Suggestion for linkage of chromosome 1p35.2 and 3q28 to plasma adiponectin concentrations in the GOLDN Study

<p>Abstract</p> <p>Background</p> <p>Adiponectin is inversely associated with obesity, insulin resistance, and atherosclerosis, but little is known about the genetic pathways that regulate the plasma level of this protein. To find novel genes that influence circulating levels of adiponectin, a genome-wide linkage scan was performed on plasma adiponectin concentrations before and after 3 weeks of treatment with fenofibrate (160 mg daily) in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. We studied Caucasian individuals (n = 1121) from 190 families in Utah and Minnesota. Of these, 859 individuals from 175 families had both baseline and post-fenofibrate treatment measurements for adiponectin. Plasma adiponectin concentrations were measured with an ELISA assay. All participants were typed for microsatellite markers included in the Marshfield Mammalian Genotyping Service marker set 12, which includes 407 markers spaced at approximately 10 cM regions across the genome. Variance components analysis was used to estimate heritability and to perform genome-wide scans. Adiponectin was adjusted for age, sex, and field center. Additional models also included BMI adjustment.</p> <p>Results</p> <p>Baseline and post-fenofibrate adiponectin measurements were highly correlated (r = 0.95). Suggestive (LOD > 2) peaks were found on chromosomes 1p35.2 and 3q28 (near the location of the adiponectin gene).</p> <p>Conclusion</p> <p>Two candidate genes, <it>IL22RA1 </it>and <it>IL28RA</it>, lie under the chromosome 1 peak; further analyses are needed to identify the specific genetic variants in this region that influence circulating adiponectin concentrations.</p

Low HDL Cholesterol, Smoking and IL-13 R130Q Polymorphism are Associated with Myocardial Infarction in Greek Cypriot Males. A Pilot Study

This study was carried out in Greek Cypriot males to identify risk factors that predispose to myocardial infarction (MI). Genetic and lipid risk factors were investigated for the first time in a Greek Cypriot male case-control study.Contrary to other studies, mean low density lipoprotein cholesterol did not differ between cases and controls. High density lipoprotein cholesterol on the other hand, although within normal range in cases and controls, was significantly higher in the control population. In agreement with many other studies, smoking was significantly more prevalent in cases compared with controls. In pooled cases and controls, smokers had a significantly lower HDL-C level compared with non-smokers. The frequency of the IL-13 R130Q homozygotes for the mutation (QQ), as well as the mutant allele were significantly higher in cases compared with controls. The IL-13 R130Q variant, or another locus, linked to it, may increase the risk of MI

Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration

Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.</p

The proteome of dissimilatory metal-reducing microorganism Geobacter sulfurreducens under various growth conditions

The proteome of Geobacter sulfurreducens, a model for the Geobacter species that predominate in many Fe(III)-reducing subsurface environments, was characterized with ultra high-pressure liquid chromatography and mass spectrometry using accurate mass and time (AMT) tags as well as with more traditional two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). Cells were grown under six different growth conditions in order to enhance the potential that a wide range of genes would be expressed. The AMT tag approach was able to identify a much greater number of proteins than could be detected with the 2-D PAGE approach. With the AMT approach over 3,000 gene products were identified, representing about 90% of the total predicted gene products in the genome. A high proportion of predicted proteins in most protein role categories were detected; the highest number of proteins was identified in the hypothetical protein role category. Furthermore, 91 c-type cytochromes of 111 predicted genes in the G. sulfurreducens genome were identified. Differences in the abundance of cytochromes and other proteins under different growth conditions provided information for future functional analysis of these proteins. These results demonstrate that a high percentage of the predicted proteins in the G. sulfurreducens genome are produced and that the AMT tag approach provides a rapid method for comparing differential expression of proteins under different growth conditions in this organism

TM4SF20 ancestral deletion and susceptibility to a pediatric disorder of early language delay and cerebral white matter hyperintensities

White matter hyperintensities (WMHs) of the brain are important markers of aging and small-vessel disease. WMHs are rare in healthy children and, when observed, often occur with comorbid neuroinflammatory or vasculitic processes. Here, we describe a complex 4 kb deletion in 2q36.3 that segregates with early childhood communication disorders and WMH in 15 unrelated families predominantly from Southeast Asia. The premature brain aging phenotype with punctate and multifocal WMHs was observed in ∼70% of young carrier parents who underwent brain MRI. The complex deletion removes the penultimate exon 3 of TM4SF20, a gene encoding a transmembrane protein of unknown function. Minigene analysis showed that the resultant net loss of an exon introduces a premature stop codon, which, in turn, leads to the generation of a stable protein that fails to target to the plasma membrane and accumulates in the cytoplasm. Finally, we report this deletion to be enriched in individuals of Vietnamese Kinh descent, with an allele frequency of about 1%, embedded in an ancestral haplotype. Our data point to a constellation of early language delay and WMH phenotypes, driven by a likely toxic mechanism of TM4SF20 truncation, and highlight the importance of understanding and managing population-specific low-frequency pathogenic alleles.</p