How Surrogate and Chemical Genetics in Model Organisms Can Suggest Therapies for Human Genetic Diseases

• Published in: Genetics (Austin) Vol. 208; no. 3; pp. 833 - 851
• Main Authors: Strynatka, Katherine A, Gurrola-Gal, Michelle C, Berman, Jason N, McMaster, Christopher R
• Format: Journal Article
• Language: English
• Published: United States Genetics Society of America 01-03-2018
• Subjects: Animals; Biomarkers; Cancer therapies; Danio rerio; Disease; Disease Models, Animal; Diseases; Gene sequencing; Genes; Genetic Association Studies - methods; Genetic Diseases, Inborn - diagnosis; Genetic Diseases, Inborn - genetics; Genetic Diseases, Inborn - therapy; Genetic disorders; Genetic Predisposition to Disease; Genetics; Genome-Wide Association Study; Genomes; Genotype & phenotype; Humans; Medical treatment; Mutation; Neoplasms - diagnosis; Neoplasms - genetics; Neoplasms - therapy; Neuroblastoma; Organisms; Patients; Phenotype; Phenotypes; Researchers; Review; Therapeutic applications; Xenograft Model Antitumor Assays; Yeast; Yeasts; Zebrafish; Canada; United States > US; orphan disease; drug discovery; model organism; chemical genetics; cancer; zebrafish; genetic disease; yeast
• ISSN: 1943-2631; 0016-6731; 1943-2631
• DOI: 10.1534/genetics.117.300124

Genetic diseases are both inherited and acquired. Many genetic diseases fall under the paradigm of orphan diseases, a disease found in < 1 in 2000 persons. With rapid and cost-effective genome sequencing becoming the norm, many causal mutations for genetic diseases are being rapidly determined. In this regard, model organisms are playing an important role in validating if specific mutations identified in patients drive the observed phenotype. An emerging challenge for model organism researchers is the application of genetic and chemical genetic platforms to discover drug targets and drugs/drug-like molecules for potential treatment options for patients with genetic disease. This review provides an overview of how model organisms have contributed to our understanding of genetic disease, with a focus on the roles of yeast and zebrafish in gene discovery and the identification of compounds that could potentially treat human genetic diseases.