Maximum likelihood estimates of admixture in northeastern Mexico using 13 short tandem repeat loci

Tetrameric short tandem repeat (STR) polymorphisms are widely used in population genetics, molecular evolution, gene mapping and linkage analysis, paternity tests, forensic analysis, and medical applications. This article provides allelic distributions of the STR loci D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820, CSF1PO, TPOX, TH01, and D16S539 in 143 Mestizos from Northeastern Mexico, estimates of contributions of genes of European (Spanish), American Indian and African origin in the gene pool of this admixed Mestizo population (using 10 of these loci); and a comparison of the genetic admixture of this population with the previously reported two polymorphic molecular markers, D1S80 and HLA‐DQA1 (n = 103). Genotype distributions were in agreement with Hardy‐Weinberg expectations (HWE) for almost all 13 STR markers. Maximum likelihood estimates of admixture components yield a trihybrid model with Spanish, Amerindian, and African ancestry with the admixture proportions: 54.99% ± 3.44, 39.99% ± 2.57, and 5.02% ± 2.82, respectively. These estimates were not significantly different from those obtained using D1S80 and HLA‐DQA1 loci (59.99% ± 5.94, 36.99% ± 5.04, and 3.02% ± 2.76). In conclusion, Mestizos of Northeastern Mexico showed a similar ancestral contribution independent of the markers used for evolutionary purposes. Further validation of this database supports the use of the 13 STR loci along with D1S80 and HLA‐DQA1 as a battery of efficient DNA forensic markers in Northeastern Mestizo populations of Mexico. Am. J. Hum. Biol. 14:429–439, 2002. © 2002 Wiley‐Liss, Inc.     

Genetic structure of Mexican Mestizo women with breast cancer based on three STR loci.

The aim of this population genetics study was to compare the genetic structure of Mexican women with breast cancer (BrCa) with previously reported data of four random populations (Nuevo León, Hispanics, Chihuahua, and Central Region of Mexico). A sample of 115 unrelated women with BrCa and whose four grandparents were born in five zones of Mexico were interviewed at a reference hospital in Northeastern Mexico. Noncodifying STRs D7S820, D13S317, and D16S39 were analyzed; genotype distribution was in agreement with Hardy-Weinberg expectations for all three markers. Similar allele frequencies among four random populations and this selected population were found. According with this and previous studies using molecular and nonmolecular nuclear DNA markers not associated with any disease, Mexican Mestizo population is genetically homogeneous and therefore, genetic causes of BrCa are less heterogeneous, simplifying genetic epidemiologic studies.     

Genetic variation by birth cohorts in Mexican Americans of Starr County,Texas

Mexican Americans residing in Starr County, Texas, were grouped by their year of birth (1896–1925, 1926–1955, and 1956–1985) to determine the extent of birth cohort-related genetic variation within this population and the genetic differences, if any, from the Mexican population residing in the Metropolitan Monterrey Area (MMA), Nuevo León, México. Twenty-one genetic markers were analyzed which indicate that the three birth cohort groups are genetically indistinguishable. Gene diversity analysis suggests that more than 99.8% of the total gene diversity can be attributed to variation between individuals within the birth cohort populations and that the subdivision by birth cohort has only a small contribution (0.18%) to the total gene diversity. Genetic admixture analysis indicates a predominant influence from the Spanish, and that the three birth cohort groups were similar in terms of contributions of this ancestral population. The genetic structure of the Mexican American population of Starr County was also similar to the Mexican population from the State of Nuevo León, México. These findings, together with previous results, suggest that the Mexican Americans of Starr County, Texas, classified by gender, birthplace, and age, are not genetically distinguishable and are similar to the Mexican populations of the State of Nuevo León. © 1994 Wiley-Liss, Inc.     

Prevalence of NIDDM in Mexicans with paraphyletic and polyphyletic surnames

It has been hypothesized that the greater prevalence of non-insulin-dependent diabetes mellitus (NIDDM) in Mexicans may be related to their greater degree of Amerindian genetic admixture (AGA). The aim of this unmatched case–control study was to correlate the prevalence of NIDDM with AGA in 10 Mexican Mestizo populations non-randomly selected by surname. A sample of 1,699 unrelated persons, >44 years and residing in the state of Nuevo León, was selected on the basis of paraphyletic or polyphyletic surnames and interviewed in the Instituto Mexicano del Seguro Social (IMSS). All subjects received a medical examination, and diabetes was diagnosed on the basis of World Health Organization criteria. Three genetic marker systems were analyzed, and the percentage of AGA was calculated. Logistic regression analysis was performed with the prevalence as the dependent variable and sex and surname as the independent variables. The Spearman rank–order correlation analysis was calculated between the age-adjusted prevalence (45–75+ years) and AGA. The correlation revealed a pattern of increasing prevalence of NIDDM with increasing Amerindian ancestry by surname. Am. J. Hum. Biol. 12:721–728, 2000. © 2000 Wiley-Liss, Inc.     

Genetic diversity of HLA system in two populations from Nuevo León,Mexico: Monterrey and rural Nuevo León

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 665 Mexicans from the state of Nuevo León living in the city of Monterrey (N = 226) and rural communities (N = 439), to obtain information regarding allelic and haplotypic frequencies. We find that the most frequent haplotypes in the state of Nuevo León include 12 Native American and three European haplotypes. Admixture estimates revealed that the main genetic components in the state of Nuevo León are Native American (54.53 ± 0.87% by ML; 48.88% of Native American haplotypes) and European (38.67 ± 4.06% by ML; 32.59% of European haplotypes), and a less prominent African genetic component (6.80 ± 4.30% by ML; 8.26% of African haplotypes).     

Prevalence of HLA‐DQA1 alleles and haplotypes in blood donors resident in Wales

Two hundred and fifty‐four normal blood donors, from a largely UK European population, were sequence‐based typed for HLA‐A, HLA‐B, HLA‐C, HLA‐DRB1, HLA‐DQA1 and HLA‐DQB1. The fit to Hardy–Weinberg expectations was good for all loci (all P values >0.5). Fifteen DQA1 alleles were identified to the second field. DQA1 carriage, allele and DQA1–DQB1 and DRB1–DQA1–DQB1 haplotype frequencies, linkage disequilibria and related values are presented.     

Genetic admixture of eight Mexican indigenous populations: Based on five polymarker,HLA‐DQA1, ABO,and RH loci

This study explores the genetic admixture of eight Mexican indigenous populations (Otomi‐Ixmiquilpan, Otomi‐Actopan, Tzeltales, Nahua‐Milpa‐Alta, Nahua‐Xochimilco, Nahua‐Zitlala, Nahua‐Ixhuatlancillo, and Nahua‐Coyolillo) on the basis of five PCR‐based polymorphic DNA loci (LDLR, GYPA, HBGG, D7S8, GC), HLA_DQA1, and the blood groups ABO and Rh (CcDEe). Among the indigenous populations, the highest gene frequencies for O and D were 0.9703 and 1.000 for Zitlala (State of Guerrero) and 0.9955 and 0.9414 for Tzeltales (State of Chiapas), respectively. Maximum likelihood estimates of admixture components yield a trihybrid model with Amerindian (assuming that Nahua‐Zitlala is the most representative indigenous population), Spanish, and African ancestry with the admixture proportions: 93.03, 6.03, and 0.94 for Tzeltales, and 28.99, 44.03, and 26.98 for Coyolillo. A contribution of the ancestral populations of Ixhuatlancillo, Actopan, Ixmiquilpan, Milpa‐Alta, and Xochimilco were found with the following average of admixture proportions: 75.84, 22.50, and 1.66. The findings herein demonstrate that the genetic admixture of the Mexican indigenous populations who at present speak the same Amer‐Indian language can be differentiated and that the majority of them have less ancestral indigenous contribution than those considered as Mestizo populations. Am. J. Hum. Biol., 2008. © 2008 Wiley‐Liss, Inc.     

Hardy-Weinberg testing for HLA class II (DRB1, DQA1, DQB1, and DPB1) loci in 26 human ethnic groups

Testing the fit of population data to Hardy-Weinberg proportions is crucial in the validation of many current approaches in population genetic studies. In this paper, we tested fit to Hardy-Weinberg proportions using exact approaches for both the overall and individual heterozygote genotype data of four HLA Class II loci: DRB1, DQA1, DQB1, and DPB1, from 26 human populations. Eighty of 99 overall tests fit the Hardy-Weinberg expectation (73% for DRB1, 89% for DQA1, 81% for DQB1 and 81% for DPB1). Deviations from Hardy-Weinberg proportions were both locus and group specific. Although we could not rule out other mechanisms at work, the individual test results indicated that the departure was possibly partly due to recent admixture. Evidence for selection and other sources of deviation are also discussed.     

DNA methylation and mRNA expression of HLA‐DQA1 alleles in type 1 diabetes mellitus

Type 1 diabetes (T1D) belongs among polygenic multifactorial autoimmune diseases. The highest risk is associated with human leucocyte antigen (HLA) class II genes, including HLA‐DQA1 gene. Our aim was to investigate DNA methylation of HLA‐DQA1 promoter alleles (QAP) and correlate methylation status with individual HLA‐DQA1 allele expression of patients with T1D and healthy controls. DNA methylation is one of the epigenetic modifications that regulate gene expression and is known to be shaped by the environment.Sixty one patients with T1D and 39 healthy controls were involved in this study. Isolated DNA was treated with sodium bisulphite and HLA‐DQA1 promoter sequence was amplified using nested PCR. After sequencing, DNA methylation of HLA‐DQA1 promoter alleles was analysed. Individual mRNA HLA‐DQA1 relative allele expression was assessed using two different endogenous controls (PPIA, DRA). We have found statistically significant differences in HLA‐DQA1 allele 02:01 expression (PPIA normalization, P_corr = 0·041; DRA normalization, P_corr = 0·052) between healthy controls and patients with T1D. The complete methylation profile of the HLA‐DQA1 promoter was gained with the most methylated allele DQA1*02:01 and the least methylated DQA1*05:01 in both studied groups. Methylation profile observed in patients with T1D and healthy controls was similar, and no correlation between HLA‐DQA1 allele expression and DNA methylation was found. Although we have not proved significant methylation differences between the two groups, detailed DNA methylation status and its correlation with expression of each HLA‐DQA1 allele in patients with T1D have been described for the first time.     

Genetic population history relationships of the population of Bogotá, Colombia,by using the D1S80, VWA,and TH01 molecular markers

The genetic relationships of the population of Bogotá, Colombia, was comparatively studied with regard to other populations from America, Europe, and Asia, by using the D1S80, VWA, and TH01 molecular loci. From a population history point of view, the population of Bogotá seems to be more related to a European origin, with several differential contributions coming from Amerindians rather than from African and Asian populations, when the D1S80 and TH01 markers were employed. However, the contribution was greater from African populations for the VWA marker. Several explanations are offered to resolve the genetic affiliation of this population. Am. J. Hum. Biol. 13:374–383, 2001. © 2001 Wiley‐Liss, Inc.     

HLA‐DQA1 and HLA‐DQB1 allele diversity and its extended haplotypes in Madeira Island (Portugal)

This study shows, for the first time, high‐resolution allele frequencies of HLA‐DQA1 loci in Madeira Island (Portugal) and allows us to better understand and refine present knowledge on DQB1 variation, with the identification of several alleles not previously reported in this population. Estimates on haplotype profile, involving HLA‐A, HLA‐B, HLA‐DRB1, HLA‐DQA1 and HLA‐DQB1, are also reported.     

HLA-DQA1 polymorphism in autochthonous Basques from Navarre (Spain): genetic position within European and Mediterranean scopes

In this work, a sample of 112 individuals from an autochthonous Basque population (Northern Navarre, Spain) were typed at the DNA level for the HLA-DQA1 locus, with the aim of characterizing its polymorphism and analyzing the genetic relationships of Basque Navarrese with other Caucasian populations. Northern Navarre is a neighboring area with Guipúzcoa, a province located in the core of the Basque territory having the highest proportion of Basque-speakers. In Navarrese population, the most frequent alleles were DQA1*01 (0.375) and DQA1*02 (0.259). Frequency clines for both DQA1*0103 allele and DQA1*04* allele cluster (including DQA1*0401, DQA1*0501 and DQA1*0601) among the European and Mediterranean populations considered are reported for the first time. Furthermore, a spatial structuring previously described for DQA1*02 allele is corroborated. The information provided by the highly polymorphic HLA-DQA1 locus was stressed by using genetic distances and non-metrical multidimensional scaling (MDS). The analysis of genetic relationships among populations showed a high genetic affinity between the Basque subpopulations of Northern Navarre and Guipúzcoa, which in turn tended to plot separately from the remaining European and Mediterranean populations. In the same way, the Basques showed no clear relationship to North African populations, as postulated in several previous HLA studies. The observed genetic heterogeneity seems to be conditioned by the high frequencies of the DQA1*02 allele in Basques from Guipúzcoa and North Navarre. These two subpopulations seem to show low levels of admixture with other non-Basque neighboring populations, probably because of their deeply rooted ethnicity and the existence of a linguistic barrier to random mating.     

Distribution of HLA Class II Alleles and Haplotypes in Mexican Mestizo Population: Comparison with Other Populations

We describe the analysis of the Major Histocompatibility Complex (MHC) class II polymorphism in Mexican Mestizo population. The study provides the HLA-DRB1, DQA1 and DQB1 allele frequencies in 99 Mexican Mestizos. DNA from these individuals was typed by PCR followed by hybridization using sequence specific oligonucleotides (PCR-SSO). The relationship with other worldwide populations was studied by using HLA data from 69 different populations and calculating neighbor-joining dendrograms and correspondence multidimensional values. The highest frequencies were for DRB1*0802 (allele frequency = 0.151), DRB1*0701 (allele frequency = 0.111) and DRB1*0407 (allele frequency = 0.106). Among the eight DQA1 alleles detected, the most frequent were DQA1*03011 (allele frequency = 0.257), DQA1*0501 (allele frequency = 0.227) and DQA1*0401 (allele frequency = 0.166). Twelve DQB1 alleles were found and four of them, DQB1*0302 (allele frequency = 0.237), DQB1*0301 (allele frequency = 0.176), DQB1*0201 (allele frequency = 0.166) and DQB1*0402 (allele frequency = 0.166) showed the highest frequencies. The haplotype DRB1*0802-DQA1*0401-DQB1*0402 (0.151) predominated clearly, followed by DRB1*0701-DQA1*0201-DQB1*0201 (0.111) and DRB1*0407-DQA1*03011-DQB1*0302 (0.101). Both genetic distances and correspondence analyses showed that Mexicans clustered with Amerindian population. These results suggest that the Mexican Mestizo population be principally characterized by haplotypes presents in Amerindian and Caucasian populations with a low frequency of Black haplotypes. In summary, the HLA class II haplotype frequencies demonstrated the tri-racial component existing in Mexican Mestizos.     

Polymorphism of HLA‐A, ‐B, ‐DRB1, ‐DQA1 and ‐DQB1 haplotypes in a Croatian population

We describe for the first time extended haplotypes in a Croatian population. The present study gives the HLA‐A, ‐B, ‐DRB1, ‐DQA1 and ‐DQB1 allele and haplotype frequencies in 105 families with at least two offspring. All individuals were studied by conventional serology for HLA class I antigens (A and B), while class II alleles (DRB1, DQA1, DQB1) were typed using the PCR–SSOP method. HLA genotyping was performed by segregation in all 105 families. For extended haplotype analysis, 420 independent parental haplotypes were included. Fourteen HLA‐A, 18 HLA‐B, 28 DRB1, 9 DQA1 and 11 DQB1 alleles were found in the studied population. Most of the DRB1 alleles in our population had an exclusive association with one specific DQA1‐DQB1 combination. This strong linkage disequilibrium within the HLA class II region is often extended to the HLA‐B locus. A total of 10 HLA‐A, ‐B, ‐DRB1, ‐DQA1, ‐DQB1 haplotypes were observed with a frequency ≤ 1.0%. The three most frequent haplotypes were HLA‐A1, B8, DRB1*0301, DQA1*0501, DQB1*0201; HLA‐A3, B7, DRB1*1501, DQA1*0102, DQB1*0602 and HLA‐A24, B44, DRB1*0701, DQA1*0201, DQB1*02. These results should provide a useful reference for further anthropological studies, transplantation studies, and studies of associations between HLA and diseases.     

Proceedings of the Society for the Study of Human Biology

This study reports the genetic variation at three variable number of tandem repeat (VNTR) loci (APOB, D17S5 and D1S80) in two tribes (Thoti and Kolam) of Andhra Pradesh, India. Kolams constitute 1% of the total scheduled tribal population of Andhra Pradesh, while Thoti is a numerically small tribe. All three genetic loci were genotyped using the polymerase chain reaction (PCR) technique and were polymorphic in both populations. At the D1S80 locus, both populations showed higher frequencies of allele *31 (9–14%) than other Indian populations. In the APOB system, Thoti showed a very high frequency of allele *37 (54%) and for D17S5 system allele *4 was the most common in Thoti (32%) and allele *2 in Kolam (28%). Both tribes differed statistically significantly from other tribal populations of the region. The level of gene differentiation was low (G_ST = 0.038) for Indian tribal populations. The allele frequency distribution, heterozygosity and genetic diversity analysis shows that the observed genetic variation is socially and geographically structured.     

Genetic variation and relationships at six VNTR loci in two distinct sample populations in Brazil

Background: The Brazilian population has been the focus of intensive genetic study due to admixture characteristics whereas there are few reports on the variability of VNTR loci in Brazil.

Primary objective: The aim of this study was to analyse genetic parameters in sample populations from two geographically distant regions: São Luís City, in Maranhão State and Campinas City, in São Paulo State. We investigated if distinct colonization influences could produce detectable differences in genetic background.

Subject and methods: DNA samples from peripheral drained blood were obtained from unrelated individuals who underwent paternity testing. Allelic variation in six VNTR loci (D2S44, D4S139, D5S110, D8S358, D10S28 and D17S79) was evaluated. The results were compared to reference databases available for general Latin-derived European and African–American populations as well as for other Brazilian groups.

Results: This study reveals that forensic population parameters did not show differences among regions, although we detected admixture values varying between the south-east and north-east of Brazil.

Conclusions: Differences between the two samples are probably due to different admixture proportions of European- and African-derived alleles in each region; both populations are in Hardy–Weinberg equilibrium. In addition, the allelic frequency for all loci, in both populations, can be used as database for forensic purposes.     

Human leucocyte antigens class II allele and haplotype association with Type 1 Diabetes in Madeira Island (Portugal)

This study confirms for Madeira Island (Portugal) population the Type 1 Diabetes (T1D) susceptible and protective Human leucocyte antigens (HLA) markers previously reported in other populations and adds some local specificities. Among the strongest T1D HLA associations, stands out, as susceptible, the alleles DRB1*04:05 (OR = 7.3), DQB1*03:02 (OR = 6.1) and DQA1*03:03 (OR = 4.5), as well as the haplotypes DRB1*04:05‐DQA1*03:03‐DQB1*03:02 (OR = 100.9) and DRB1*04:04‐DQA1*03:01‐DQB1*03:02 (OR = 22.1), and DQB1*06:02 (OR = 0.07) and DRB1*15:01‐DQA1*01:02‐DQB1*06:02 (OR = 0.04) as protective. HLA‐DQA1 positive for Arginine at position 52 (Arg52) (OR = 15.2) and HLA‐DQB1 negative for Aspartic acid at the position 57 (Asp57) (OR = 9.0) alleles appear to be important genetic markers for T1D susceptibility, with higher odds ratio values than any single allele and than most of the haplotypes. Genotypes generated by the association of markers Arg52 DQA1 positive and Asp57 DQB1 negative increase T1D susceptibility much more than one would expected by a simple additive effect of those markers separately (OR = 26.9). This study also confirms an increased risk for DRB1*04/DRB1*03 heterozygote genotypes (OR = 16.8) and also a DRB1*04‐DQA1*03:01‐DQB1*03:02 haplotype susceptibility dependent on the DRB1*04 allele (DRB1*04:01, OR = 7.9; DRB1*04:02, OR = 3.2; DRB1*04:04, OR = 22.1).     

Genetic variation observed at three tetrameric short tandem repeat loci HumTHO1, TPOX,and CSF1PO— in five ethnic population groups of northeastern India

This paper portrays the genetic variation observed at three tetrameric short tandem repeat (STR) loci HumTHO1, TPOX, and CSF1PO in five ethnic population groups from northeastern India. The study also specifies the suitability of use of these markers for forensic testing. The populations studied included three tribal groups (Kuki, Naga and Hmar), one Mongoloid caste group (Meitei), and a religious caste group (Manipuri Muslims). The loci were highly polymorphic in the populations, and all loci met Hardy–Weinberg expectations. No evidence for association of alleles among the loci was detected. The probability of match for the three loci of the most frequent genotype in the five population groups ranged between 2.6 × 10⁻⁴ and 6.6 × 10⁻⁵. The average heterozygosity among the population groups was approximately 70% with the overall extent of gene differentiation among the five groups being high (G_st = 0.046). Genetic affinity among the populations reveal very close association between the Kuki, Hmar, Naga, and Meitei. The Manipuri Muslims, despite being found in the same region, have had no admixture with these populations and maintain a substantial distance with the other groups. The genetic polymorphism data suggest that the studied systems can be used for human identity testing to estimate the frequency of a multiple locus STR DNA profile in population groups of northeastern India. Am. J. Hum. Biol. 13:23–29, 2001. © 2001 Wiley‐Liss, Inc.     

Multiple sclerosis: association to HLA DQalpha in a tropical population.

Studies performed in subtropical populations have found significant association between the phenotype multiple sclerosis (MS) and the major histocompatibility complex (MHC). We present the results of a case-control study conducted on a tropical population (Antioquia, Colombia) in order to detect a possible association between MS and HLA DQalpha (HLA DQA1*) alleles. Forty chromosomes belonging to MS patients were compared to two sets of controls (40 and 910 chromosomes, respectively). The HLA DQA1*0101 and DQA1*0102 alleles were found in a significantly higher proportion among the cases than among the controls, whereas the HLA DQA1*0103 allele was found in a significantly lower proportion of the cases. These results suggest that the association of HLA DQA1*0101, DQA1*0102 and DQA1*0103 to the MS phenotype found in Caucasian subtropical populations remains in individuals with MS inhabiting the tropics. This finding could mean that the major genetic component associated to the MHC in subtropical populations is the same in the tropics.