Send to

Choose Destination
Hum Mol Genet. 2019 Jun 22. pii: ddz135. doi: 10.1093/hmg/ddz135. [Epub ahead of print]

The fruit fly at the interface of diagnosis and pathogenic mechanisms of rare and common human diseases.

Bellen HJ1,2,3,4,5, Wangler MF1,3,4, Yamamoto S1,2,3,4.

Author information

Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Houston, TX 77030, USA.
Department of Neuroscience, BCM, Houston, TX 77030, USA.
Program in Developmental Biology, BCM, Houston, TX 77030, USA.
Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA.
Howard Hughes Medical Institute, Houston, TX 77030, USA.


Drosophila melanogaster is a unique, powerful genetic model organism for studying a broad range of biological questions. Human studies that probe the genetic causes of rare and undiagnosed diseases using massive-parallel sequencing often require complementary gene function studies to determine if and how rare variants affect gene function. These studies also provide inroads to disease mechanisms and therapeutic targets. In this review we discuss strategies for functional studies of rare human variants in Drosophila. We focus on our experience in establishing a Drosophila Core for the Model Organisms Screening Center (MOSC) for the Undiagnosed Diseases Network (UDN) and concurrent fly studies with other large genomic rare disease research efforts such as the Centers for Mendelian Genomics (CMG). We outline four major strategies that use the latest technology in fly genetics to understand the impact of human variants on gene function. We also mention general concepts in probing disease mechanisms, therapeutics and using rare disease to understand common diseases. Drosophila is and will continue to be a fundamental genetic model to identify new disease-causing variants, pathogenic mechanisms and drugs that will impact medicine.


Drosophila melanogaster ; Centers for Mendelian Genomics; Rare and Undiagnosed Diseases; Undiagnosed Diseases Network; Variants of Uncertain Significance (VUS)


Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center