Model organisms contribute to diagnosis and discovery in the undiagnosed diseases network: current state and a future vision.

Orphanet Journal of Rare Diseases
Dustin BaldridgeMonte Westerfield

Abstract

Decreased sequencing costs have led to an explosion of genetic and genomic data. These data have revealed thousands of candidate human disease variants. Establishing which variants cause phenotypes and diseases, however, has remained challenging. Significant progress has been made, including advances by the National Institutes of Health (NIH)-funded Undiagnosed Diseases Network (UDN). However, 6000-13,000 additional disease genes remain to be identified. The continued discovery of rare diseases and their genetic underpinnings provides benefits to affected patients, of whom there are more than 400 million worldwide, and also advances understanding the mechanisms of more common diseases. Platforms employing model organisms enable discovery of novel gene-disease relationships, help establish variant pathogenicity, and often lead to the exploration of underlying mechanisms of pathophysiology that suggest new therapies. The Model Organism Screening Center (MOSC) of the UDN is a unique resource dedicated to utilizing informatics and functional studies in model organisms, including worm (Caenorhabditis elegans), fly (Drosophila melanogaster), and zebrafish (Danio rerio), to aid in diagnosis. The MOSC has directly contributed to the di...Continue Reading

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Citations

Jun 29, 2021·Journal of Toxicology and Environmental Health. Part a·Thaís Teixeira da SilvaFrancielle Alline Martins
Aug 3, 2021·Trends in Genetics : TIG·Emily A BeckJohn H Postlethwait
Nov 7, 2021·Mammalian Genome : Official Journal of the International Mammalian Genome Society·M L KaldunskiA E Kwitek

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Software Mentioned

MARRVEL
Orphanet
Matchmaker Exchange
gnomAD
Online Mendelian Inheritance in Man ( OMIM )

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