Estimates of genetic parameters, and cluster and principal components analyses of breeding values related to egg production traits in a White Leghorn population

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

Smoking status and tumor necrosis factor-alpha mediated systemic inflammation in COPD patients

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

Internal genetic structure and outcrossing rate in a natural population of Araucaria angustifolia (Bert.) O. Kuntze

The internal genetic structure and outcrossing rate of a population of Araucaria angustifolia (Bert.) O. Kuntze were investigated using 16 allozyme loci. Estimates of the mean number of alleles per loci (1.6), percentage of polymorphic loci (43.8%), and expected genetic diversity (0.170) were similar to those obtained for other gymnosperms. The analysis of spatial autocorrelation demonstrated the presence of internal structure in the first distance classes (up to 70 m), suggesting the presence of family structure. The outcrossing rate was high (0.956), as expected for a dioecious species. However, it was different from unity, indicating outcrossings between related individuals and corroborating the presence of internal genetic structure. The results of this study have implications for the methodologies used in conservation collections and for the use or analysis of this forest species. © The American Genetic Association. 2006. All rights reserved.

DNA repair gene polymorphism is associated with the genetic basis of atherosclerotic coronary artery disease

Background: Atherosclerotic coronary artery disease (CAD) is a multifactorial process that appears to be caused by the interaction of environmental risk factors with multiple predisposing genes. It is nowadays accepted that increased levels of DNA damage induced by xenobiotics play an important role in the early phases of atherogenesis. Therefore, in this study, we focus on determining whether genetic variations in xenobiotic-metabolizing [glutathione-S-transferase theta 1 (GSTT1), glutathione-S-transferase mu 1 (GSTM1), cytochrome P450 IIEI (CYP2E1)] and DNA repair [X-ray cross-complementing group 1 (XRCC1)] genes might be associated with increased risk for CAD. Methods: A case-control study was conducted with 400 individuals who underwent subjected to coronary angiography. A total of 299 were patients diagnosed with effective coronary atherosclerosis (case group; >20% obstructive lesion), and 101 (control group) were individuals diagnosed as negative for CAD (<20% obstructive lesions). The polymorphism identifications for GSTM1 and GSTT1, and for CYP2E1 and XRCC1 genes were performed by polymerase chain reaction (PCR) amplification and by PCR-RFLP, respectively. Results and conclusions: The XRCC1 homozygous wild-type genotype Arg/Arg for codon 399 was statistically less pronounced in the case subjects (21.4%) than in controls (38.5%); individuals with the variant XRCC1 genotype had a 2.3-fold increased risk for coronary atherosclerosis than individuals with the wild-type genotype (OR=2.3, 95% CI=1.13-4.69). Conversely, no association between GSTM1, GSTT1, and CYP2E1gene polymorphisms and coronary atherosclerosis was detected. The results provide evidence of the role of DNA damage and repair in cardiovascular disease. © 2011 Elsevier Inc. All rights reserved.

Genetic and modifying factors that determine the risk of brain tumors

Some modifying factors may determine the risk of brain tumors. Until now, it could not be attempted to identify people at risk and also to improve significantly disease progression. Current therapy consists of surgical resection, followed by radiation therapy and chemotherapy. Despite of these treatments, the prognosis for patients is poor. In this review, we highlight general aspects concerning genetic alterations in brain tumors, namely astrocytomas, glioblastomas, oligodendrogliomas, medulloblastomas and ependymomas. The influence of these genetic alterations in patients' prognosis is discussed. Mutagen sensivity is associated with cancer risk. The convincing studies that linked DNA damages and DNA repair alterations with brain tumors are also described. Another important modifying factor is immunity. General immune response against cancer, tumor microenvironment and immune response, mechanisms of tumor escape, CNS tumor immunology, immune defects that impair anti-tumor systemic immunity in brain tumor patients and local immunosuppressive factors within CNS are also reviewed. New hope to treatment perspectives, as dendritic-cell-based vaccines is summarized too. Concluding, it seems well established that there is association between brain tumor risk and mutagen sensivity, which is highly heritable. Primary brain tumors cause depression in systemic host immunity; local immunosuppressive factors and immunological characteristics of tumor cells may explain the poor prognosis and DNA damages responses can alert immune system. However, it is necessary to clarify if individuals with both constitutional defects in immune functions and genetic instability have higher risk of developing brain tumors. Cytogenetic prospective studies and gene copy number variations analysis also must be performed in peripheral lymphocytes from brain tumor patients. © 2011 Bentham Science Publishers Ltd.

Association of IGF1 and KDM5A polymorphisms with performance, fatness and carcass traits in chickens

Two functional and positional candidate genes were selected in a region of chicken chromosome 1 (GGA1), based on their biological roles, and also where several quantitative trait loci (QTL) have been mapped and associated with performance, fatness and carcass traits in chickens. The insulin-like growth factor 1 (IGF1) gene has been associated with several physiological functions related to growth. The lysine (K)-specific demethylase 5A (KDM5A) gene participates in the epigenetic regulation of genes involved with the cell cycle. Our objective was to find associations of selected single-nucleotide polymorphisms (SNPs) in these genes with performance, fatness and carcass traits in 165 F2 chickens from a resource population. In the IGF1 gene, 17 SNPs were detected, and in the KDM5A gene, nine SNPs were detected. IGF1 SNP c. 47673G > A was associated with body weight and haematocrit percentage, and also with feed intake and percentages of abdominal fat and gizzard genotype × sex interactions. KDM5A SNP c. 34208C > T genotype × sex interaction affected body weight, feed intake, percentages of abdominal fat (p = 0. 0001), carcass, gizzard and haematocrit. A strong association of the diplotype × sex interaction (p < 0. 0001) with abdominal fat was observed, and also associations with body weight, feed intake, percentages of carcass, drums and thighs, gizzard and haematocrit. Our findings suggest that the KDM5A gene might play an important role in the abdominal fat deposition in chickens. The IGF1 and KDM5A genes are strong candidates to explain the QTL mapped in this region of GGA1. © 2012 Institute of Plant Genetics, Polish Academy of Sciences, Poznan.

Genetic Diversity in the Modern Horse Illustrated from Genome-Wide SNP Data

Horses were domesticated from the Eurasian steppes 5,000-6,000 years ago. Since then, the use of horses for transportation, warfare, and agriculture, as well as selection for desired traits and fitness, has resulted in diverse populations distributed across the world, many of which have become or are in the process of becoming formally organized into closed, breeding populations (breeds). This report describes the use of a genome-wide set of autosomal SNPs and 814 horses from 36 breeds to provide the first detailed description of equine breed diversity. FST calculations, parsimony, and distance analysis demonstrated relationships among the breeds that largely reflect geographic origins and known breed histories. Low levels of population divergence were observed between breeds that are relatively early on in the process of breed development, and between those with high levels of within-breed diversity, whether due to large population size, ongoing outcrossing, or large within-breed phenotypic diversity. Populations with low within-breed diversity included those which have experienced population bottlenecks, have been under intense selective pressure, or are closed populations with long breed histories. These results provide new insights into the relationships among and the diversity within breeds of horses. In addition these results will facilitate future genome-wide association studies and investigations into genomic targets of selection. © 2013 Petersen et al.

Profiles of gene polymorphisms in cytokines and toll-like receptors with higher risk for gastric cancer

Background: Chronic inflammation and gastric carcinogenesis show a close association, so gene polymorphisms that modify the intensity of the inflammatory response may contribute to variations in gastric cancer risk. Aims: The purpose of this study was to investigate the combined effect of the pro- and anti-inflammatory cytokines and toll-like receptors polymorphisms on the chronic gastritis and gastric cancer risk in a Brazilian population sample. Methods: We evaluated 669 DNA samples (200 of gastric cancer [GC], 229 of chronic gastritis [CG], and 240 of healthy individuals [C]). Ten polymorphisms were genotyped: IL-1RN and TLR2 -196 to -174 del using the allele-specific PCR method and TNF-A (rs1800629; rs1799724), TNF-B (rs909253), IL-8 (rs4073; rs2227532), IL-10 (rs1800872) and TLR4 (rs4986790; rs4986791) using PCR-RFLP. Results: Polymorphisms TNF-A-308G/A, IL-8-251A/T, TNF-B + 252A/G and TLR4 + 1196C/T were not associated with risk of any gastric lesion. However, an association with increased risk for GC was observed for polymorphisms IL-1RNL/2 (p < 0.001), TNF-A-857C/T (p = 0.022), IL-8-845T/C (p < 0.001), IL-10-592C/A (p < 0.001), TLR2ins/del (p < 0.001), and TLR4 + 896A/G (p = 0.033). In CG, an association was observed only with polymorphisms IL-1RNL/2 and IL-10-592A/C (p < 0.001 for both). A combined analysis of these six polymorphisms associated with GC revealed a profile with two to four combined genotypes which confer a higher risk of gastric carcinogenesis, with an OR increased 2.95-fold to 50.4-fold, highlighting the combinations IL-1RN2/TNF-A-857T/IL-8-845C, IL-1RN2/IL-8-845C/TLR2del, IL-1RN2/IL-10-592A/TLR4 + 896G, IL-10-592A/TLR2del/ TLR4 + 896G, and IL-1RN2/TNFA-857T/IL8-845C/TLR2del. Conclusions: Our findings evidenced that the combined effect of polymorphisms in genes involved in the inflammatory process may potentiate the risk of gastric cancer, thus emphasizing the importance of evaluating multiple polymorphisms together. © 2012 Springer Science+Business Media New York.

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.

Genetic evaluation using multi-trait and random regression models in Simmental beef cattle

The Brazilian Association of Simmental and Simbrasil Cattle Farmers provided 29,510 records from 10,659 Simmental beef cattle; these were used to estimate (co)variance components and genetic parameters for weights in the growth trajectory, based on multi-trait (MTM) and random regression models (RRM). The (co)variance components and genetic parameters were estimated by restricted maximum likelihood. In the MTM analysis, the likelihood ratio test was used to determine the significance of random effects included in the model and to define the most appropriate model. All random effects were significant and included in the final model. In the RRM analysis, different adjustments of polynomial orders were compared for 5 different criteria to choose the best fit model. An RRM of third order for the direct additive genetic, direct permanent environmental, maternal additive genetic, and maternal permanent environment effects was sufficient to model variance structures in the growth trajectory of the animals. The (co)variance components were generally similar in MTM and RRM. Direct heritabilities of MTM were slightly lower than RRM and varied from 0.04 to 0.42 and 0.16 to 0.45, respectively. Additive direct correlations were mostly positive and of high magnitude, being highest at closest ages. Considering the results and that pre-adjustment of the weights to standard ages is not required, RRM is recommended for genetic evaluation of Simmental beef cattle in Brazil. ©FUNPEC-RP.

Polymorphisms of estrogen receptor-α gene in Brazilian women with high breast density after menopause

The association of genetic polymorphism in the estrogen receptor alpha (ERα) gene and risk for diseases including breast cancer (BC) has been the subject of great interest. Objective: Checking on women with high breast density after menopause, the frequency of the Pvull and Xbal polymorphisms of the ERα gene and the correlation between them and the known risk factors for breast cancer. Method: Observational study with 308 women between 45 and 65 years old with high breast density, without hormonal therapy, menstruation for a year or more, breast and ovarian cancer history. It was characterized in clinical history and physical examination: menarche, menopause, parity, family history of BC, smoking, alcohol intake and body mass index. Results: The allelic and genotypic frequencies for ERα-Pvull and Xbal: p=43.99%; p=56.01%; pp=32.14%; Pp=47.73% and PP=20.13%; X=41.56%; x=58.44%; xx=33.44%; Xx=50.00% and XX=16.56%, respectively. The most frequent risk factors for BC: menarche before 12 years old (35.38%), nulliparity or first child after 28 years old (41.66%), family history of BC (19.16%) and overweight/obesity (62.01%). Conclusion: Allelic and genotypic distribution similar to literature. The risk factors for BC were more prevalent in women with high breast density but without significant associations with these polymorphisms. © 2013 Informa UK Ltd. All rights reserved.

Genetic parameters and principal component analysis for egg production from White Leghorn hens

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estudo da habilidade de permanência de fêmeas da raça Canchim aos 76 meses de idade

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)