which were identified by a recent genome-wide association scan (GWAS), are confirmed genetic risk factors for NSCL/P in patients of European descent. METHODS: A case-control association study was performed to investigate whether these four risk loci contribute to NSCL/P in a Mesoamerican population using four single nucleotide polymorphisms to represent IRF6 and the three novel susceptibility loci. A total of 149 NSCL/P patients and 303 controls of Mayan origin were included. RESULTS: Single marker analysis revealed a significant association between NSCL/P and risk variants in IRF6 and the 8q24 and 10q25 loci. In contrast to previous findings, the association at the 8q24 locus was driven solely by homozygote carriers of the risk allele. This suggests that this locus might act in a recessive manner in the Mayan population. No evidence for association was found at the 17q22 locus. This may have been attributable to the limited power of the sample. CONCLUSION: These results suggest that IRF6 and the 10q25 and 8q24 loci confer a risk for the development of NSCL/P in persons of Mayan origin.