Cis- and Trans-Modifiers of Repeat Expansions: Blending Model Systems with Human Genetics.

Trends Genet

Department of Biology, Tufts University, Medford, MA 02155, USA. Electronic address:

Published: June 2018

AI Article Synopsis

  • * Genetic variants can influence these diseases both nearby (cis) and far (trans) from the repeat regions, but our understanding is limited by discrepancies between model studies and human genetic diversity.
  • * The authors suggest using SNP-based screening in model systems to better identify and understand genetic modifiers that can impact these diseases and improve patient care.

Article Abstract

Over 30 hereditary diseases are caused by the expansion of microsatellite repeats. The length of the expandable repeat is the main hereditary determinant of these disorders. They are also affected by numerous genomic variants that are either nearby (cis) or physically separated from (trans) the repetitive locus, which we review here. These genetic variants have largely been elucidated in model systems using gene knockouts, while a few have been directly observed as single-nucleotide polymorphisms (SNPs) in patients. There is a notable disconnect between these two bodies of knowledge: knockouts poorly approximate the SNP-level variation in human populations that gives rise to medically relevant cis- and trans-modifiers, while the rarity of these diseases limits the statistical power of SNP-based analysis in humans. We propose that high-throughput SNP-based screening in model systems could become a useful approach to quickly identify and characterize modifiers of clinical relevance for patients.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959756PMC
http://dx.doi.org/10.1016/j.tig.2018.02.005DOI Listing

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