Human Platelet Polymorphism can be a genetic marker associated with HIV/HCV coinfection

To evaluate the associations of HPA polymorphisms -1, -3, and -5 with HIV/HCV coinfection were included in this study 60 HIV/HCV-coinfected patients from the Sao Paulo State health service centers. Data reported by Verdichio-Moraes et al. (2009: J. Med Virol 81:757-759) were used as the non-infected and HCV monoinfected groups. Human Platelet Polymorphism genotyping was performed in 60 Patients co-infected with HIV/HCV by PCR-SSP or PCR-RFLP. HIV subtyping and HCV genotyping was performed by RT-PCR followed sequencing. The data analyses were performed using the χ2 test or Fisher's Exact Test and the logistic regression model. Patients coinfected with HIV/HCV presented HCV either genotype 1 (78.3%) or non-1 (21.7%) and HIV either subtype B (85.0%) or non-B (15%). The Human Platelet Polymorphism-1a/1b genotype was more frequent (P < 0.05) in HIV/HCV coinfection than in HCV monoinfection and the allelic frequency of Human Platelet Polymorphism-5b in the Patients coinfected with HIV/HCV was higher (P < 0.05) than in HCV monoinfected cases and non-infected individuals. These data suggest that the presence of specific HPA allele on platelets could favor the existence of coinfection. On the other hand, Human Platelet Polymorphism-5a/5b was more frequent (P < 0.05) in HIV/HCV coinfected and HCV monoinfected groups than in the non-infected individuals, suggesting that this platelet genotype is related to HCV infection, regardless of HIV presence. Results suggest that the Human Platelet Polymorphism profile in HIV/HCV coinfected individuals differs from the one of both HCV monoinfected and non-infected population. So, the Human Platelet Polymorphism can be a genetic marker associated with HIV/HCV coinfection.

Genetic Mapping of Quantitative Trait Loci Associated with Bioenergy Traits, and The Assessment of Genetic Variability in Sweet Sorghum (Sorghum bicolor (L.). Moench)

Sweet sorghum, a botanical variety of sorghum is a potential source of bioenergy because high sugar levels accumulate in its stalks. The objectives of this study were to explore the global diversity of sweet sorghum germplasm, and map the genomic regions that are associated with bioenergy traits. In assessing diversity, 142 sweet sorghum accessions were evaluated with three marker types (SSR, SRAP, and morphological markers) to determine the degree of relatedness among the accessions. The traits measured (anthesis date [AD], plant height [PH], biomass yield [BY], and moisture content [MC]) were all significantly different (P<0.05) among accessions. Morphological marker clustered the accessions into five groups based on PH, MC and AD. The three traits accounted for 92.5% of the variation. There were four and five groups based on SRAP and SSR data respectively classifying accessions mainly on their origin or breeding history. The observed difference between SSR and SRAP based clusters could be attributed to the difference in marker type. SSRs amplify any region of the genome whereas SRAP amplify the open reading frames and promoter regions. Comparing the three marker-type clusters, the markers complimented each other in grouping accessions and would be valuable in assisting breeders to select appropriate lines for crossing. In evaluating QTLs that are associated with bioenergy traits, 165 recombinant inbred lines (RILs) were planted at four environments in Nebraska. A genetic linkage map constructed spanned a length of 1541.3 cM, and generated 18 linkage groups that aligned to the 10 sorghum chromosomes. Fourteen QTLs (6 for brix, 3 for BY, 2 each for AD and MC, and 1 for PH) were mapped. QTLs for the traits that were significantly correlated, colocalized in two clusters on linkage group Sbi01b. Both parents contributed beneficial alleles for most of traits measured, supporting the transgressive segregation in this population. Additional work is needed on exploiting the usefulness of chromosome 1 in breeding sorghum for bioenergy.

Thioredoxin interacting protein genetic variation is associated with diabetes and hypertension in the Brazilian general population

Objective: To investigate the relationship between TXNIP polymorphisms, diabetes and hypertension phenotypes in the Brazilian general population. Methods: Five hundred seventy-six individuals randomly selected from the general urban population according to the MONICA-WHO project guidelines were phenotyped for cardiovascular risk factors. A second, independent, sample composed of 487 family-trios from a different site was also selected. Nine TXNIP polymorphisms were studied. The potential association between TXNIP variability and glucose-phenotypes in children was also explored. TXNIP expression was quantified by real-time PCR in 53 samples from human smooth muscle cells primary culture. Results: TXNIP rs7211 and rs7212 polymorphisms were significantly associated with glucose and blood pressure related phenotypes. In multivariate logistic regression models the studied markers remained associated with diabetes even after adjustment for covariates. TXNIP rs7211 T/rs7212 G haplotype (present in approximately 17% of individuals) was significantly associated to diabetes in both samples. In children, the TXNIP rs7211 T/rs7212 G haplotype was associated with fasting insulin concentrations. Finally, cells harboring TXNIP rs7212 G allele presented higher TXNIP expression levels compared with carriers of TXNIP rs7212 CC genotype (p = 0.02). Conclusion: Carriers of TXNIP genetic variants presented higher TXNIP expression, early signs of glucose homeostasis derangement and increased susceptibility to chronic metabolic conditions such as diabetes and hypertension. Our data suggest that genetic variation in the TXNIP gene may act as a "common ground" modulator of both traits: diabetes and hypertension. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Kerteszia subgenus of Anopheles associated with the Brazilian Atlantic rainforest:current knowledge and future challenges

Abstract Background The Atlantic rainforest ecosystem, where bromeliads are abundant, provides an excellent environment for Kerteszia species, because these anophelines use the axils of those plants as larval habitat. Anopheles (K.) cruzii and Anopheles (K.) bellator are considered the primary vectors of malaria in the Atlantic forest. Although the incidence of malaria has declined in some areas of the Atlantic forest, autochthonous cases are still registered every year, with Anopheles cruzii being considered to be a primary vector of both human and simian Plasmodium. Methods Recent publications that addressed ecological aspects that are important for understanding the involvement of Kerteszia species in the epidemiology of malaria in the Atlantic rainforest in the Neotropical Region were analysed. Conclusion The current state of knowledge about Kerteszia species in relation to the Atlantic rainforest ecosystem was discussed. Emphasis was placed on ecological characteristics related to epidemiological aspects of this group of mosquitoes. The main objective was to investigate biological aspects of the species that should be given priority in future studies.

Genetic and environmental factors associated with the risk of cognitive decline and dementia

AD is the most common age related neurodegenerative disease in the industrialized world. Clinically AD is defined as a progressing decline of cognitive functions. Neuropathologically, AD is characterized by the aggregation of b-amyloid (Ab) peptide in the form of extracellular senile plaques, and hyperphosphorlylated tau protein in the form of intracellular neurofibrillary tangles. These neuropathological hallmarks are often accompanied by abundant microvascular damage and pronounced inflammation of the affected brain regions. In this thesis we investigated several aspects of AD focusing on the genetic aspect. We confirmed that Alpha 1 antichymotrypsin (ACT), an acute phase protein, was associated to AD subjects, being plasma levels higher in AD cases than controls. In addition, in a GWA study we demonstrated that two different gene, Clusterin and CR1 were strongly associated to AD. A single gene association not explain such a complex disease like AD. The goal should be to created a network of genetic, phenotypic and clinical data associated to AD. We used a new algorithm, the ANNs, aimed to map variables and search for connectivity among variables. We found specific variables associated to AD like cholesterol levels, the presence of variation in HMGCR enzyme and the age. Other factors such as the BMI, the amount of HDL and blood folate levels were also associated with AD. Pathogen infections, above all viral infections, have been previously associated to AD. The hypothesis suggests that virus and in particular herpes virus could enter the brain when an individual becomes older, perhaps because of a decline in the immune system. Our new hypothesis is that the presence of SNPs in our GWA gene study results in a genetic signature that might affect individual brain susceptibility to infection by herpes virus family during aging.

Functional and Genetic characterization of new genomic islands from an E. coli strain associated with neonatal meningitis.

Enterobacteriaceae genomes evolve through mutations, rearrangements and horizontal gene transfer (HGT). The latter evolutionary pathway works through the acquisition DNA (GEI) modules of foreign origin that enhances fitness of the host to a given environment. The genome of E. coli IHE3034, a strain isolated from a case of neonatal meningitis, has recently been sequenced and its subsequent sequence analysis has predicted 18 possible GEIs, of which: 8 have not been previously described, 5 fully meet the pathogenic island definition and at least 10 that seem to be of prophagic origin. In order to study the GEI distribution of our reference strain, we screened for the presence 18 GEIs a panel of 132 strains, representative of E. coli diversity. Also, using an inverse nested PCR approach we identified 9 GEI that can form an extrachromosomal circular intermediate (CI) and their respective attachment sites (att). Further, we set up a qPCR approach that allowed us to determine the excision rates of 5 genomic islands in different growth conditions. Four islands, specific for strains appertaining to the sequence type complex 95 (STC95), have been deleted in order to assess their function in a Dictyostelium discoideum grazing assays. Overall, the distribution data presented here indicate that 16 IHE3034 GEIs are more associated to the STC95 strains. Also the functional and genetic characterization has uncovered that GEI 13, 17 and 19 are involved in the resistance to phagocitation by Dictyostelium d thus suggesting a possible role in the adaptation of the pathogen during certain stages of infection.

Genetic and environmental factors associated with cardiovascular diseases and acute myocardial infarction

Acute myocardial infarction (AMI) is a multifactorial disease with a complex pathogenesis where lifestyle, individual genetic background and environmental risk factors are involved. Altered inflammatory responses seems to be implicated in the pathogenesis of atherosclerosis. To understand which genes may predispose to increased risk of cardiovascular disease gene polymorphism of immune regulatory genes, and clinical events from the Offs of parents with an early AMI were investigated. Genetics data from Offs were compared with those obtained from healthy subjects and an independent cohort of patients with clinical sporadic AMI. Rates of clinical events during a 24 years follow up from Offs and from an independent Italian population survey were also evaluated. This study showed that a genetic signature consisting of the concomitant presence of the CC genotype of VEGF, the A allele of IL-10 and the A allele of IFN-γ was indeed present in the Offs population. During the 24-year follow-up, Offs with a positive familiarity in spite of a relatively young age showed an increased prevalence of diabetes, ischemic heart disease and stroke. In these patients with the genetic signature the EBV and HHV-6 herpes virus were also investigated and founded. These findings reinforce the notion that subjects with a familial history of AMI are at risk of an accelerated aging of cardiovascular system resulting in cardiovascular events. These data suggest that selected genes with immune regulatory functions and envoronmental factors are part of the complex genetic background contributing to familiarity for cardiovascular diseases.N

Identification and genetic diversity in phytoplasmas associated with diseases of cassava and other agronomic relevant crops in south-east Asia and Latin America

Identification and genetic diversity of phytoplasmas infecting tropical plant species, selected among those most agronomically relevant in South-east Asia and Latin America were studied. Correlation between evolutionary divergence of relevant phytoplasma strains and their geographic distribution by comparison on homologous genes of phytoplasma strains detected in the same or related plant species in other geographical areas worldwide was achieved. Molecular diversity was studied on genes coding ribosomal proteins, groEL, tuf and amp besides phytoplasma 16S rRNA. Selected samples infected by phytoplasmas belonging to diverse ribosomal groups were also studied by in silico RFLP followed by phylogenetic analyses. Moreover a partial genome annotation of a ‘Ca. P. brasiliense’ strain was done towards future application for epidemiological studies. Phytoplasma presence in cassava showing frog skin (CFSD) and witches’ broom (CWB) diseases in Costa Rica - Paraguay and in Vietnam – Thailand, respectively, was evaluated. In both cases, the diseases were associated with phytoplasmas related to aster yellows, apple proliferation and “stolbur” groups, while only phytoplasma related to X-disease group in CFSD, and to hibiscus witches’ broom, elm yellows and clover proliferation groups in CWB. Variability was found among strains belonging to the same ribosomal group but having different geographic origin and associated with different disease. Additionally, a dodder transmission assay to elucidate the role of phytoplasmas in CWB disease was carried out, and resulted in typical phytoplasma symptoms in periwinkle plants associated with the presence of aster yellows-related strains. Lethal wilt disease, a severe disease of oil palm in Colombia that is spreading throughout South America was also studied. Phytoplasmas were detected in symptomatic oil palm and identified as ‘Ca. P. asteris’, ribosomal subgroup 16SrI-B, and were distinguished from other aster yellows phytoplasmas used as reference strains; in particular, from an aster yellows strain infecting corn in the same country.

Factors associated with educational aspirations among adolescents: cues to counteract socioeconomic differences?

Our study aims to follow this effort and to explore the association between health, socioeconomic background, school-related factors, social support and adolescents' sense of coherence and educational aspirations among adolescents from different educational tracks and to contribute to the existing body of knowledge on the role of educational aspirations in the social reproduction of health inequalities. We expect that socioeconomic background will contribute to the development of educational aspirations, but this association will be modified by available social and individual resources, which may be particularly favourable for the group of adolescents who are on lower educational tracks, since for them such resources may lead to gaining a higher educational level.

Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study

Hepatitis C virus (HCV) induces chronic infection in 50% to 80% of infected persons; approximately 50% of these do not respond to therapy. We performed a genome-wide association study to screen for host genetic determinants of HCV persistence and response to therapy.

Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in caucasians

A recent genome-wide study revealed an association between variation in the PNPLA3 gene and liver fat content. In addition, the PNPLA3 single-nucleotide polymorphism rs738409 (M148I) was reported to be associated with advanced alcoholic liver disease in alcohol-dependent individuals of Mestizo descent. We therefore evaluated the impact of rs738409 on the manifestation of alcoholic liver disease in two independent German cohorts. Genotype and allele frequencies of rs738409 (M148I) were determined in 1,043 alcoholic patients with or without alcoholic liver injury and in 376 at-risk drinkers from a population-based cohort. Relative to alcoholic patients without liver damage (n = 439), rs738409 genotype GG was strongly overrepresented in patients with alcoholic liver cirrhosis (n = 210; OR 2.79; P(genotype) = 1.2 × 10(-5) ; P(allelic) = 1.6 × 10(-6) ) and in alcoholic patients without cirrhosis but with elevated alanine aminotransferase levels (n = 219; OR 2.33; P(genotype) = 0.0085; P(allelic) = 0.0042). The latter, biochemically defined association was confirmed in an independent population-based cohort of at-risk drinkers with a median alcohol intake of 300 g/week (OR 4.75; P(genotype) = 0.040; P(allelic) = 0.022), and for aspartate aminotransferase (AST) levels. Frequencies of allele PNPLA3 rs738409(G) in individuals with steatosis and normal alanine aminotransferase (ALT) and AST levels were lower than in alcoholics without steatosis and normal ALT/AST (P(combined) = 0.03). The population attributable risk of cirrhosis in alcoholic carriers of allele PNPLA3 rs738409(G) was estimated at 26.6%. CONCLUSION: Genotype PNPLA3 rs738409(GG) is associated with alcoholic liver cirrhosis and elevated aminotransferase levels in alcoholic Caucasians.

Mapping genetic variants associated with beta-adrenergic responses in inbred mice

β-blockers and β-agonists are primarily used to treat cardiovascular diseases. Inter-individual variability in response to both drug classes is well recognized, yet the identity and relative contribution of the genetic players involved are poorly understood. This work is the first genome-wide association study (GWAS) addressing the values and susceptibility of cardiovascular-related traits to a selective β(1)-blocker, Atenolol (ate), and a β-agonist, Isoproterenol (iso). The phenotypic dataset consisted of 27 highly heritable traits, each measured across 22 inbred mouse strains and four pharmacological conditions. The genotypic panel comprised 79922 informative SNPs of the mouse HapMap resource. Associations were mapped by Efficient Mixed Model Association (EMMA), a method that corrects for the population structure and genetic relatedness of the various strains. A total of 205 separate genome-wide scans were analyzed. The most significant hits include three candidate loci related to cardiac and body weight, three loci for electrocardiographic (ECG) values, two loci for the susceptibility of atrial weight index to iso, four loci for the susceptibility of systolic blood pressure (SBP) to perturbations of the β-adrenergic system, and one locus for the responsiveness of QTc (p<10(-8)). An additional 60 loci were suggestive for one or the other of the 27 traits, while 46 others were suggestive for one or the other drug effects (p<10(-6)). Most hits tagged unexpected regions, yet at least two loci for the susceptibility of SBP to β-adrenergic drugs pointed at members of the hypothalamic-pituitary-thyroid axis. Loci for cardiac-related traits were preferentially enriched in genes expressed in the heart, while 23% of the testable loci were replicated with datasets of the Mouse Phenome Database (MPD). Altogether these data and validation tests indicate that the mapped loci are relevant to the traits and responses studied.

Patterns of regional brain hypometabolism associated with knowledge of semantic features and categories in Alzheimer's disease

The study of semantic memory in patients with Alzheimer's disease (AD) has raised important questions about the representation of conceptual knowledge in the human brain. It is still unknown whether semantic memory impairments are caused by localized damage to specialized regions or by diffuse damage to distributed representations within nonspecialized brain areas. To our knowledge, there have been no direct correlations of neuroimaging of in vivo brain function in AD with performance on tasks differentially addressing visual and functional knowledge of living and nonliving concepts. We used a semantic verification task and resting 18-fluorodeoxyglucose positron emission tomography in a group of mild to moderate AD patients to investigate this issue. The four task conditions required semantic knowledge of (1) visual, (2) functional properties of living objects, and (3) visual or (4) functional properties of nonliving objects. Visual property verification of living objects was significantly correlated with left posterior fusiform gyrus metabolism (Brodmann's area [BA] 37/19). Effects of visual and functional property verification for non-living objects largely overlapped in the left anterior temporal (BA 38/20) and bilateral premotor areas (BA 6), with the visual condition extending more into left lateral precentral areas. There were no associations with functional property verification for living concepts. Our results provide strong support for anatomically separable representations of living and nonliving concepts, as well as visual feature knowledge of living objects, and against distributed accounts of semantic memory that view visual and functional features of living and nonliving objects as distributed across a common set of brain areas.

Genetic testing for TMEM154 mutations associated with lentivirus susceptibility in sheep.

In sheep, small ruminant lentiviruses cause an incurable, progressive, lymphoproliferative disease that affects millions of animals worldwide. Known as ovine progressive pneumonia virus (OPPV) in the U.S., and Visna/Maedi virus (VMV) elsewhere, these viruses reduce an animal's health, productivity, and lifespan. Genetic variation in the ovine transmembrane protein 154 gene (TMEM154) has been previously associated with OPPV infection in U.S. sheep. Sheep with the ancestral TMEM154 haplotype encoding glutamate (E) at position 35, and either form of an N70I variant, were highly-susceptible compared to sheep homozygous for the K35 missense mutation. Our current overall aim was to characterize TMEM154 in sheep from around the world to develop an efficient genetic test for reduced susceptibility. The average frequency of TMEM154 E35 among 74 breeds was 0.51 and indicated that highly-susceptible alleles were present in most breeds around the world. Analysis of whole genome sequences from an international panel of 75 sheep revealed more than 1,300 previously unreported polymorphisms in a 62 kb region containing TMEM154 and confirmed that the most susceptible haplotypes were distributed worldwide. Novel missense mutations were discovered in the signal peptide (A13V) and the extracellular domains (E31Q, I74F, and I102T) of TMEM154. A matrix-assisted laser desorption/ionization-time-of flight mass spectrometry (MALDI-TOF MS) assay was developed to detect these and six previously reported missense and two deletion mutations in TMEM154. In blinded trials, the call rate for the eight most common coding polymorphisms was 99.4% for 499 sheep tested and 96.0% of the animals were assigned paired TMEM154 haplotypes (i.e., diplotypes). The widespread distribution of highly-susceptible TMEM154 alleles suggests that genetic testing and selection may improve the health and productivity of infected flocks.