Overview

The Model Organisms Screening Center (MOSC) for the Undiagnosed Diseases Network (UDN) is a collaborative center with investigators from Baylor College of Medicine (BCM) and University of Oregon (UO). The MOSC allows for world-renowned experts in Drosophila (fruit fly) and Zebrafish genetics and biology to tackle undiagnosed diseases. By combining the state-of-the-art genetic and genomic technologies, the MOSC investigates whether a rare variant identified in UDN patient genomes may contribute to disease pathogenesis. The overall MOSC is led by the Principal Investigator (PI) Hugo J. Bellen, DVM, PhD (BCM). The Drosophila Core is led by Co-PIs Michael F. Wangler, MD, and Shinya Yamamoto, DVM, PhD (BCM). The Zebrafish Core is led by Co-PIs Monte Westerfield, PhD, and John Postlethwait, PhD (UO).

Why Drosophila and Zebrafish?

Over the past century, genetic model organisms have taught us so much about human biology and disease mechanisms. Although these organisms (e.g. yeast, nematode worm, fly, zebrafish, mouse) may look very different from us, fundamental biological mechanisms and genes are well conserved throughout evolution. To investigate hundreds of rare variants found through sequencing UDN patients’ and their family members’ genomes, the MOSC uses two model organisms, fruit fly (Drosophila melanogaster) and Zebrafish. These animals are cost efficient, have short life-cycles and amenable to sophisticated genetic manipulations to “model” a human disease condition. Flies and Zebrafish are complementary to one another, providing a synergism. Candidate genes and variants that are shown to be functional can be further pursued in mammalian model systems such as the mouse for further translational studies.

UDNMOSC_Web_Fig1

MOSC Workflow

When a diagnosis is not reached after performing a thorough clinical, genetic and/or metabolomic workup, the UDN Clinical Sites submit candidate gene(s)/variant(s) to the MOSC together with a brief description of the patient’s condition. The MOSC first performs a database search using the MARRVEL tool to aggregate existing information on the human gene/variant and its model organism orthologs. In addition, matchmaking with patients in other disease cohorts are attempted through collaborations to identify other individuals with similar genotype and phenotype. Once a variant is considered to be a high priority candidate, experiments to assess gene and variant function are designed by MOSC investigators and are pursued in the Drosophila Core or in the Zebrafish Core.

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MOSC Publications

Research Articles

A Syndromic Neurodevelopmental Disorder Caused by De Novo Variants in EBF3
The American Journal of Human Genetics (AJHG)

A Recurrent De Novo Variant in NACC1 Causes a Syndrome Characterized by Infantile Epilepsy, Cataracts, and Profound Developmental Delay
The American Journal of Human Genetics (AJHG)

Review Articles

Fruit flies in biomedical research.
Genetics

Morgan’s legacy: fruit flies and the functional annotation of conserved genes.
Cell

Bedside Back to Bench: Building Bridges between Basic and Clinical Genomic Research.
Cell

RFA

RFA-RM-14-016

Grant

1U54NS093793-01

MOSC Photos