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Early progression to active tuberculosis is a highly heritable trait driven by 3q23 in Peruvians

ABSTRACT: Early progression to active tuberculosis is a highly heritable trait driven by 3q23 in Peruvians

PROVIDER: PRJNA630782 | ENA |

REPOSITORIES: ENA

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Early progression to active tuberculosis is a highly heritable trait driven by 3q23 in Peruvians

Project description:Early progression to active tuberculosis is a highly heritable trait driven by 3q23 in Peruvians

| PRJNA630783 | ENA

Early progression to active tuberculosis is a highly heritable trait driven by 3q23 in Peruvians.

Project description:Of the 1.8 billion people worldwide infected with Mycobacterium tuberculosis, 5-15% will develop active tuberculosis (TB). Approximately half will progress to active TB within the first 18 months after infection, presumably because they fail to mount an effective initial immune response. Here, in a genome-wide genetic study of early TB progression, we genotype 4002 active TB cases and their household contacts in Peru. We quantify genetic heritability ([Formula: see text]) of early TB progression to be 21.2% (standard error 0.08). This suggests TB progression has a strong genetic basis, and is comparable to traits with well-established genetic bases. We identify a novel association between early TB progression and variants located in a putative enhancer region on chromosome 3q23 (rs73226617, OR = 1.18; P = 3.93 × 10-8). With in silico and in vitro analyses we identify rs73226617 or rs148722713 as the likely functional variant and ATP1B3 as a potential causal target gene with monocyte specific function.

| S-EPMC6704092 | biostudies-literature

Heritable fetal protection against MLL::ENL-driven leukemogenesis depends on MLL3

Project description:Heritable fetal protection against MLL::ENL-driven leukemogenesis depends on MLL3

| PRJNA1231439 | ENA

Heritable fetal protection against MLL::ENL-driven leukemogenesis depends on MLL3 [scRNA-seq]

Project description:Heritable fetal protection against MLL::ENL-driven leukemogenesis depends on MLL3 [scRNA-seq]

| PRJNA1231436 | ENA

Heritable fetal protection against MLL::ENL-driven leukemogenesis depends on MLL3 [scATAC-seq]

Project description:Heritable fetal protection against MLL::ENL-driven leukemogenesis depends on MLL3 [scATAC-seq]

| PRJNA1231437 | ENA

Trait tacking for predictive evolution of metabolic pheotypes

Project description:Adaptive laboratory evolution is highly effective for improving desired traits through natural selection. However, its applicability is inherently constrained to growth-correlated traits precluding traits of interest that incur a fitness cost, such as metabolite secretion. Here, we introduce the concept of tacking trait enabling naturalÂ selection of fitness-costly metabolic traits. The concept is inspired from the tacking maneuver used in sailing for traversing upwind.Â We use first-principle metabolic models to design an evolution niche wherein the tacking trait and fitness become correlated. Adaptive evolution in this niche, when followed by the reversal to the original niche, manifests in the improvement of the desired trait due to biochemical coupling between the tacking and the desired trait. We experimentally demonstrate this strategy, termed EvolveX, by evolving wine yeasts for increased aroma production. Our results pave the way for precision laboratory evolution for biotechnological and ecological applications.

2022-07-12 | PXD023171 | Pride

Low abundant but highly transcriptionally active uncharacterised Nitrosomonas sp. drives ammonia-oxidation in the Brouage mudflat, France.

Project description:Low abundant but highly active Nitrosomonas sp.

| PRJEB72740 | ENA

Heritable fetal protection against MLL::ENL-driven leukemogenesis depends on MLL3 [Bulk RNA-seq]

Project description:Heritable fetal protection against MLL::ENL-driven leukemogenesis depends on MLL3 [Bulk RNA-seq]

| PRJNA1231447 | ENA

Insulin clearance: confirmation as a highly heritable trait, and genome-wide linkage analysis.

Project description:Aims/hypothesisWe have previously documented a high heritability of insulin clearance in a Hispanic cohort. Here, our goal was to confirm the high heritability in a second cohort and search for genetic loci contributing to insulin clearance.MethodsHyperinsulinaemic-euglycaemic clamps were performed in 513 participants from 140 Hispanic families. Heritability was estimated for clamp-derived insulin clearance and a two-phase genome-wide linkage scan was conducted using a variance components approach. Linkage peaks were further investigated by candidate gene association analysis in two cohorts.ResultsThe covariate-adjusted heritability of insulin clearance was 73%, indicating that the majority of the phenotypic variance is due to genetic factors. In the Phase 1 linkage scan, no signals with a logarithm of odds (LOD) score >2 were detected. In the Phase 2 scan, two linkage peaks with an LOD >2 for insulin clearance were identified on chromosomes 15 (LOD 3.62) and 20 (LOD 2.43). These loci harbour several promising candidate genes for insulin clearance, with 12 single nucleotide polymorphisms (SNPs) on chromosome 15 and six SNPs on chromosome 20 being associated with insulin clearance in both Hispanic cohorts.Conclusions/interpretationIn a second Hispanic cohort, we confirmed that insulin clearance is a highly heritable trait and identified chromosomal loci that harbour genes regulating insulin clearance. The identification of such genes may improve our understanding of how the body clears insulin, thus leading to improved risk assessment, diagnosis, prevention and therapy of diabetes, as well as of other hyperinsulinaemic disorders, such as the metabolic syndrome and polycystic ovary syndrome.

| S-EPMC3391346 | biostudies-literature

Low-abundant but highly transcriptionally active uncharacterised Nitrosomonas sp. drive ammonia-oxidation in the Brouage mudflat, France.

Project description:Low abundant but highly active Nitrosomonas sp. drive nitrification

| PRJEB72861 | ENA