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Human Genomics

, 11:12

First Online: 25 May 2017Received: 09 March 2017Accepted: 12 May 2017DOI: 10.1186-s40246-017-0108-4

Cite this article as: Wang, Y.A., Kammenga, J.E. & Harvey, S.C. Hum Genomics 2017 11: 12. doi:10.1186-s40246-017-0108-4

Abstract

BackgroundNeurodegenerative diseases NGDs such as Alzheimer’s and Parkinson’s are debilitating and largely untreatable conditions strongly linked to age. The clinical, neuropathological, and genetic components of NGDs indicate that neurodegeneration is a complex trait determined by multiple genes and by the environment.

Main bodyThe symptoms of NGDs differ among individuals due to their genetic background, and this variation affects the onset and progression of NGD and NGD-like states. Such genetic variation affects the molecular and cellular processes underlying NGDs, leading to differential clinical phenotypes. So far, we have a limited understanding of the mechanisms of individual background variation. Here, we consider how variation between genetic backgrounds affects the mechanisms of aging and proteostasis in NGD phenotypes. We discuss how the nematode Caenorhabditis elegans can be used to identify the role of variation between genetic backgrounds. Additionally, we review advances in C. elegans methods that can facilitate the identification of NGD regulators and-or networks.

ConclusionGenetic variation both in disease genes and in regulatory factors that modulate onset and progression of NGDs are incompletely understood. The nematode C. elegans represents a valuable system in which to address such questions.

KeywordsNeurodegenerative diseases Natural variation Quantitative genetics C. elegans Abbreviations5-HIAASerotoninmetabolite 5 hydroxyindoleacetic acid

ADAlzheimer’s disease

ALSAmyotrophic lateral sclerosis

APPAmyloid precursor protein

AβBeta amyloid peptide

BDNFBrain-derived neurotrophic factor

CGVsCryptic genetic variations

CNVCopy number variants

eQTLsExpression quantitative trait loci

EREndoplasmic reticulum

FOXOForkhead box O protein

FTDFrontotemporal dementia

GWASGenome wide association studies

HDHuntington’s disease

HTTHuntingtin

IISInsulin-insulin-like growth factor

ILsIntrogression lines

JNKc-Jun N-terminal kinase

LOADLate-onset Alzheimer’s disease

LRRK2Leucine-rich repeat kinase 2

MAOAMonogeamine oxidase amx-2

MAPKMitogen-activated protein kinases

MLH1MutL homolog 1

mROSMitochondrial reactive oxygen species

mTORMechanistic target of rapamycin

mTORC2Mammalian TORC2

NGDsNeurodegenerative diseases

PCDProgrammed cell death

PDParkinson’s disease

polyQPolyglutamine

PrDPrion diseases

QTLsQuantitative trait locus

QTNsQuantitative trait nucleotides

RILsRecombinant inbred lines

ROSReactive oxygen species

S6KSubunit S6 kinase

SNPSingle nucleotide polymorphism

UPRUnfolded protein response

UPSUbiquitin-proteasome system

WESWhole-exome sequencing





Autor: Yiru Anning Wang - Jan Edward Kammenga - Simon Crawford Harvey

Fuente: https://link.springer.com/







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