Project description:Whole blood gene expression profiling from well and malnourished Indian individuals with TB and severely malnourished household contacts with latent TB infection (LTBI). Severe malnutrition was defined as body mass index (BMI) <16. kg/m2 in adults and based on weight-for-height Z scores in children <18 years. Gene expression was measured using RNA-sequencing.
Project description:Associated with numerous metabolic and behavioral abnormalities, obesity is classified by metrics reliant on body weight (such as body mass index). However, overnutrition is the common cause of obesity, and may independently contribute to these obesity-related abnormalities. The goal of this study is to isolate ‘diet/energy balance’ effects independent from ‘body weight’ effects on various metabolic and behavioral parameters using the Diet Switch feeding paradigm in mice. [We conducted] unbiased gene expression analysis of the nutrient-sensing circumventricular hypothalamus [using RNA-seq]. Remarkably, only two genes responded to diet/energy balance (neuropeptide y [npy] and agouti-related peptide [agrp]), while others were related only to body weight. Furthermore, linear regression models revealed that npy and agrp showed similar modifiability by diet/energy balance and body weight compared to electroencephalographic-measured sleep/wake behavior.
Project description:Genome-wide DNA methylation was studied to identify regions with extreme inter-individual variability, half of which show stability within-person, and some of which show covariation with body mass index consistently and are located in or near genes previously implicated in regulating body weight or diabetes.
Project description:The evolutionary and biological bases of the Central African pygmy phenotype, a characteristic of rainforest huntergatherers defined by reduced body size compared with neighboring farmers, remain largely unknown. Here, we perform a joint investigation in Central African hunter-gatherers and farmers of adult standing height, sitting height, leg length, and body mass index (BMI), considering 358 hunter-gatherers and 169 farmers with genotypes for 153,798 SNPs. In addition to reduced standing heights, hunter-gatherers have shorter sitting heights and leg lengths and higher sitting/standing height ratios than farmers and lower BMI for males. Standing height, sitting height, and leg length are strongly correlated with inferred levels of farmer genetic ancestry, whereas BMI is only weakly correlated, perhaps reflecting greater contributions of non-genetic factors to body weight than to height. Single- and multi-marker association tests identify one region and eight genes associated with hunter-gatherer/farmer status, and 24 genes associated with the height-related traits. Many of these genes have putative functions consistent with roles in determining their associated traits and the pygmy phenotype, and they include three associated with standing height in non-Africans (PRKG1, DSCAM, MAGI2). We find evidence that European height-associated SNPs or variants in linkage disequilibrium with them contribute to standing- and sitting-height determination in Central Africans, but not to the differential status of hunter-gatherers and farmers. These findings provide new insights into the biological basis of the pygmy phenotype, and they highlight the potential of cross-population studies for exploring the genetic basis of phenotypes that vary naturally across populations.
Pemberton et al. Human Genetics 2018
https://doi.org/10.1007/s00439-018-1902-3
Project description:Factors predicting body weight gain and associated disturbed glucose metabolism remain to be established. Here we assessed the role of subcutaneous adipocyte lipid mobilization (lipolysis) in spontaneous long-term (>10 years) body weight changes. In two independent clinical cohorts we found that low stimulated lipolysis at baseline correlated inversely with body mass index changes over time. Disturbed lipolysis gave odds ratios of ≥4.6 for weight gain and ≥3.2 for development of insulin resistance and impaired fasting glucose/type 2 diabetes. Baseline adipose mRNA expression of a set of established lipolysis-regulating genes was lower in weight gainers.
Project description:Genome-wide DNA methylation was studied to identify regions with extreme inter-individual variability, half of which show stability within-person, and some of which show covariation with body mass index consistently and are located in or near genes previously implicated in regulating body weight or diabetes. We isolated genomic DNA from non-immortalized lymphocyte samples from participants of the AGES Reykjavik Study and hybridized it to custom-designed NimbleGen microarrays (CHARM arrays).
Project description:Normal and diseased human tissues were profiled for gene expression using the Affymetrix U133 plus 2.0 array In total 677 samples were processed , representing over 90 distinct tissue types Some tissue samples were purchased from Stratagene (SG), Ambion (AB), and Becton-Dickinson (BD) Keywords: Human body index of gene expression Affymetrix human U133 plus 2.0 array was used to transcriptionally profile both normal and diseased human tissues representing over 90 distinct tissue types. This dataset is part of the TransQST collection.