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Genetics. 2017 Sep;207(1):9-27. doi: 10.1534/genetics.117.203067.

Model Organisms Facilitate Rare Disease Diagnosis and Therapeutic Research.

Author information

1
Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, Texas 77030.
2
Department of Pediatrics, Baylor College of Medicine (BCM), Houston, Texas 77030.
3
Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas 77030.
4
Program in Developmental Biology, Baylor College of Medicine (BCM), Houston, Texas 77030.
5
Department of Neuroscience, Baylor College of Medicine (BCM), Houston, Texas 77030.
6
Department of Pediatrics, Section of Child Neurology, Baylor College of Medicine (BCM), Houston, Texas 77030.
7
Institute of Neuroscience, University of Oregon, Eugene, Oregon 97403.
8
Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia V6T 1Z4C, Canada.
9
Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ontario K1H 8L1, Canada.
10
Department of Pediatrics, University of Montreal, Quebec H3T 1C5, Canada.
11
Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, Texas 77030 hbellen@bcm.edu.
12
Howard Hughes Medical Institute, Baylor College of Medicine (BCM), Houston, Texas 77030.

Abstract

Efforts to identify the genetic underpinnings of rare undiagnosed diseases increasingly involve the use of next-generation sequencing and comparative genomic hybridization methods. These efforts are limited by a lack of knowledge regarding gene function, and an inability to predict the impact of genetic variation on the encoded protein function. Diagnostic challenges posed by undiagnosed diseases have solutions in model organism research, which provides a wealth of detailed biological information. Model organism geneticists are by necessity experts in particular genes, gene families, specific organs, and biological functions. Here, we review the current state of research into undiagnosed diseases, highlighting large efforts in North America and internationally, including the Undiagnosed Diseases Network (UDN) (Supplemental Material, File S1) and UDN International (UDNI), the Centers for Mendelian Genomics (CMG), and the Canadian Rare Diseases Models and Mechanisms Network (RDMM). We discuss how merging human genetics with model organism research guides experimental studies to solve these medical mysteries, gain new insights into disease pathogenesis, and uncover new therapeutic strategies.

KEYWORDS:

Drosophila; diagnostics; functional genomics; genetic diseases; human; whole-exome sequencing; zebrafish

PMID:
28874452
PMCID:
PMC5586389
DOI:
10.1534/genetics.117.203067
[Indexed for MEDLINE]
Free PMC Article

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