منابع مشابه
LIPA Variants in Genome-Wide Association Studies of Coronary Artery Diseases: Loss-of-Function or Gain-of-Function?
Genome-wide association studies (GWASs) have identified multiple coronary artery disease (CAD) risk loci, yet moving from association to mechanistic insights and therapeutic translation remains a major challenge. Several GWASs have identified LIPA as a novel locus for CAD. LIPA encodes lysosomal acid lipase (LAL), the major lysosomal enzyme hydrolyzing cholesteryl esters (CEs) and triglycerides...
متن کاملWhen loss-of-function is loss of function: assessing mutational signatures and impact of loss-of-function genetic variants
Motivation Loss-of-function genetic variants are frequently associated with severe clinical phenotypes, yet many are present in the genomes of healthy individuals. The available methods to assess the impact of these variants rely primarily upon evolutionary conservation with little to no consideration of the structural and functional implications for the protein. They further do not provide inf...
متن کاملGain- and loss-of-function in chick embryos by electroporation
It remained very difficult to manipulate gene expression in chick embryos until the advent of in ovo electroporation which enabled the induction of both gain-of-function, and recently loss-of-function, of a gene of interest at a specific developmental stage. Gain-of-function by electroporation is so effective that it has become widely adopted in developmental studies in the chick. Recently, it ...
متن کاملMolecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote.
Elevated levels of circulating low-density lipoprotein cholesterol (LDL-C) play a central role in the development of atherosclerosis. Mutations in proprotein convertase subtilisin/kexin type 9 (PCSK9) that are associated with lower plasma levels of LDL-C confer protection from coronary heart disease. Here, we show that four severe loss-of-function mutations prevent the secretion of PCSK9 by dis...
متن کاملABCA7 loss-of-function variants, expression, and neurologic disease risk
OBJECTIVE To investigate and characterize putative "loss-of-function" (LOF) adenosine triphosphate-binding cassette, subfamily A member 7 (ABCA7) mutations reported to associate with Alzheimer disease (AD) risk. METHODS We genotyped 6 previously reported ABCA7 putative LOF variants in 1,465 participants with AD, 381 participants with other neuropathologies (non-AD), and 1,043 controls and ass...
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ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 2012
ISSN: 0021-9258
DOI: 10.1074/jbc.m112.399725