Allelic variants of XRCC1 and XRCC3 repair genes and susceptibility of oral cancer in Brazilian patients

Background: The capacity for DNA repair is essential in maintaining cellular functions and homeostasis; however, this capacity can be altered based on DNA sequence variations in DNA repair genes, which may contribute to the onset of cancer. Many single-nucleotide polymorphisms (SNPs) in repair genes have been found to be associated with oral cancer. The aim of this study was to investigate the relationship between the presence of allelic variants Arg194Trp (rs:1799782) and Arg399Gln (rs: 25487) of XRCC1 gene and Thr241Met (rs: 861539) of XRCC3 gene and susceptibility to oral cancer. We also attempted to correlate the frequencies obtained for each of the SNPs to histopathological parameters. Methods: A case-control study was conducted with genomic DNA from 150 patients with oral squamous cell carcinomas and 150 controls. SNPs were genotyped by RFLP-PCR. Results: The presence of the polymorphic variants of the XRCC1 gene within codon 194 (OR 0.82, 95% CI: 0.44-1.51) and codon 399 (OR 0.94, 95% CI: 0.59-1.50) and within the XRCC3 gene (OR 0.72; 95% CI: 0.45-1.16) were not associated with an increased risk of oral cancer. A combinational analysis of SNPs in both genes indicated no association. The presence of the allelic variants of these two genes had no statistically significant effect on tumor differentiation, lymph node invasion or tumor size. Conclusions: These results suggest that allelic variants of XRCC1 and XRCC3 are not suitable markers for susceptibility to carcinomas of the oral cavity and are also not related to the later stages of such tumors. © 2012 John Wiley & Sons A/S.

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.

Development and validation of a D-loop mtDNA SNP assay for the screening of specimens in forensic casework

Mitochondrial DNA (mtDNA) analysis is usually a last resort in routine forensic DNA casework. However, it has become a powerful tool for the analysis of highly degraded samples or samples containing too little or no nuclear DNA, such as old bones and hair shafts. The gold standard methodology still constitutes the direct sequencing of polymerase chain reaction (PCR) products or cloned amplicons from the HVS-1 and HVS-2 (hypervariable segment) control region segments. Identifications using mtDNA are time consuming, expensive and can be very complex, depending on the amount and nature of the material being tested. The main goal of this work is to develop a less labour-intensive and less expensive screening method for mtDNA analysis, in order to aid in the exclusion of non-matching samples and as a presumptive test prior to final confirmatory DNA sequencing. We have selected 14 highly discriminatory single nucleotide polymorphisms (SNPs) based on simulations performed by Salas and Amigo (2010) [1] to be typed using SNaPShotTM (Applied Biosystems, Foster City, CA, USA). The assay was validated by typing more than 100 HVS-1/HVS-2 sequenced samples. No differences were observed between the SNP typing and DNA sequencing when results were compared, with the exception of allelic dropouts observed in a few haplotypes. Haplotype diversity simulations were performed using 172 mtDNA sequences representative of the Brazilian population and a score of 0.9794 was obtained when the 14 SNPs were used, showing that the theoretical prediction approach for the selection of highly discriminatory SNPs suggested by Salas and Amigo (2010) [1] was confirmed in the population studied. As the main goal of the work is to develop a screening assay to skip the sequencing of all samples in a particular case, a pair-wise comparison of the sequences was done using the selected SNPs. When both HVS-1/HVS-2 SNPs were used for simulations, at least two differences were observed in 93.2% of the comparisons performed. The assay was validated with casework samples. Results show that the method is straightforward and can be used for exclusionary purposes, saving time and laboratory resources. The assay confirms the theoretic prediction suggested by Salas and Amigo (2010) [1]. All forensic advantages, such as high sensitivity and power of discrimination, as also the disadvantages, such as the occurrence of allele dropouts, are discussed throughout the article. © 2013 Elsevier B.V.

Genome-wide association study for backfat thickness in Canchim beef cattle using Random Forest approach

Background: Meat quality involves many traits, such as marbling, tenderness, juiciness, and backfat thickness, all of which require attention from livestock producers. Backfat thickness improvement by means of traditional selection techniques in Canchim beef cattle has been challenging due to its low heritability, and it is measured late in an animal's life. Therefore, the implementation of new methodologies for identification of single nucleotide polymorphisms (SNPs) linked to backfat thickness are an important strategy for genetic improvement of carcass and meat quality.Results: The set of SNPs identified by the random forest approach explained as much as 50% of the deregressed estimated breeding value (dEBV) variance associated with backfat thickness, and a small set of 5 SNPs were able to explain 34% of the dEBV for backfat thickness. Several quantitative trait loci (QTL) for fat-related traits were found in the surrounding areas of the SNPs, as well as many genes with roles in lipid metabolism.Conclusions: These results provided a better understanding of the backfat deposition and regulation pathways, and can be considered a starting point for future implementation of a genomic selection program for backfat thickness in Canchim beef cattle. © 2013 Mokry et al.; licensee BioMed Central Ltd.

Genome-wide association study for birth weight in Nellore cattle points to previously described orthologous genes affecting human and bovine height

Background: Birth weight (BW) is an economically important trait in beef cattle, and is associated with growth- and stature-related traits and calving difficulty. One region of the cattle genome, located on Bos primigenius taurus chromosome 14 (BTA14), has been previously shown to be associated with stature by multiple independent studies, and contains orthologous genes affecting human height. A genome-wide association study (GWAS) for BW in Brazilian Nellore cattle (Bos primigenius indicus) was performed using estimated breeding values (EBVs) of 654 progeny-tested bulls genotyped for over 777,000 single nucleotide polymorphisms (SNPs).Results: The most significant SNP (rs133012258, PGC = 1.34 × 10-9), located at BTA14:25376827, explained 4.62% of the variance in BW EBVs. The surrounding 1 Mb region presented high identity with human, pig and mouse autosomes 8, 4 and 4, respectively, and contains the orthologous height genes PLAG1, CHCHD7, MOS, RPS20, LYN, RDHE2 (SDR16C5) and PENK. The region also overlapped 28 quantitative trait loci (QTLs) previously reported in literature by linkage mapping studies in cattle, including QTLs for birth weight, mature height, carcass weight, stature, pre-weaning average daily gain, calving ease, and gestation length.Conclusions: This study presents the first GWAS applying a high-density SNP panel to identify putative chromosome regions affecting birth weight in Nellore cattle. These results suggest that the QTLs on BTA14 associated with body size in taurine cattle (Bos primigenius taurus) also affect birth weight and size in zebu cattle (Bos primigenius indicus). © 2013 Utsunomiya et al.; licensee BioMed Central Ltd.

The Genome of Anopheles darlingi, the main neotropical malaria vector

Anopheles darlingi is the principal neotropical malaria vector, responsible for more than a million cases of malaria per year on the American continent. Anopheles darlingi diverged from the African and Asian malaria vectors ∼100 million years ago (mya) and successfully adapted to the New World environment. Here we present an annotated reference A. darlingi genome, sequenced from a wild population of males and females collected in the Brazilian Amazon. A total of 10 481 predicted protein-coding genes were annotated, 72% of which have their closest counterpart in Anopheles gambiae and 21% have highest similarity with other mosquito species. In spite of a long period of divergent evolution, conserved gene synteny was observed between A. darlingi and A. gambiae. More than 10 million single nucleotide polymorphisms and short indels with potential use as genetic markers were identified. Transposable elements correspond to 2.3% of the A. darlingi genome. Genes associated with hematophagy, immunity and insecticide resistance, directly involved in vectorhuman and vectorparasite interactions, were identified and discussed. This study represents the first effort to sequence the genome of a neotropical malaria vector, and opens a new window through which we can contemplate the evolutionary history of anopheline mosquitoes. It also provides valuable information that may lead to novel strategies to reduce malaria transmission on the South American continent. The A. darlingi genome is accessible at www.labinfo.lncc.br/index.php/anopheles- darlingi. © 2013 The Author(s).

Isolation and characterization of SNPs within HSC70 gene in the freshwater prawn Macrobrachium amazonicum

We report the discovery of 13 synonymous single nucleotide polymorphisms (SNPs) within a fragment of HSC70 gene in Macrobrachium amazonicum. Polymorphisms were assessed using the reference sequence of the HSC70 gene in Macrobrachium rosenbergii to the primers design. The minor allele frequency ranged from 0.011 to 0.213. None of the SNPs deviated significantly from Hardy-Weinberg equilibrium. These SNPs will be useful to access the genetic variation of populations and to the study of their relations with characteristics of interest for aquaculture. Both cases, favoring the conservation of the natural stocks of Amazon river prawn. © 2013 Springer Science+Business Media Dordrecht.

Genetic diversity of the HLA-G coding region in Amerindian populations from the Brazilian Amazon: a possible role of natural selection

HLA-G has an important role in the modulation of the maternal immune system during pregnancy, and evidence that balancing selection acts in the promoter and 3′UTR regions has been previously reported. To determine whether selection acts on the HLA-G coding region in the Amazon Rainforest, exons 2, 3 and 4 were analyzed in a sample of 142 Amerindians from nine villages of five isolated tribes that inhabit the Central Amazon. Six previously described single-nucleotide polymorphisms (SNPs) were identified and the Expectation-Maximization (EM) and PHASE algorithms were used to computationally reconstruct SNP haplotypes (HLA-G alleles). A new HLA-G allele, which originated in Amerindian populations by a crossing-over event between two widespread HLA-G alleles, was identified in 18 individuals. Neutrality tests evidenced that natural selection has a complex part in the HLA-G coding region. Although balancing selection is the type of selection that shapes variability at a local level (Native American populations), we have also shown that purifying selection may occur on a worldwide scale. Moreover, the balancing selection does not seem to act on the coding region as strongly as it acts on the flanking regulatory regions, and such coding signature may actually reflect a hitchhiking effect.Genes and Immunity advance online publication, 3 October 2013; doi:10.1038/gene.2013.47.

Estudo de SNPs do cromossomo Y na população do Estado do Espirito Santo, Brasil

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Uso da farmacogenética cardiovascular na análise e prevenção de doenças cardiovasculares e classificação em haplogrupos pelo cromossomo Y e DNA mitocondrial

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Prevalência de parasitas intestinais e caracterização genotípica de Giardia duodenalis em creche do município de Pratânia, estado de São Paulo

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Desenvolvimento de metodologia high-throughput para estudo populacional do mosquito Aedes aegypti e comparação de dados de genes mitocondriais

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

Fenótipo Lewis negativo: potencial fator de risco para infecção por cepa RH de Toxoplasma gondii em gestantes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Desequilíbrio de ligação e associação entre polimorfismos de base única com maciez da carne e espessura de gordura em bovinos Nelore utilizando painéis de alta densidade

Pós-graduação em Genética e Melhoramento Animal - FCAV