Terena Amerindian group autosomal STR data: comparison studies with other Brazilian populations.

Allele frequencies for the high polymorphic short tandem repeats (STR) loci PentaE, PentaD, D18S51, D21S11, TH01, D3S1358, FGA, D16S539, D7820, D13S317, vWA and D81179 were analysed in an native Amerindian population from Mato Grosso do Sul state named Terena. Deviations from Hardy-Weinberg expectations were evaluated and the results showed no differences from equilibrium in all loci. The combined power of discrimination and the combined power of exclusion for the 12 tested STR loci were 0.99999999 and 0.999999 respectively. The Terena population data were compared to other from 11 Brazilian populations (Amazônia, Pernambuco, Mato Grosso do Sul, São Paulo, Rio Grande do Sul, Alagoas, Sergipe, Rio Grande do Norte, Santa Catarina, Rondônia and Rio de Janeiro) representing the major Brazilian geographic regions. The F(ST) comparative analysis showed no significant differences between all those populations except when comparing Terena with the remained ones.

Beta3-adrenergic receptor polymorphism is related to cardiometabolic risk factors in obese Brazilian subjects.

We determined whether ADRbeta3 polymorphism is associated with obesity-related traits in 140 obese patients. Molecular analysis was performed by PCR and RFLP. Individuals carrying the Arg64 allele had a lower waist-to-hip ratio, higher adiponectin and high-density lipoprotein cholesterol levels, and a tendency towards lower blood pressure. In contrast, Trp64/Trp64 carriers were at greater risk for dysmetabolic phenotypes (odds ratio = 2.88, P = 0.03).

Analysis of renin-angiotensin-aldosterone system gene polymorphisms in resistant hypertension.

Essential hypertension is a disease multifactorially triggered by genetic and environmental factors. The contribution of genetic polymorphisms of the renin-angiotensin-aldosterone system and clinical risk factors to the development of resistant hypertension was evaluated in 90 hypertensive patients and in 115 normotensive controls living in Southwestern Brazil. Genotyping for insertion/deletion of angiotensin-converting enzyme, angiotensinogen M235T, angiotensin II type 1 receptor A1166C, aldosterone synthase C344T, and mineralocorticoid receptor A4582C polymorphisms was performed by PCR, with further restriction analysis when required. The influence of genetic polymorphisms on blood pressure variation was assessed by analysis of the odds ratio, while clinical risk factors were evaluated by logistic regression. Our analysis indicated that individuals who carry alleles 235-T, 1166-A, 344-T, or 4582-C had a significant risk of developing resistant hypertension (P < 0.05). Surprisingly, when we tested individuals who carried the presumed risk genotypes A1166C, C344T, and A4582C we found that these genotypes were not associated with resistant hypertension. However, a gradual increase in the risk to develop resistant hypertension was detected when the 235-MT and TT genotypes were combined with one, two or three of the supposedly more vulnerable genotypes - A1166C (AC/AA), C344T (TC/TT) and A4582C (AC/CC). Analysis of clinical parameters indicated that age, body mass index and gender contribute to blood pressure increase (P < 0.05). These results suggest that unfavorable genetic renin-angiotensin-aldosterone system patterns and clinical risk variables may contribute to increasing the risk for the development of resistant hypertension in a sample of the Brazilian population.

LEPR p.Q223R, beta3-AR p.W64R and LEP c.-2548G>A gene variants in obese Brazilian subjects.

Obesity is due to the combined effects of genes, environment, lifestyle, and the interactions of these factors. The adrenergic receptor beta3 (beta3-AR), leptin (LEP) and leptin receptor (LEPR) genes have been intensively evaluated in the search of variants that could be related to obesity and its cardiometabolic complications. The results of most of these studies have been controversial. In the present study, we investigated the relationship of the beta3-AR p.W64R, LEP c.-2548G>A and LEPR p.Q223R gene variants with body mass index (BMI), in Brazilian subjects of different genetic backgrounds and ethnic origins. Two hundred obese patients (60 males, 140 females, BMI > or = 30 kg/m2) were screened and compared to 150 lean healthy subjects (63 males, 87 females, BMI < or = 24 kg/m2). Genomic DNA was extracted and amplified by polymerase chain reaction. Polymerase chain reaction products were digested with specific restriction enzymes and separated by electrophoresis. There was no significant difference in the genotype frequency of the beta3-AR p.W64R and the LEP c.-2548G>A polymorphisms, between lean and obese subjects. However, the genotype and allele frequencies of the LEPR p.Q223R variant were significantly different between the normal weight and obese groups. Haplotype analysis has shown an association between the G/G allelic combination of c.-2548G>A LEP and c.668A>G LEPR, in obese subjects. Our results suggest that genetic variability in the leptin receptor is associated with body weight regulation, the LEPR p.Q223R variant being related to BMI increase. The haplotype combination of LEP c.-2548G>A and LEPR p.Q223R variants was related to a 58% increase in obesity risk.

Personalized diagnosis by cached solutions with hypertension as a study model.

Statistical modeling of links between genetic profiles with environmental and clinical data to aid in medical diagnosis is a challenge. Here, we present a computational approach for rapidly selecting important clinical data to assist in medical decisions based on personalized genetic profiles. What could take hours or days of computing is available on-the-fly, making this strategy feasible to implement as a routine without demanding great computing power. The key to rapidly obtaining an optimal/nearly optimal mathematical function that can evaluate the "disease stage" by combining information of genetic profiles with personal clinical data is done by querying a precomputed solution database. The database is previously generated by a new hybrid feature selection method that makes use of support vector machines, recursive feature elimination and random sub-space search. Here, to evaluate the method, data from polymorphisms in the renin-angiotensin-aldosterone system genes together with clinical data were obtained from patients with hypertension and control subjects. The disease "risk" was determined by classifying the patients' data with a support vector machine model based on the optimized feature; then measuring the Euclidean distance to the hyperplane decision function. Our results showed the association of renin-angiotensin-aldosterone system gene haplotypes with hypertension. The association of polymorphism patterns with different ethnic groups was also tracked by the feature selection process. A demonstration of this method is also available online on the project's web site.

Considerations on the effect of anti-sandfly antibodies on biological parameters of Lutzomyia longipalpis (Lutz & Neiva, 1912) (Diptera: Psychodidae: Phlebotominae).

The immunization of vertebrate hosts with vector components may be an alternative for the control of diseases transmitted by insects. In the present study we evaluated the effects of anti-sandfly antibodies on some of the biological parameters of female Lutzomyia longipalpis, a vector of visceral leishmaniasis. Rabbits were immunized with extracts of gut from blood-fed (GB) or sugar-fed (GS) females, carcass of sugar-fed (CS) or blood-fed (CB) females, and with repeated sandfly bites (BITE). Immune sera showed increased antibody titers compared to pre-immunized animals, and specific bands were detected by Western Blot. An analysis of biological parameters revealed a decline in fecundity in the group of females fed on rabbits immunized with GB and BITE. Longevity and mortality were studied in females with oviposition (parous) and without oviposition (nulliparous). Nulliparous females that fed on rabbits immunized with bites died in the highest percentage. A mortality analysis after egg laying revealed a peak on the fifth day in all the groups, but females fed on rabbit subjected to repeated bites showed a shift towards the third day.

Familial aggregation of Leishmania chagasi infection in northeastern Brazil.

A sample of 1,604 individuals belonging to 243 nuclear families from an endemic area of visceral leishmaniasis (Jacobina, Bahia State, Brazil) was studied to disclose the intrafamilial pattern of infection. Significant father to offspring, mother to offspring, and sibling to sibling associations, in contrast a with nonsignificant father to mother association, clearly indicate a familial aggregation of the infection, with a strong suggestion of at least partial genetic involvement.

Admixture and relationships of the population of Jacobina, Bahia, Brazil.

As part of the Cornell-Bahia project on leishmaniasis, the people of Jacobina in the state of Bahia in northeastern Brazil were studied for five genetic polymorphisms: ABO blood groups, hemoglobin variants, PGM1, 6PGD, and adenylate kinase. A maximum likelihood method of calculation of frequency of genes for these traits indicates that the ancestry of the people is 45% African, 43% Portuguese, and 12% Brazilian Indian. This estimate is similar to previous estimates of admixture in the people of northeastern Brazil, except for more African and less Caucasian ancestry. Previous distance relationships, based upon physical traits only, showed the population of Jacobina to be similar to Seminole Indians of Florida and equally distant from Whites and Blacks. While not strictly comparable, the genetic and morphologic pictures of relationships are compatible and show concordance with surnames. The presence of Hemoglobin C and the frequencies of alleles of PGM1 and 6PGD in the Jacobina population are consistent with the greater importation of Africans into Brazil from Costa de Mina on the Guinea Coast than from Angola. © 1996 Wiley-Liss, Inc.

Biological and biochemical characterization of isolates of Trypanosoma evansi from Pantanal of Matogrosso--Brazil.

Ten isolates of Trypanosoma evansi from the Pantanal region of Brazil, recently derived from coati (Nasua nasua, carnivora, Procyonidae), horses and dogs, were characterized on the basis of biological (experimental infections in Wistar rats) and biochemical (multilocus enzyme eletrophoresis) data. Biological data were analyzed by Nested analysis of variance and Kruskal-Wallis. Marked heterogeneity in virulence was observed in the isolates. Some of the isolates showed an undulating parasitaemia, typical for African trypanosomes. This biological heterogeneity did not correspond with the biochemical homogeneity observed in the T. evansi isolates. T. evansi has one of the widest distributions and greatest range of mammalian hosts and is widely recognized to have evolved from Trypanosoma brucei. Adaptability of T. evansi was not reflected in the variability of biochemical and molecular parameters studied to date. The variability in virulence was very significant, but not correlated with the host from which it was derived. These data suggested that, in the region studied, T. evansi is transmitted among both domestic and sylvatic animals in one single transmission cycle.

Mosquito population dynamic (Diptera: Culicidae) in a eutrophised dam.

This study observed the mosquito population in a rural eutrophised dam. Larvae of L3 and L4 stages and pupae were dipped out during twelve month collections and the reared to the adult stage for identification. The collections were done along nine metres from the edge of the dam divided in three parts (P1, P2 and P3), each part being 3 m long. P1 did not have vegetation (grass) along its edge,which would reach or sink into the water to promote some shade on the marginal water. A total of 217 adults of four species was identified with the following constancies and frequencies: Culex quinquefasciatus (Say, 1823) (83% and 40.6%), Anopheles (Nyssorhynchus) evansae (Brèthes, 1926) (92% and 26.7%), Anopheles (Nyssorhynchus) rangeli (Gabaldon, Cova Garcia and Lopez, 1940) (83% and 14.3%) and Culex nigripalpus (Theobald, 1901) (33% and 18.4%). C. quinquefasciatus, A. evansae, A. rangeli and C. nigripalpus were more frequent in the quarters Nov./Dec./Jan. (85.7%), May/June/July (75%), Aug./Sept./Oct. (29.4%) and Aug./Sept./Oct. (23.5%) particularly in the months of December (88.4%) Sept.tember (48.94), (38.3) and August (47.62) respectively. The presence of C. quinquefasciatus and the high incidence of Daphinia sp. and also the levels of Organic Nitrogen (0.28 mg/L) and of total Phosphorus (0.02 mg/L) are indications of the eutrophication of the dam. There was a difference regarding the total of Anopheles (A. avansae + A. rangeli) and Culex species (C. quinquefasciatus + C. nigripalpis) between P1 and P2 (χ(2) = 0.0097), P1 and P3 (χ(2) = 0.0005), but not between P2 and P3 (χ(2) = 0.2045).The high C. quinquefasciatus constancy and frequency were confirmed to be a good biological indicator for a eutrophised environment and A. evansae showed a good potential for this environment. Vegetation can be an important factor for anopheline population dynamic also in eutrophic breeding sites.

[Some demographic aspects of a rural northeast Brazilian population]. / Alguns aspectos demograficos de uma populacao rural do Nordeste brasileiro.

"A sample of 1,806 families from the Brazilian Northeastern region was analysed in order to study the effect of several socio-economical parameters upon the reproductive structure of this population." The data are from a hospital in Sao Paulo district and were collected in 1969-1970. The results show the low health status of the population as a whole, which in turn, has an influence on mortality. In particular, postnatal mortality rates are shown to increase from the south to the north of the region, in association with different levels of socioeconomic development. (SUMMARY IN ENG)

Note on estimates of the inbreeding coefficient through study of pedigrees and isonymous marriages.

Crow and Mange (1965) developed a method to estimate the inbreeding coefficient (F) through an ingenious surname analysis. Such formulations assume a regularity of transmission of surnames, monophyletism, and random occurrence of consanguineous marriages. Accordingly, the ratio of isonymous partners to F of the offspring is equal to 4. Nevertheless, genealogy analyses show that the consanguineous marriages do not necessarily occur regularly. Therefore the isonymy analysis gives a misestimation of the inbreeding coefficient, depending on the prevailing form of nonrandomness. We suggest a small correction to the formulation in situations when pedigree information is available. The weighted mean of the ratio of isonymous partners to F of the known consanguineous marriages is suggested as a way to improve the formulas. The technique was applied to a northeastern Brazilian sample, and the results agree well with those of bioassays and therefore provide an apparently more realistic estimate of the inbreeding coefficient by isonymy.

Is there a sex-phenotype association for esterase D (EC 3.1.1.1)?

Recently, a significant sex distortion of the esterase D locus segregation, both in Portugal and Germany, was reported. In contrast to these puzzling results, data on around 1,200 informative northeastern Brazilian individuals did not show any signs of a sex-phenotype association (chi 2 = 0.35). The joint analysis of this sample together with that of the previous report showed that, although the pooled material presented a significant sex distortion (p less than 0.05), the heterogeneity was also high (p less than 0.05) as to discourage any generalization based upon the European findings. Moreover, since the present sample is almost 3 times larger than the pooled European one, the whole picture suggests strongly that there is no segregation distortion attributed to sex, at this locus.

Causal analysis of the variability of IgA, IgG, and IgM immunoglobulin levels.

The interindividual variability of IgA, IgG, and IgM immunoglobulin levels was studied using path analysis in a northeastern Brazilian sample (nuclear families) to determine the genetic and/or environmental causes of their variation. The path analysis model decomposes the phenotype into genetic causes (autosomal and X-chromosome-linked genes) and environmental causes. A significant familial aggregation, mainly resulting from autosomal components, was detected for the 3 immunoglobulin levels. The values of genetic heritability were h2 = 0.410 +/- 0.030 for IgA, h2 = 0.617 +/- 0.020 for IgG, and h2 = 0.540 +/- 0.023 for IgM, and the values for environmental-cultural heritability were c2 = 0.085 +/- 0.034 for IgA, c2 = 0.084 +/- 0.027 for IgG, and c2 = 0.023 + 0.023 for IgM. Our results did not show a heritable component resulting from X-chromosome-linked genes on IgM levels, as suggested by some studies (Wood et al. 1969; Grundbacher 1972; Purtilo and Sullivan 1979). Some additional results were that (1) age and IgA concentration were positively correlated, with IgA level increasing gradually from childhood to adulthood (p < 0.001); (2) sex and the age X sex interaction act on IgG concentration (p < 0.01); (3) age and IgM concentration are correlated (with children presenting lower levels than adults, especially in males, p < 0.01); and (4) a significant association exists between sex and IgM level (with females presenting higher levels than males, p < 0.001).

Heritability of quantitative orbital traits.

We conducted a study of 63 couples and their 242 normal children from northeastern Brazil (no facial malformations or deformities) to evaluate the heritability of 4 quantitative traits of the orbital region adjusted by covariance for sex, age, (age)2, sex x age, and sex x (age)2. The heritability is estimated as 0.514 for the mean horizontal diameter of the palpebral fissures, 0.454 for the interpupillary distance, 0.390 for the internal intercanthal distance, and 0.337 for the external intercanthal distance. The heritability of the first principal component of the orbital region is estimated as 0.418.

On the association between HLA-A1 and B5 and clinical forms of schistosomiasis mansoni.

The association between both HLA-A1 and B5 antigens and chronic forms of human schistosomiasis was studied in 64 patients and 26 normal controls from a southern Brazilian hospital. No apparent correlation between the chronic forms of the disease and the expression of those antigens was detected. However, the analysis of these data together with those observed on an Egyptian sample suggests that the presence of either of the antigens and the hepatomegalic forms of schistosomiasis is significant, without heterogeneity. Conversely, the association of histocompatibility antigens with splenomegaly is consistent and significant only for HLA-B5, but not HLA-A1.

Association between the acid phosphatase 1 and adenosine deaminase systems in a Brazilian sample.

Analyses of pairwise associations between several erythrocyte genetic systems were performed on a sample from a Brazilian trihybrid population. The present paper confirms the association between the ACP1 and ADA loci, the acid phosphatase 1 and adenosine deaminase systems. The results indicate that both selection and racial admixture may influence this association.

Acute Chagas' disease: plasma levels of alpha-2-macroglobulin and C-reactive protein in children under 13 years in a high endemic area of Bolivia.

We measured the levels of two human acute phase proteins (APP), alpha-2-macroglobulin (A2M) and C-reactive protein (CRP), in sera of 56 healthy and 84 acute chagasic children aged from 1 to 13 years old, from a highly endemic area in Bolivia. In such areas, children are continuously exposed to vectors and the frequency of acute cases increases with age. Quantitation of A2M and CRP were performed using sandwich ELISAs, that were shown to be sensitive, reproducible and suited for studying many samples rapidly. A2M levels observed were higher in healthy younger children, decreasing with age until children reached their teens, and their distribution suggested a relationship between A2M concentration and age that could be consistently expressed by a power function. The same does not occur with CRP levels. Concentrations of A2M were age-adjusted to allow comparison using sera collected from children with different ages. Both A2M and CRP were significantly increased in acute chagasic children. Since parasites are commonly present in blood and tissues during the acute phase of Chagas' disease, it is possible that the high levels of A2M may act as inhibitors of a high load of proteinases, derived either from the parasites, from host cell damage or from both.

Studies on populations of Lutzomyia longipalpis (Lutz & Neiva, 1912) (Diptera: Psychodidae: Phlebotominae) in Brazil.

Studies were performed on five Brazilian populations of Lutzomyia longipalpis: Salvaterra (PA), São José do Ribamar (MA), Canindé (CE), Natal (RN) and Gruta da Lapinha, Lagoa Santa (MG). No morphological differences were observed that could distinguish between these populations. Homogeneity tests showed that the allopatric populations display a certain heterogeneity and that the sympatric populations, with different patterns of spots, are homogeneous. The Student-Newman-Keuls test, represented by Euler-Venn diagrams, showed a disjunction between the populations from the north/northeast and the one from Gruta da Lapinha. Genetic distances between the four populations (excluding the Canindé population) were within the range of intrapopulational differences. The Gruta da Lapinha population displayed a heterozygotic deficiency that could be a consequence of high levels of inbreeding due to cryptic habits of living in a small cave. These results do not favor the hypothesis of a L. longipalpis species complex in Brazil, and the species should be considered high polymorphic.