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primary topic: Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease

Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease
type: Article
abstract: It is well established that elevated plasma cholesterol is a major risk factor for atherosclerosis, the cause of cardiovascular disease (CVD), which is most often manifested as coronary artery disease (CAD) and myocardial infarction (MI). The identification through GWAS of genes associated with lipids and CVD has only to a minor extent explained the genetic architecture of CVD and dyslipidemias. In an effort to identify genes affecting cholesterol regulation, an RNAi-based functional profiling of GWAS-derived loci, which were associated with lipid traits, CAD and/or MI was previously performed in our lab (Blattmann et al. 2013). This study resulted in the identification of 55 genes that had an effect on LDL internalization and/ or cellular cholesterol levels. However, most of the screen hits did not have a strong effect, suggesting that the combinatorial -rather than the individual- function of these genes might regulate cholesterol homeostasis and subsequently CVD. This reasoning is supported by the fact that CVD is a complex disease, which is assumed to arise from the synergistic effect of genes. In the present study, a combinatorial RNAi screen was performed in order to identify interactions between genes identified in the aforementioned study, after juxtaposing them with the results of an Exome Chip of more than 70,000 individuals, genotyped for lipid traits (LDL, HDL, TG, TC) (Peloso et al. 2014). For this purpose, the effect on LDL uptake of all pairwise combinations between 30 candidate genes was tested, and 21 pairs were confirmed as genetic interactors. A gene interaction model network was constructed, based on the results of the screen, connecting known cholesterol regulators, as well as genes without a previously reported lipidregulatory function. Secondary screens were performed to measure the effect of the gene interactions on LDLR mRNA and protein, as well as on SREBF1 and SREBF2 mRNA levels. The results from secondary experiments provided further valu…
date: 2018
author list: authors
type: EPrint
type: DoctoralThesisEPrint
is part of: repository
has document: Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease (Other)
has document: Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease (PDF)
subject: 570 Biowissenschaften, Biologie

Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease (PDF)
type: Document
has file: Anthi Trasta_PhD Thesis.pdf
has part: Anthi Trasta_PhD Thesis.pdf

Anthi Trasta
type: Person
given name: Anthi
family name: Trasta

Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease (Other)
type: Document
is version of: Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease (PDF)
is volatile version of: Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease (PDF)
ispreview thumbnail version of: Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease (PDF)

Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease (Other)
type: Document
is version of: Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease (PDF)
is volatile version of: Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease (PDF)
ismedium thumbnail version of: Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease (PDF)

Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease (Other)
type: Document
is version of: Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease (PDF)
is volatile version of: Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease (PDF)
issmall thumbnail version of: Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease (PDF)

Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease (Other)
type: Document
is version of: Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease (PDF)
is volatile version of: Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease (PDF)
is index codes version of: Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease (PDF)

Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease (Other)
type: Document
is version of: Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease (PDF)
is volatile version of: Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease (PDF)
islightbox thumbnail version of: Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease (PDF)

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primary topic: Unraveling Gene Networks of Human Cholesterol Homeostasis and Their Roles in Cardiovascular Disease

570 Biowissenschaften, Biologie
type: Concept
preferred label: 570 Life sciences @en