Revisiting the genetic ancestry of Brazilians using autosomal AIM-Indels.

There are many different studies that contribute to the global picture of the ethnic heterogeneity in Brazilian populations. These studies use different types of genetic markers and are focused on the comparison of populations at different levels. In some of them, each geographical region is treated as a single homogeneous population, whereas other studies create different subdivisions: political (e.g., pooling populations by State), demographic (e.g., urban and rural), or ethnic (e.g., culture, self-declaration, or skin colour). In this study, we performed an enhanced reassessment of the genetic ancestry of ~ 1,300 Brazilians characterised for 46 autosomal Ancestry Informative Markers (AIMs). In addition, 798 individuals from twelve Brazilian populations representing the five geographical macro-regions of Brazil were newly genotyped, including a Native American community and a rural Amazonian community. Following an increasing North to South gradient, European ancestry was the most prevalent in all urban populations (with values up to 74%). The populations in the North consisted of a significant proportion of Native American ancestry that was about two times higher than the African contribution. Conversely, in the Northeast, Center-West and Southeast, African ancestry was the second most prevalent. At an intrapopulation level, all urban populations were highly admixed, and most of the variation in ancestry proportions was observed between individuals within each population rather than among population. Nevertheless, individuals with a high proportion of Native American ancestry are only found in the samples from Terena and Santa Isabel. Our results allowed us to further refine the genetic landscape of Brazilians while establishing the basis for the effective application of an autosomal AIM panel in forensic casework and clinical association studies within the highly admixed Brazilian populations.

Histological profile and age at diagnosis of breast and ovarian tumors: A register-based study in Espirito Santo, Brazil.

Breast and ovarian cancers are important public health problems in Brazil. However, in various locations in the Brazilian territory these types of cancer remain poorly characterized. Therefore, this study aimed to compare data collected from the Pathology Services of two Oncology Reference Hospitals in Espirito Santo state (Brazil) with the data in previous Brazilian studies. Histological type frequency and age at diagnosis of breast and ovarian tumors between 2001-2004 and 2009-2010 were analyzed. Tumor size, histological grade, lymph node status, hormone receptor status [estrogen (ER) and progesterone receptors (PR)] as well as HER2 and Ki-67 marker status were obtained for the cases of infiltrating ductal carcinomas of the breast during the period 2009-2010. Categorical variables were described by their absolute and/or relative frequencies, while quantitative variables were expressed as the mean ± standard deviation and median, using 95% confidence intervals. Chi-square tests were performed to examine whether or not the studied variables differed by age at the time of diagnosis. Malignant breast tumors (1,758) and 119 malignant ovarian tumors were examined. Mean ages for malignant breast and ovarian tumors were 53.59 and 52.98 years, respectively. An increased tumor frequency in the age group of ≤35 years was observed for other malignant tumors of the breast during the period of 2009-2010, compared to 2001-2004. When considering only infiltrating ductal carcinomas with immunohistochemistry records available, there were 82.1% (133 cases) of ER+/PR+ tumors, 1.9% (3 cases) of ER-/PR-/HER2 3+ and 16.04% (26 cases) of ER-/PR-/HER2- tumors. The findings of this study demonstrated detailed information concerning breast and ovarian tumor behavior in the Espirito Santo state (Brazil), allowing for a precise comparison with other populations (Brazilian or international), which may be helpful in the planning of prevention and treatment strategies.

Analysis of genome instability in breast cancer.

Breast cancer is a heterogeneous disease, previously associated with genomic instability. Our aim was to analyze microsatellite markers in order to determine patterns and levels of instability, as well as possible correlations with histopathological parameters. Polymerase chain reaction was used to characterize microsatellite instability (MSI) and loss of heterozygosity (LOH) in 107 breast carcinomas at twelve microsatellite loci. Some of the markers were selected because of their relation to steroid hormone metabolism, which seems to be related to sporadic breast cancer risk. D5S346 and D17S250 markers showed a statistically significant frequency of MSI. LOH in D3S1611, D17S250, AR and ER-ß were associated with some parameters of worse prognosis. Marker group analysis showed that CYP19, AR and ER-ß were related to histological grade III, ER-negative and PR-negative cases. Our results suggest that marker group analysis may be preferred to the single marker strategy, being predictive of worst prognosis when single markers are unable to provide such information. A further evaluation of steroid metabolism genes and their association with low penetrance genes in breast cancer may be useful.

Polymorphism analysis of MTHFR, factor II, and factor V genes in the Pomeranian population of Espirito Santo, Brazil.

Pomeranian populations worldwide immigrated originally from the north of Europe, and because of their preferential marriage, religion, and cultural habits, they show little or no reproductive mixing with local populations. Methylenetetrahydrofolate reductase gene (MTHFR) C677T, Factor V Leiden, and Factor II G20210A polymorphisms are linked to augmented clotting and their frequencies may vary according to population ethnicity. We aimed to assess the frequencies of these thrombophilic alleles in the Pomeranian population residing in Espirito Santo and compare with the general population of the Espirito Santo state, Brazil. A total of 200 individuals were analyzed. The intrapopulation fixation index of the MTHFR C677T polymorphism was 0.03736. The observed heterozygosity was 0.44 and 0.4 for the general and Pomeranian populations, respectively. According to the chi-square test, both populations are in Hardy-Weinberg equilibrium. Four polymorphic alleles were detected for Factor II (2.02%) and 8 for Factor V (4.81%). Our results show that there is gene flow between the general and the Pomeranian population of Espirito Santo, which should no longer be considered an isolated population.

Genetic diversity and statistical parameters of 15 autosomal STR loci in the Pomeranian subpopulation of Espirito Santo State, Brazil.

Allelic frequencies and other population data analysis are reported for the 15 autosomal Short Tandem Repeats (STR) loci included in the PowerPlex(®)16 kit (CSF1PO, D13S317, D16S539, D18S51, D21S11, D3S1358, D5S818, D7S820, D8S1179, FGA, Penta D, Penta E, TPOX, TH01 and vWA) in Pomeranian's descendants from the Espirito Santo State (ES), Brazil, third largest population of Pomeranian's descendants in the world. They chose the mountain region of the state for their preferred geographic location, and they have a very peculiar lifestyle with a selective mating behavior which has maintained their characteristics as a relatively pure subpopulation. Blood samples were obtained from 82 unrelated volunteers from 11 different cities of Espirito Santo State, where there are the Pomeranian's descendants. All 15 loci analyzed showed Power of Discrimination (PD) values > 0.75. Except the TPOX locus, all analyzed loci were at Hardy-Weinberg equilibrium. This subpopulation has not yet been characterized for STR allelic frequencies used for forensic and genetic identification studies.

Molecular analysis of spinocerebellar ataxia trinucleotide repeat behavior in normal individuals of a Brazilian population.

There is a current lack of molecular studies analyzing the behavior of trinucleotide repeat expansions causative of Late Onset Spinocerebellar Ataxias in the Brazilian population. Therefore, this manuscript analyses normal families, as well as one hundred normal individuals of the Espirito Santo State to determine the trinucleotide repeat behavior and the allelic frequencies found in this population. The analysis of normal families demonstrated that, instead of being always stably transmitted over generations, expansions can occur between two generations of unaffected individuals, possibly contributing for the appearance of the ataxic phenotype. Allelic frequency studies demonstrated that some alleles are prevalent in the population, namely, allele 32 for the ATXN1 locus (21.5%); allele 21 for the ATXN2 locus (50%); allele 21 and 23 for the ATXN3 locus (14% each); allele 12 for the ATXN6 locus (21%) and allele 10 for the ATXN7 locus (22.5%).