HTR1B and HTR2C in autism spectrum disorders in Brazilian families

Autism spectrum disorders (ASD) is a group of behaviorally defined neuro developmental disabilities characterized by multiple genetic etiologies and a complex presentation. Several studies suggest the involvement of the serotonin system in the development of ASD, but only few have investigated serotonin receptors. We have performed a case-control and a family-based study with 9 polymorphisms mapped to two serotonin receptor genes (HTR1B and HTR2C) in 252 Brazilian male ASD patients of European ancestry. These analyses showed evidence of undertransmission of the HTR1B haplotypes containing alleles -161G and -261A at HTR1B gene to ASD (P=0.003), but no involvement of HTR2C to the predisposition to this disease. Considering the relatively low level of statistical significance and the power of our sample, further studies are required to confirm the association of these serotonin-related genes and ASD. (C) 2008 Elsevier B.V. All rights reserved.

Novel Statistical Methods in Quantitative Genetics : Modeling Genetic Variance for Quantitative Trait Loci Mapping and Genomic Evaluation

This thesis develops and evaluates statistical methods for different types of genetic analyses, including quantitative trait loci (QTL) analysis, genome-wide association study (GWAS), and genomic evaluation. The main contribution of the thesis is to provide novel insights in modeling genetic variance, especially via random effects models. In variance component QTL analysis, a full likelihood model accounting for uncertainty in the identity-by-descent (IBD) matrix was developed. It was found to be able to correctly adjust the bias in genetic variance component estimation and gain power in QTL mapping in terms of precision.  Double hierarchical generalized linear models, and a non-iterative simplified version, were implemented and applied to fit data of an entire genome. These whole genome models were shown to have good performance in both QTL mapping and genomic prediction. A re-analysis of a publicly available GWAS data set identified significant loci in Arabidopsis that control phenotypic variance instead of mean, which validated the idea of variance-controlling genes.  The works in the thesis are accompanied by R packages available online, including a general statistical tool for fitting random effects models (hglm), an efficient generalized ridge regression for high-dimensional data (bigRR), a double-layer mixed model for genomic data analysis (iQTL), a stochastic IBD matrix calculator (MCIBD), a computational interface for QTL mapping (qtl.outbred), and a GWAS analysis tool for mapping variance-controlling loci (vGWAS).

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in upto 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 x 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for similar to 2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous systemin obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Estudo da associação de elementos traços com a fração orgânica e inorgânica do carvão do leão

O presente trabalho refere-se à determinação dos elementos cobre, chumbo, zinco, cobalto, níquel, cromo, vanádio e manganês no carvão da Mina do Leão, com o objetivo de verificar a distribuição e ocorrência dos mesmos, com ênfase ao estudo da associação com as frações orgânica e inorgânica do carvão. O estudo da associação revelou que o cobre, cobalto, níquel, cromo e vanádio, estão associados à fração orgânica do carvão. O chumbo e o zinco, estão predominantemente associados a fração orgânica, contudo, para altos teores de cinzas, verifica-se também associação com a fração inorgânica. O manganês, está dominantemente associado à fração inorgânica.

Presence and morphology of the molar tubercle according to dentition, hemi-arch and sex

The purpose of this study was to assess the presence and the degree of expression of the molar tubercle according to sex, dentition and hemi-arches. Study casts of 126 patients were assessed, and those were under orthodontic treatment at the University of Franca, UNIFRAN; they were from both sexs, from 4 to 13 years old. The upper second primary molars and the upper first permanent molars, from both sides, were evaluated regarding the presence and the degree of expression of the molar tubercle. For an association study, the qui-square test was utilized. The concordance about the presence or absence of the molar tubercle according to dentition, hemi-arch and sex, was estimated by the Kappa Statistics. There was a sexual dimorphism concerning the presence/absence of the molar tubercle (p=0.009), however there was no significant association between the degree of expression of the tubercle and the sex (p=0.791). The molar tubercle was more frequently observed in the male sex, in upper second primary molars and in the form of depression. There was a significant and "moderate" concordance between the left and right sides in primary dentition (k=0.596), there was a "good" concordance in permanent dentition (k=0.708) and a "weak" and significant concordance between the presence of the molar tubercle and dentition (k=0.207).

Determinants of blood pressure in type 2 diabetic subjects with high occurrence of inadequate glycemic control

Study design: Association study Objective: To analyze the association between different biological/behavioral risk factors and blood pressure in a sample of type 2 diabetes mellitus patients with poor glycemic control. Methods: A sample of 121 type 2 diabetic patients was selected in the Public Healthcare System in a middle size Brazilian city. Blood pressure was measured using an aneroid device, previously calibrated. Six determinants of blood pressure were taken into count: age, hypoglycemic agents, general obesity, abdominal obesity, eating behaviors and physical activity level. Results: The type 2 diabetic patients presented mean age of 60.1±8.9 years-old and, at least, one risk factor. Eating behaviors (OR adj= 0.31 [0.12-0.75]) and sports practice (OR adj= 0.12 [0.02-0.75]) constituted protective factors associated with lower systolic blood pressure. On the other hand, age was positively associated with high systolic blood pressure (OR adj= 3.81 [1.39-10.38]). Patients with 5-6 risk factors, presented higher values of systolic and (F= 3.857; p= 0.011 [post hoc with p= 0.039]), diastolic blood pressure (F= 4.158; p= 0.008 [post hoc with p= 0.036]) and increased occurrence of hypertension (p= 0.010). Conclusion: Our findings indicate that, behavioral variables were important determinants of blood pressure in type 2 diabetic patients with poor glycemic control and clustering of behavioral and biological risk factors increase the hypertension occurrence.

How bioinformatics enables livestock applied sciences in the genomic era

This review paper presents the three main approaches currently used in livestock genomic sciences where the bioinfomatics plays a critical role. They are named as Genomic Selection (GS), Genome Wide Association Study (GWAS) and Signatures of Selection (SS). The subsides for the construction of this article were generated in a current project (started in 2011), so called Zebu Genome Consortium (ZGC), which joins researchers from different institutions and countries, aiming to scientifically explore genomic information of Bos taurus indicus cattle breeds and deliver useful information to breeders and academic community, specially from the tropical regions of the world. © 2012 Springer-Verlag.

Genome-Wide Analysis Reveals Selection for Important Traits in Domestic Horse Breeds

Intense selective pressures applied over short evolutionary time have resulted in homogeneity within, but substantial variation among, horse breeds. Utilizing this population structure, 744 individuals from 33 breeds, and a 54,000 SNP genotyping array, breed-specific targets of selection were identified using an FST-based statistic calculated in 500-kb windows across the genome. A 5.5-Mb region of ECA18, in which the myostatin (MSTN) gene was centered, contained the highest signature of selection in both the Paint and Quarter Horse. Gene sequencing and histological analysis of gluteal muscle biopsies showed a promoter variant and intronic SNP of MSTN were each significantly associated with higher Type 2B and lower Type 1 muscle fiber proportions in the Quarter Horse, demonstrating a functional consequence of selection at this locus. Signatures of selection on ECA23 in all gaited breeds in the sample led to the identification of a shared, 186-kb haplotype including two doublesex related mab transcription factor genes (DMRT2 and 3). The recent identification of a DMRT3 mutation within this haplotype, which appears necessary for the ability to perform alternative gaits, provides further evidence for selection at this locus. Finally, putative loci for the determination of size were identified in the draft breeds and the Miniature horse on ECA11, as well as when signatures of selection surrounding candidate genes at other loci were examined. This work provides further evidence of the importance of MSTN in racing breeds, provides strong evidence for selection upon gait and size, and illustrates the potential for population-based techniques to find genomic regions driving important phenotypes in the modern horse. © 2013 Petersen et al.

Morphological and Genomic Differences Between Cutting and Racing Lines of Quarter Horses

To investigate morphological and genomic differences between cutting and racing lines of Quarter Horses, 120 racing and 68 cutting animals of both sexes, registered at the Brazilian Association of Quarter Horse Breeders, were used. Blood samples were collected, and the following physical traits were measured: weight; height at withers; body length; length of the shank, pastern, rump, head, and neck; and chest, shank, and hoof circumference. For analysis of genomic differences, 54,602 single-nucleotide polymorphisms (SNPs) were genotyped using the Equine SNP50 BeadChip, and the quality of individual and SNP genotype data were evaluated. The fixation index, FST, was used to identify genome regions that were altered in the lines by selection. The results showed significant differences between the lines in all physical traits. Quality control led to the exclusion of four cutting animals with a call rate of <0.95. After filtering, 12,544, 13,815, and 13,370 SNPs were excluded for the whole population (n = 184), the 120 racing animals, and the 64 cutting animals, respectively. The number of informative polymorphisms detected in each line and in the whole population indicated that the Equine SNP50 BeadChip can be used in genetic studies of Quarter Horses. The fixation index, FST, identified 2,558 genome regions that may have been modified by divergent selection. © 2013 Elsevier Inc.

Papel de polimorfismos genéticos nos genes IL10, TNF e LTA na hanseníase

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Epidemiologia genética em hanseníase: estudo de associação da região genômica candidata 6p21 e do gene TLR1

Pós-graduação em Doenças Tropicais - FMB

Tracoma em crianças do Ensino Fundamental do município de Bauru - Estado de São Paulo, Brasil

Pós-graduação em Bases Gerais da Cirurgia - FMB

Associação de polimorfismos de nucleotídeo único com características de crescimento e reprodutivas em bovinos Canchim

Pós-graduação em Genética e Melhoramento Animal - FCAV

Estudo de associação genômica e análise de enriquecimento genético da criotolerância espermática em bovinos da raça Nelore

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Síntese, caracterização e estudo da auto-associação em solução aquosa de derivados anfifílicos zwiteriônicos de quitosana

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)