Cláudia Emília Vieira Wiezel

Genomic ancestry in urban Afro-Brazilians

Brazil is the result of interethnic crosses of European, African and Amerindian populations. Allelic frequencies for seven STR loci (TH01, TPOx, CSF1PO, vWA, FES/FPS, F13A1 and CD4), obtained from a sample of 70 individuals identified as Afro-Brazilian and 150 as mulatto, are presented here. Based on the frequencies of these genetic markers, estimates of interethnic admixture showed 62%, 26% and 12% of European, African and Amerindian contribution, respectively, for the mulatto sample and 37% and 63% of European and African contribution, respectively, for the Afro-Brazilian sample.

European Ancestry Predominates in Neuromyelitis Optica and Multiple Sclerosis Patients from Brazil

Background Neuromyelitis optica (NMO) is considered relatively more common in non-Whites, whereas multiple sclerosis (MS) presents a high prevalence rate, particularly in Whites from Western countries populations. However, no study has used ancestry informative markers (AIMs) to estimate the genetic ancestry contribution to NMO patients. Methods Twelve AIMs were selected based on the large allele frequency differences among European, African, and Amerindian populations, in order to investigate the genetic contribution of each ancestral group in 236 patients with MS and NMO, diagnosed using the McDonald and Wingerchuck criteria, respectively. All 128 MS patients were recruited at the Faculty of Medicine of Ribeirão Preto (MS-RP), Southeastern Brazil, as well as 108 healthy bone marrow donors considered as healthy controls. A total of 108 NMO patients were recruited from five Neurology centers from different Brazilian regions, including Ribeirão Preto (NMO-RP). Principal Findings European ancestry contribution was higher in MS-RP than in NMO-RP (78.5% vs. 68.7%) patients. In contrast, African ancestry estimates were higher in NMO-RP than in MS-RP (20.5% vs. 12.5%) patients. Moreover, principal component analyses showed that groups of NMO patients from different Brazilian regions were clustered close to the European ancestral population. Conclusions Our findings demonstrate that European genetic contribution predominates in NMO and MS patients from Brazil.

Afro-derived Brazilian populations: male genetic constitution estimated by Y-chromosomes STRs and AluYAP element polymorphisms.

The genetic constitution of Afro‐derived Brazilian populations is barely studied. To improve that knowledge, we investigated the AluYAP element and five Y‐chromosome STRs (DYS19, DYS390, DYS391, DYS392, and DYS393) to estimate ethnic male contribution in the constitution of four Brazilian quilombos remnants: Mocambo, Rio das Rãs, Kalunga, and Riacho de Sacutiaba. Results indicated significant differences among communities, corroborating historical information about the Brazilian settlement. We concluded that besides African contribution, there was a great European participation in the constitution of these four populations and that observed haplotype variability could be explained by gene flow to quilombos remnants and mutational events in microsatellites (STRs). Am. J. Hum. Biol., 2009.

Analysis of five polymorphic DNA markers for indirect genetic diagnosis of haemophilia A in the Brazilian population

Summary.  Hemophilia A is an X‐linked, inherited, bleeding disorder caused by the partial or total inactivity of the coagulation factor VIII (FVIII). Due to difficulties in the direct recognition of the disease‐associated mutation in the F8 gene, indirect diagnosis using polymorphic markers located inside or close to the gene is used as an alternative for determining the segregation of the mutant gene within families and thus for detecting carrier individuals and/or assisting in prenatal diagnosis. This study characterizes the allelic and haplotype frequencies, genetic diversity, population differentiation and linkage disequilibrium of five microsatellites (F8Int1, F8Int13, F8Int22, F8Int25.3 and IKBKG) in samples of healthy individuals from São Paulo, Rio Grande do Sul and Pernambuco and of patients from São Paulo with haemophilia A to determine the degree of informativeness of these microsatellites for diagnostic purposes. The interpopulational diversity parameters highlight the differences among the analyzed population samples. Regional differences in allelic frequencies must be taken into account when conducting indirect diagnosis of haemophilia A. With the exception of IKBKG, all of the microsatellites presented high heterozygosity levels. Using the markers described, diagnosis was possible in 10 of 11 families. The F8Int22, F8Int1, F8Int13, F8Int25.3 and IKBKG microsatellites were informative in seven, six, five and two of the cases, respectively, demonstrating the effectiveness of using these microsatellites in prenatal diagnosis and in carrier identification in the Brazilian population.

A Statistical Study of the Association of Seven Dental Anomalies in the Brazilian Population

El objetivo de este estudio fue mostrar los patrones asociacion entre siete tipos de anomalias dentales (agenesia del segundo premolar, incisivo lateral superior en tamano reducido, infra-oclesis del primer molar inferior, hipoplasia del esmalte, erupcion ectopica del primer molar, dientes supernumerarios y erupcion ectopica de caninos superiores) en una muestra de poblacion sin tratamiento dental, de edades comprendidas entre los 7 a 14 anos. Un total de 172 pacientes fueron atendidos y se les realizo el examen clinico en la Clinica Infantil da Fundacion Educacional de Barretos. Once pacientes de el total fueron seleccionados de acuerdo con un primer diagnostico de anomalias dentales y presentado en la radiografia panoramica. Se observo una asociacion significativa (p <0,05) entre los seis pares de anomalias (agenesia de segundo premolar x erupcion ectopica del primer molar; agenesia del segundo premolar x infra-oclesis del primer molar inferior; agenesia del segundo premolar x incisivo lateral superior en tamano reducido; dientes supernumerarios x incisivo lateral superior en tamano reducido; erupcion ectopica del primer molar x hipoplasia de esmalte; infra-oclesis del primer molar inferior x incisivo lateral superior en tamano reducido), sugiriendo un origen genetico comun para estas condiciones. La asociacion no fue significativa en un solo caso donde hubo anomalias compartidas por los pacientes. La existencia de una anomalia es clinicamente relevante para el diagnostico precoz de una posible asociacion y una anomalia puede indicar un mayor riesgo de otras anomalias

Y-STR diversity and ethnic admixture in White and Mulatto Brazilian population samples

We investigated 50 Mulatto and 120 White Brazilians for the Y-chromosome short tandem repeat (Y-STR) markers (DYS19, DYS390, DYS391, DYS392 and DYS393) and found 79 different haplotypes in the White and 35 in the Mulatto sample. Admixture estimates based on allele frequencies showed that the admixture of the white sample was 89% European, 6% African and 5% Amerindian while the Mulatto sample was 93% European and 7% African. Results were consistent with historical records of the directional mating between European males and Amerindian or African females.

Y-Linked microsatellites in Amazonian Amerindians applied to ancestry estimates in Brazilian Afro-derived populations

Proper ancestral populations are required to determine accurate ancestry estimates for Afro‐derived Brazilian populations. Herein, we have genotyped Y‐STRs in Amazonian Amerindians to determine the ancestral contribution in quilombo remnant communities.

The SCA1 (Spinocerebellar ataxia type 1) and MJD (Machado-Joseph disease) CAG repeats in normal individuals: segregation analysis and allele frequencies

Spinocerebellar ataxia type 1 (SCA1) and Machado-Joseph disease (MJD/SCA3) are autosomal dominant neurodegenerative diseases caused by expansions of a CAG trinucleotide repeat in the SCA1 and MJD genes. These expanded sequences are unstable upon transmission, leading to an intergeneration increase in the number of repeats (dynamic mutation). The transmission of the CAG repeat was studied in normal mother-father-child trios, referred for paternity testing (SCA1, n = 367; MJD, n = 879). No segregation distortion was detected. The CAG allele frequencies were determined in 330 unrelated individuals (fathers from couples tested for paternity). The allele frequency distributions did not differ from those previously reported for European populations. The estimated values for the statistic parameters indicating diversity at the SCA1 locus did not differ much from those reported previously for other STRs in the Brazilian population, while those for the MJD locus were close to or higher than the maximum values of previous reports. This shows that SCA1 and MJD are highly informative loci for applications in genetic and population studies and for forensic analysis.

Haplotypes from the SLC45A2 gene are associated with the presence of freckles and eye, hair and skin pigmentation in Brazil

The Solute Carrier Family 45, Member 2 (SLC45A2) gene encodes the Membrane-Associated Transporter Protein (MATP), which mediates melanin synthesis by tyrosinase trafficking and proton transportation to melanosomes. At least two SLC45A2 coding SNPs [E272K (rs26722) and L374F (rs16891982)] were reported influencing normal variation of human pigmentation. Here we aimed at evaluating the influence of haplotypes of 12 SNPs within SLC45A2 in the determination of eye, hair and skin pigmentation in a highly admixed population sample and comparing their frequencies with the ones found in data retrieved from the 1000 Genomes Project. To achieve this goal, 12 SLC45A2 SNPs were evaluated in 288 unrelated individuals from the Ribeirão Preto city area, Southeastern Brazil. SNPs were genotyped by PCR-RFLP or Allele-specific PCR, followed by polyacrylamide gel electrophoresis. Haplotypes of each individual were inferred by two independent computational methods, PHASE and Partition-Ligation-Expectation-Maximization (PL-EM) algorithms, and 34 different haplotypes were identified. The hp9 haplotype was the most frequent (58.3%) and was associated with the presence of blond/red hair, pale skin, blue eyes and freckles. All haplotypes significantly associated with dark or light pigmentation features harbor the 374L and 374F alleles, respectively. These results emphasize the role played by haplotypes at SLC45A2 in the determination of pigmentation aspects of human populations and reinforce the relevance of SNP L374F in human pigmentation.