No abstract

Numerical chromosome abnormalities (aneuploidies) are among the most common known causes of mental retardation and the leading cause of pregnancy loss in humans. They primarily arise by the process of meiotic non-disjunction. We still know very little about the contribution of genetic and environmental causes for non-disjunction in humans. In order to increase our understanding of the epidemiology of human trisomies, it is necessary to establish the proportion of cases occurring in the first or second division of meiosis. Trisomic patients will display, in study of microsatellite typed by the polymerase chain reaction (PCR), three fragment peaks of equal intensity, two fragments at an average 2:1 dosage or one individual fragment. In this work we describe a statistical approach for estimation of the fraction of meiosis I non-disjunctions (F) in the absence of the parental information. First we determine a probability model for the number of peaks in a polymorphic microsatellite locus, which is a function of F. Based on this model, we obtain a maximum likelihood estimator for F, using the observed proportion of one, two and three allele patterns in trisomic individuals. Relying on the properties of maximum likelihood theory, we also calculate the asymptotic variance and confidence intervals for F. Owing to the fact that the samples of trisomic patients are limited in number, the use of asymptotic theory may be compromised. Thus, we employ the bootstrap technique to build confidence intervals for F and compare the results with those obtained from the normal theory. This estimator that dispenses the need to study parents opens the possibility of using archival material for comparative epidemiological studies of Down's syndrome and other aneuploidies. In this paper we propose a probability model to estimate the fraction of meiosis I non-disjunction, F, by only using the proportion of allele patterns of trisomy individuals, while traditional methods require typing pericentromeric markers from those affected and their parents.

BackgroundBrazilian Amerindians have experienced a drastic population decrease in the past 500 years. Indeed, many native groups from eastern Brazil have vanished. However, their mitochondrial mtDNA haplotypes, still persist in Brazilians, at least 50 million of whom carry Amerindian mitochondrial lineages. Our objective was to test whether, by analyzing extant rural populations from regions anciently occupied by specific Amerindian groups, we could identify potentially authentic mitochondrial lineages, a strategy we have named 'homopatric targeting'.ResultsWe studied 173 individuals from Queixadinha, a small village located in a territory previously occupied by the now extinct Botocudo Amerindian nation. Pedigree analysis revealed 74 unrelated matrilineages, which were screened for Amerindian mtDNA lineages by restriction fragment length polymorphism. A cosmopolitan control group was composed of 100 individuals from surrounding cities. All Amerindian lineages identified had their hypervariable segment HVSI sequenced, yielding 13 Amerindian haplotypes in Queixadinha, nine of which were not present in available databanks or in the literature. Among these haplotypes, there was a significant excess of haplogroup C (70%) and absence of haplogroup A lineages, which were the most common in the control group. The novelty of the haplotypes and the excess of the C haplogroup suggested that we might indeed have identified Botocudo lineages. To validate our strategy, we studied teeth extracted from 14 ancient skulls of Botocudo Amerindians from the collection of the National Museum of Rio de Janeiro. We recovered mtDNA sequences from all the teeth, identifying only six different haplotypes (a low haplotypic diversity of 0.8352 ± 0.0617), one of which was present among the lineages observed in the extant individuals studied.ConclusionsThese findings validate the technique of homopatric targeting as a useful new strategy to study the peopling and colonization of the New World, especially when direct analysis of genetic material is not possible.

We investigate the heritability of and pleiotropic relationships among triglycerides and cholesterol lipoproteins that have long been considered traditional risk factors for cardiovascular disease. Quantitative lipid and lipoprotein phenotypes were determined for a cross-sectional sample of a community in Jequitinhonha valley in northern Minas Gerais state, Brazil. The sample consisted primarily of subsistence farmers. Two hundred sixty-nine individuals (128 males and 141 females), ages 18-88 years, were sampled. Eighty-eight percent (n = 252) of the individuals belonged to a single pedigree, which was highly informative for genetic analysis. Data on anthropometrics, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, and triglycerides were available for each study participant. Extended pedigrees were constructed using the pedigree-based data management software PedSys. Univariate and bivariate variance-components analyses, adjusted by sex and age, were performed using the SOLAR software package. Heritability estimates of lipids and lipoproteins ranged from 29% to 45% (p < 0.008). The highest heritability estimated was for HDL-C (h2 = 44.8%, p < 0.0001), and this was the only trait that exhibited a significant household effect (c2 = 25%). Strong positive genetic correlations were found between triglycerides and very low density lipoprotein (VLDL) (rhog = 0.998) and between total cholesterol and LDL-C (rhog = 0.948). Significant genetic correlations were also found between triglycerides and LDL-C, between total cholesterol and VLDL, and between total cholesterol and LDL-C and VLDL, and finally between LDL and VLDL. There was a significant negative environmental correlation between triglycerides and HDL-C (rhoe = -0.406).