Linguistic heterogeneity in Williams syndrome

Williams syndrome (WS) is a rare genetic disorder resulting from a deletion on chromosome 7. A number of studies have shown that individuals with WS have a superior linguistic profile compared to their non-verbal abilities, however the evidence has been inconclusive, as many studies have disputed such a profile. The vast majority of studies on WS have assumed a single, homogeneous WS linguistic profile in order to support various theoretical viewpoints. The present study investigated the linguistic profiles of 5 individuals with WS on a number of standardized verbal measures and in conversational settings. The results indicated substantially variable performance in all aspects of the verbal domain, which supports the view that WS, linguistically, is a rather heterogeneous condition and this should be taken into consideration when referring to it in theoretical accounts of language acquisition and debates on modularity.

Postprandial lipemia and cardiovascular disease risk: interrelationships between dietary, physiological and genetic determinants

Although the independence of the association and causality has not been fully established, non-fasting (postprandial) triglyceride (TG) concentrations have emerged as a clinically significant cardiovascular disease (CVD) risk factor. In the current review, findings from three insightful prospective studies in the area, namely the Women's Health Study, the Copenhagen City Heart Study and the Norwegian Counties Study, are discussed. An overview is provided as to the likely etiological basis for the association between postprandial TG and CVD, with a focus on both lipid and non-lipid (inflammation, hemostasis and vascular function) risk factors. The impact of various lifestyle and physiological determinants are considered, in particular genetic variation and meal fat composition. Furthermore, although data is limited some information is provided as to the relative and interactive impact of a number of modulators of lipemia. It is evident that relative to age, gender and body mass index (known modulators of postprandial lipemia), the contribution of identified gene variants to the heterogeneity observed in the postprandial response is likely to be relatively small. Finally, we highlight the need for the development of a standardised ‘fat tolerance test’ for use in clinical trials, to allow the integration and comparison of data from individual studies

Prevalence of GJB2 (Connexin-26) and GJB6 (Connexin-30) Mutations in a Cohort of 300 Brazilian Hearing-Impaired Individuals: Implications for Diagnosis and Genetic Counseling

Objective: Hereditary nonsyndromic deafness is an autosomal recessive condition in about 80% of cases, and point mutations in the GJB2 gene (connexin 26) and two deletions in the GJB6 gene (connexin 30), del(GJB6-D13S1830) and del(GJB6-D13S1854), are reported to account for 50% of recessive deafness, Aiming at establishing the frequencies of GJB2 mutations and GJB6 deletions in the Brazilian population, we screened 300 unrelated individuals with hearing impairment, who were not affected by known deafness related syndromes. Methods: We firstly screened the most frequently reported mutations, c.35delG and c.167delT in the GJB2 gene, and del(GJB6-D13S1830) and del(GJB6-D13S1854) in the GJB6 gene, through specific techniques. The detected c.35delG and c.167delT mutations were validated by sequencing. Other mutations in the GJB2 gene were screened by single-strand conformation polymorphism and the coding region was sequenced when abnormal patterns were found. Results: Pathogenic mutations in GJB2 and GJB6 genes were detected in 41 individuals (13.7%), and 80.5% (33/41) presented these mutations in homozygosis or compound heterozygosis, thus explaining their hearing defect. The c.35delG in the GJB2 gene was the most frequent mutation (37/300; 12.4%), detected in 23% familial and 6.2% the sporadic cases. The second most frequent mutation (1%; 3/300) was the del(GJB6- D13S1830), always found associated with the c.35delG mutation. Nineteen different sequence variations were found in the GJB2 gene. In addition to the c.35delG mutation, nine known pathogenic alterations were detected 0 67delT, p.Trp24X, p.Val37lle, c.176_191del16, c.235delC, p.Leu90Pro, p.Arg127His, c.509insA, and p.Arg184Pro, Five substitutions had been previously considered benign polymorphisms: c.-15C>T, p.Val27lle, p.Met34hr, p.Ala40Ala, and p.Gly160Ser. Two previously reported Mutations of unknown pathogenicity were found (p.Lys168Arg, and c.684C>A), and two novel substitutions, p.Leu81Val (c.G241C) and p.Met195Val (c.A583G), both in heterozygosis without an accompanying mutation in the other allele. None of these latter four variants of undefined status was present in a sample of 100 hearing controls. Conclusions: The present study demonstrates that Mutations in the GJB2 gene and del(GJB6 D13S1830) are important causes of hearing impairment in Brazil, thus justifying their screening in a routine basis. The diversity of variants in our sample reflects the ethnic heterogeneity of the Brazilian population.

Analysis of the genome of Spodoptera frugiperda nucleopolyhedrovirus (SfMNPV-19) and of the high genomic heterogeneity in group II nucleopolyhedroviruses

The genome of the most virulent among 22 Brazilian geographical isolates of Spodoptera frugiperda nucleopolyhedrovirus, isolate 19 (SfMNPV-1 9), was completely sequenced and shown to comprise 132 565 bp and 141 open reading frames (ORFs). A total of 11 ORFs with no homology to genes in the GenBank database were found. Of those, four had typical baculovirus; promoter motifs and polyadenylation sites. Computer-simulated restriction enzyme cleavage patterns of SfMNPV-1 9 were compared with published physical maps of other SfMNPV isolates. Differences were observed in terms of the restriction profiles and genome size. Comparison of SfMNPV-1 9 with the sequence of the SfMNPV isolate 3AP2 indicated that they differed due to a 1427 bp deletion, as well as by a series of smaller deletions and point mutations. The majority of genes of SfMNPV-1 9 were conserved in the closely related Spodoptera exigua NPV (SeMNPV) and Agrotis segetum NPV (AgseMNPV-A), but a few regions experienced major changes and rearrangements. Synthenic maps for the genomes of group 11 NPVs revealed that gene collinearity was observed only within certain clusters. Analysis of the dynamics of gene gain and loss along the phylogenetic tree of the NPVs showed that group 11 had only five defining genes and supported the hypothesis that these viruses form ten highly divergent ancient lineages. Crucially, more than 60% of the gene gain events followed a power-law relation to genetic distance among baculoviruses, indicative of temporal organization in the gene accretion process.

Trypanosoma cruzi maxicircle heterogeneity in Chagas disease patients from Brazil

The majority of individuals in the chronic phase of Chagas disease are asymptomatic (indeterminate form, IF). Each year, similar to 3% of them develop lesions in the heart or gastrointestinal tract. Cardiomyopathy (CCHD) is the most severe manifestation of Chagas disease. The factors that determine the outcome of the infection are unknown, but certainly depend on complex interactions amongst the genetic make-up of the parasite, the host immunogenetic background and environment. In a previous study we verified that the maxicircle gene NADH dehydrogenase (mitochondrial complex 1) subunit 7 (ND7) from IF isolates had a 455 bp deletion compared with the wild type (WT) ND7 gene from CCHD strains. We proposed that ND7 could constitute a valuable target for PCR assays in the differential diagnosis of the infective strain. In the present study we evaluated this hypothesis by examination of ND7 structure in parasites from 75 patients with defined pathologies, from Southeast Brazil. We also analysed the structure of additional mitochondrial genes (ND4/CR4, COIII and COII) since the maxicircle is used for clustering Trypanosoma cruzi strains into three clades/haplogroups. We conclude that maxicircle genes do not discriminate parasite populations which induce IF or CCHD forms. Interestingly, the great majority of the analysed isolates belong to T cruzi 11 (discrete typing unit, (DTU) IIb) genotype. This scenario is at variance with the prevalence of hybrid (DTU IId) human isolates in Bolivia, Chile and Argentina. The distribution of WT and deleted ND7 and ND4 genes in T cruzi strains suggests that mutations in the two genes occurred in different ancestrals in the T cruzi 11 cluster, allowing the identification of at least three mitochondrial sub-lineages within this group. The observation that T. cruzi strains accumulate mutations in several genes coding for complex I subunits favours the hypothesis that complex I may have a limited activity in this parasite. (C) 2009 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Genetic similarity between staphylococcus sp isolated from human and hospital settings, and susceptibility to different antimicrobials

Foram coletadas 143 amostras de mãos de humanos e camas hospitalares, através de swabs no caldo BHI, em um hospital escola da cidade de Ribeirão Preto/SP. As amostras coletadas foram incubadas a 37ºC por 24 horas e após este período as culturas foram semeadas em placas de Petri contendo agar Staphylococcus Médium 110. As colônias típicas do gênero Staphylococcus foram colhidas e estocados a 4ºC até o momento de elaboração das provas de catalase, manitol, hemólise, DNAse e coagulase. As cepas isoladas foram analisadas através da técnica de RAPD-PCR para verificar o grau de similaridade. A sensibilidade das cepas isoladas foi testada frente a 10 diferentes antibióticos. Das 92 cepas de Staphylococcus sp isoladas, 67 (72,8%) foram identificados como Staphylococcus coagulase-negativas e 25 (27,2%) como Staphylococcus coagulase-positivas. A análise de similaridade mostrou uma grande heterogeneidade entre as cepas, entretanto foram isoladas algumas cepas com 100% de similaridade. Resistência a oxacilina foi encontrada em 39 (42%) cepas. Duas cepas de estafilococos coagulase-negativos mostraram-se resistentes a vancomicina. Onze cepas (12%) de estafilococos foram consideradas multirresistentes. Medidas de desinfecção das mãos de pessoal e dos leitos hospitalares e a racionalização do uso indiscriminado de antibióticos podem contribuir para a queda da transmissão de patógenos e diminuição da pressão de seleção, e conseqüentemente diminuindo a freqüência e letalidade das infecções nosocomiais.

Short Report: Heterogeneity of Leishmania infantum chagasi Kinetoplast DNA in Teresina (Brazil)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Geographical variation in genetic structure of an Atlantic Coastal Forest frog reveals regional differences in habitat stability

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Variance heterogeneity for milk yield in Brazilian and Colombian Holstein herds

Heterogeneity of variances for milk yield (MY) was determined for Brazilian and Colombian herds. The herds were grouped as high or low variability within each country, using as criterion the phenotypic standard deviation (PSD) of MY in the contemporary groups of cows, from the first to the sixth calving. Brazilian and Colombian herds with PSD greater than 1,168 kg or 1,012 kg, respectively, were classified as high variability while the herd groups with values lower than those were classified as low variability. The genetic parameters for MY within each herd group were estimated using bivariate analysis in an animal model and the restricted maximum likelihood method with a derivative free algorithm, using 72,280 first lactations of cows, daughters of 1,880 sires. Heterogeneous variances were found, and Brazilian herds with high PSD had the greatest additive and residual genetic variances and heritability coefficients for MY. MY genetic correlation coefficients between herds of high and low variability within each country were 0.96 and 0.93 while between countries they varied from 0.72 to 0.81, suggesting that there was a reclassification of animals in the two countries and also heterogeneity of variances. This phenomenon leads to the questioning of the strategy of imported semen usage and the need to do genetic evaluations to identify sires with greater genetic potential for (sub) tropical environmental conditions.

Cryptic Genetic Diversity Is Paramount in Small-Bodied Amphibians of the Genus Euparkerella (Anura: Craugastoridae) Endemic to the Brazilian Atlantic Forest

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Cluster and meta-analyses of genetic parameters for feed intake traits in growing beef cattle

A data set based on 50 studies including feed intake and utilization traits was used to perform a meta-analysis to obtain pooled estimates using the variance between studies of genetic parameters for average daily gain (ADG); residual feed intake (RFI); metabolic body weight (MBW); feed conversion ratio (FCR); and daily dry matter intake (DMI) in beef cattle. The total data set included 128 heritability and 122 genetic correlation estimates published in the literature from 1961 to 2012. The meta-analysis was performed using a random effects model where the restricted maximum likelihood estimator was used to evaluate variances among clusters. Also, a meta-analysis using the method of cluster analysis was used to group the heritability estimates. Two clusters were obtained for each trait by different variables. It was observed, for all traits, that the heterogeneity of variance was significant between clusters and studies for genetic correlation estimates. The pooled estimates, adding the variance between clusters, for direct heritability estimates for ADG, DMI, RFI, MBW and FCR were 0.32 +/- 0.04, 0.39 +/- 0.03, 0.31 +/- 0.02, 0.31 +/- 0.03 and 0.26 +/- 0.03, respectively. Pooled genetic correlation estimates ranged from -0.15 to 0.67 among ADG, DMI, RFI, MBW and FCR. These pooled estimates of genetic parameters could be used to solve genetic prediction equations in populations where data is insufficient for variance component estimation. Cluster analysis is recommended as a statistical procedure to combine results from different studies to account for heterogeneity.

Female fertility in a Guzerat dairy subpopulation: Heterogeneity of variance components for calving intervals

The objectives of the present study were to determine if variance components of calving intervals varied with age at calving and if considering calving intervals as a longitudinal trait would be a useful approach for fertility analysis of Zebu dairy herds. With these purposes, calving records from females born from 1940 to 2006 in a Guzerat dairy subpopulation in Brazil were analyzed. The fixed effects of contemporary groups, formed by year and farm at birth or at calving, and the regressions of age at calving, equivalent inbreeding coefficient and day of the year on the studied traits were considered in the statistical models. In one approach, calving intervals (Cl) were analyzed as a single trait, by fitting a statistical model on which both animal and permanent environment effects were adjusted for the effect of age at calving by random regression. In a second approach, a four-trait analysis was conducted, including age at first calving (AFC) and three different female categories for the calving intervals: first calving females; young females (less than 80 months old, but not first calving); or mature females (80 months old or more). Finally, a two-trait analysis was performed, also including AFC and Cl, but calving intervals were regarded as a single trait in a repeatability model. Additionally, the ranking of sires was compared among approaches. Calving intervals decreased with age until females were about 80 months old, remaining nearly constant after that age. A quasi-linear increase of 11.5 days on the calving intervals was observed for each 10% increase in the female's equivalent inbreeding coefficient. The heritability of AFC was 0.37. For Cl. the genetic-phenotypic variance ratios ranged from 0.064 to 0.141, depending on the approach and on ages at calving. Differences among genetic variance components for calving intervals were observed along the animal's lifetime. Those differences confirmed the longitudinal aspect of that trait, indicating the importance of such consideration when accessing fertility of Zebu dairy females, especially in situations where the available information relies on their calving intervals. Spearman rank correlations among approaches ranged from 0.90 to 0.95, and changes observed in the ranking of sires suggested that the genetic progress of the population could be affected by the approach chosen for the analysis of calving intervals. (C) 2012 Elsevier ay. All rights reserved.

Genetic analyses of smoking initiation, persistence, quantity, and age-at-onset of regular cigarette use in Brazilian families: the Baependi Heart Study

Background: The purpose of this study was to estimate the genetic influences on the initiation of cigarette smoking, the persistence, quantity and age-at-onset of regular cigarette use in Brazilian families. Methods: The data set consisted of 1,694 individuals enrolled in the Baependi Heart Study. The heritability and the heterogeneity in genetic and environmental variance components by gender were estimated from variance components approaches, using the SOLAR (Sequential Oligogenic Linkage Analysis Routines) computer package. The mixed-effects Cox model was used for the genetic analysis of the age-at onset of regular cigarette use. Results: The heritability estimates were high (> 50%) for smoking initiation and were intermediate, ranging from 23.4 to 31.9%, for smoking persistence and quantity. Significant evidence for heterogeneity in variance components by gender was observed for smoking initiation and age-at-onset of regular cigarette use. Genetic factors play an important role in the interindividual variation of these phenotypes in females, while in males there is a predominant environmental component, which could be explained by greater social influences in the initiation of tobacco use. Conclusions: Significant heritabilities were observed in smoking phenotypes for both males and females from the Brazilian population. These data add to the literature and are concordant with the notion of significant biological determination in smoking behavior. Samples from the Baependi Heart Study may be valuable for the mapping of genetic loci that modulate this complex biological trait.

The genetic history of Italians: new-insights from uniparentally-inherited markers

Genetic differences among human groups can be ascribed both to the broad-scale extents of pre-historical and historical migrations and to the fine-scale impacts of socio-cultural and geographic heterogeneity. In this thesis, the genetic information provided by uniparental markers were exploited to address different aspects of the Italian population history, by combining macro- and micro-geographic investigations at different spatial and temporal scales. To firstly assess the overall Italian variability, Y-chromosome and mtDNA markers were deeply typed in ~900 individuals from continental Italy, Sicily and Sardinia. Sex-biased patterns and contrasting demographic histories were observed for males and females. Differential European and Mediterranean contributions were invoked to explain the paternal genetic sub-structure observed in peninsular Italy, compared to the homogeneous maternal genetic landscape. If Neolithic showed to be one principal determinant of the detected paternal structure, local insights into specific Italian regional contexts highlighted the importance of Post-Neolithic contributions. Among them, migrations from the Balkans (particularly Greece) during late Metal Ages, played a relevant role in the cultural and genetic transitions occurred in Sicily and Southern Italy. On a finer geographic and temporal perspective, the more recent layers of Italian genetic history and some aspects of the gene-culture interaction were assessed by exploring the genetic variability within two “marginal populations”: Arbereshe of Southern Italy and Partecipanza in Northern Italy. The Arbereshe are Albanian-speaking communities settled in Sicily and Calabria since the end of Middle Ages. Despite sharing common genetic and cultural backgrounds, these groups revealed diverging micro-evolutionary histories, implying different founding events and different patterns of cultural isolation and local admixture. Partecipanza is an idiosyncratic institution of Medieval origin aimed at sharing and devolving collective lands. This case-study exemplified that socio-economic stratification within the same population may induce sex-biased genetic structuring and the maintenance of otherwise hidden historical genetic traces.

Molecular genetic investigation of the Neolithic population history in the western Carpathian Basin

Der Fokus dieser Dissertation ist die populationsgenetische Analyse der neolithischen Bevölkerungswechsel in den 6.-5. Jahrtausende vor Christus, die im westlichen Karpatenbecken stattfanden. Die Zielsetzung der Studie war, mittels der Analyse von mitochondrialer und Y-chromosomaler aDNA, den Genpool der sechs neolithischen und kupferzeitlichen Populationen zu untersuchen und die daraus resultierenden Ergebnisse mit anderen prähistorischen und modernen genetischen Daten zu vergleichen.rnInsgesamt wurden 323 Individuen aus 32 ungarischen, kroatischen und slowakischen Fundplätzen beprobt und bearbeitet in den archäogenetischen Laboren der Johannes Gutenberg-Universität in Mainz. Die DNA Ergebnisse wurden mit verschiedenen populationsgenetischen Methoden ausgewertet. Vergleichsdaten von prähistorischen und modernen eurasiatischen Populationen wurden dazu gesammelt.rnDie HVS-I Region der mitochondrialen DNA konnten bei 256 Individuen reproduziert und authentifiziert werden (mit einer Erfolgsrate von 85.9%). Die Typisierung der HVS-II Region war in 80 Fällen erfolgreich. Testend alle gut erhaltene Proben, die Y-chromosomale Haplogruppe konnte in 33 männlichen Individuen typisiert werden.rnDie neolithischen, mitochondrialen Haplogruppen deuten auf eine hohe Variabilität des maternalen Genpools hin. Sowohl die mitochondrialen als auch die Y-chromosomalen Daten lassen Rückschlüsse auf eine nah-östliche bzw. südwestasiatische Herkunft der frühen Bauern zu. Die Starčevo- und linearbandkermaischen-Populationen in westlichem Karpatenbecken (letztere abgekürzt als LBKT) und die linearbandkermaischen-Population in Mitteleuropa (LBK) haben so starke genetische Ähnlichkeit, dass die Verbreitung der LBK nach Mitteleuropa mit vorangegangenen Wanderungsereignissen zu erklären ist. Die Transdanubische aDNA Daten zeigen hohe Affinität zu den publizierten prähistorischen aDNA Datensätzen von Mitteleuropa aus den 6.-4. Jahrtausende vor Chr. Die maternal-genetische Variabilität der Starčevo-Population konnte auch innerhalb der nachfolgenden Populationen Transdanubiens festgestellt werden. Nur kleinere Infiltrationen und Immigrationsereignissen konnten während der Vinča-, LBKT-, Sopot- und Balaton-Lasinja-Kultur in Transdanubien identifiziert werden. Zwischen den transdanubischen Regionen konnten mögliche genetische Unterschiede nur in der LBKT und in der Lengyel-Periode beobachtet werden, als sich die nördlichen Gruppen von den südlichen Populationen trennten. rnDie festgestellte Heterogenität der mtDNA in Zusammenhang mit der Y-chromosomalen Homogenität in den Starčevo- und LBK-Populationen, weisen auf patrilokale Residenzregeln und patrilineare Abstammungsregeln in den ersten Bauergemeinschaften hin. rnObwohl die hier präsentierten Daten einen großen Fortschritt in der Forschung von aDNA und Neolithikum des Karpatenbeckens und Mitteleuropas bedeuten, werfen sie auch mehrere Fragen auf, deren Beantwortung durch zukünftige Genomforschungen erbracht werden könnte.