The genome sequencing of H37Rv strain of Mycobacterium tuberculosis was completed in 1998 followed by the whole genome sequencing of a clinical isolate, CDC1551 in 2002. Since then, the genomic sequences of a number of other strains have become available making it one of the better studied pathogenic bacterial species at the genomic level. However, annotation of its genome remains challenging because of high GC content and dissimilarity to other model prokaryotes. To this end, we carried out an in-depth proteogenomic analysis of the M. tuberculosis H37Rv strain using Fourier transform mass spectrometry with high resolution at both MS and tandem MS levels. In all, we identified 3176 proteins from Mycobacterium tuberculosis representing ϳ80% of its total predicted gene count. In addition to protein database search, we carried out a genome database search, which led to identification of ϳ250 novel peptides. Based on these novel genome search-specific peptides, we discovered 41 novel protein coding genes in the H37Rv genome. Using peptide evidence and alternative gene prediction tools, we also corrected 79 gene models. Finally, mass spectrometric data from N terminus-derived peptides confirmed 727 existing annotations for translational start sites while correcting those for 33 proteins. We report creation of a high confidence set of protein coding regions in Mycobacterium tuberculosis genome obtained by high resolution tandem mass-spectrometry at both precursor and fragment detection steps for the first time. This proteogenomic approach should be generally applicable to other organisms whose genomes have already been sequenced for obtaining a more accurate catalogue of protein-coding genes.
Candidate gene and genome-wide association studies have not identified common variants, which are reliably associated with depression. The recent identification of obesity predisposing genes that are highly expressed in the brain raises the possibility of their genetic contribution to depression. As variation in the intron 1 of the fat mass- and obesity-associated (FTO) gene contributes to polygenic obesity, we assessed the possibility that FTO gene may contribute to depression in a cross-sectional multi-ethnic sample of 6561 depression cases and 21,932 controls selected from the EpiDREAM, INTERHEART, DeCC (depression case-control study) and Cohorte Lausannoise (CoLaus) studies. Major depression was defined according to DSM IV diagnostic criteria. Association analyses were performed under the additive genetic model. A meta-analysis of the four studies showed a significant inverse association between the obesity risk FTO rs9939609 A variant and depression (odds ratio=0.92 (0.89, 0.97), P=3 × 10(-4)) adjusted for age, sex, ethnicity/population structure and body-mass index (BMI) with no significant between-study heterogeneity (I(2)=0%, P=0.63). The FTO rs9939609 A variant was also associated with increased BMI in the four studies (β 0.30 (0.08, 0.51), P=0.0064) adjusted for age, sex and ethnicity/population structure. In conclusion, we provide the first evidence that the FTO rs9939609 A variant may be associated with a lower risk of depression independently of its effect on BMI. This study highlights the potential importance of obesity predisposing genes on depression.
In this large multiethnic cohort, the risk of CV events or death increased progressively among individuals who were normoglycaemic, IFG or IGT, and newly diagnosed diabetics. A 1 mmol/l increase in FPG was associated with a 17% increase in the risk of future CV events or death. Therapeutic or behavioural interventions designed to either prevent glucose levels from rising, or lower glucose among individuals with dysglycaemia should be evaluated.
Objective. Cardiovascular disease (CVD) and cancer are the two leading causes of death in the United States; at the same time, the number of survivors is increasing as therapies continue to improve. The primary objective of this study is to determine the prevalence and characteristics of individuals affected by both CVD and cancer.Design and setting. We conducted a prevalence study using the 2009 and 2010 national Behavioural Risk Factor Surveillance System population survey. Data from a random sample of individuals (aged 25-99 years) from all states were collected. All participants provided information regarding their CVD and cancer status. Multivariable regression identified associations between participants' characteristics and the prevalence of double disease burden.Results. Amongst 442 964 study participants, the overall prevalence rates were 11% for CVD and 15% for cancer; 3% of participants reported being survivors of both CVD and cancer. The prevalence of CVD+cancer increased twofold by 65 years of age (odds ratio [OR] 2.4, 95% confidence interval [CI] 2.3-2.5) and doubled again at ≥75 years (OR 4.9, 95% CI 4.6-5.1) and was higher amongst men (OR 1.6, 95% CI 1.6-1.7), multiracial individuals (OR 1.8, 95% CI 1.5-2.0) and those without a high school diploma (OR 1.3, 95% CI 1.2-1.4). Amongst individuals with CVD, 25% also reported having cancer, whilst 19% of all cancer survivors reported having CVD.Conclusions. The prevalence of the double burden of disease increased with age; this is particularly important as the 'baby boomers' reach this highrisk age group. Future studies should explore potential common upstream or downstream mechanisms of CVD and cancer as well as public health strategies to cope with the double burden of disease.
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