Genetic modifiers of age-at-onset in polyglutamine diseases.

Genetic modifiers of age-at-onset in polyglutamine diseases.
Ageing Res Rev. 2018 Oct 21;:
Authors: Chen Z, Sequeiros J, Tang B, Jiang H
Abstract
Polyglutamine (polyQ) diseases are a group of clinically and genetically heterogeneous neurodegenerative diseases. Expansion size correlates with age-at-onset (AO) and severity, and shows a critical threshold for each polyQ disease. Although an expanded CAG tract is sufficient to trigger disease, not all variation in AO is explained by (CAG)n length, which suggests the contribution of other modifying factors. Methods used to identify genetic modifiers in polyQ diseases have progressed from candidate genes to unbiased genome-wide searches. Inconsistency of results from candidate-genes studies are partly explained by sample size, study design and variable population frequency of "polymorphisms"; a genome-wide search may help elucidating more precise disease mechanisms underlying specific interaction networks. We review known genetic modifiers for polyQ diseases, and discuss developing strategies to find modulation, from common variants to networks disclosing small cumulative effects of key genes and modifying pathways. This may lead to a better understanding of genotype-phenotype correlation and the proposal of new potential targets for therapeutical interventions.
PMID: 30355507 [PubMed - as supplied by publisher]

Source: Ageing Research Reviews - October 21, 2018 Category: Genetics & Stem Cells Authors: Chen Z, Sequeiros J, Tang B, Jiang H Tags: Ageing Res Rev Source Type: research