MSCI815 Module 6


Analysis of human disease genes in Drosophila.


Lawrence T. Reiter, Ph.D.

Department of Neurology

May 8th, 2008


The purpose of this module is to introduce the concept of cross species database searches to identify appropriate genetic model systems for the study of human disease genes.  We will discuss several entry points into the identification of homologues to human diseases genes, how to search human disease databases and also how to search several Drosophila specific databases to identify reagents and information on a particular homologue.


Genetic Model Organisms in the lab:





Similarity to Human Genome



Organisms per

Genetic Screen






1 cell


2 hours




959 cells


3 days




>106 cells


10 days




>109 cells


12 weeks
















Entry points to human fly and fly human comparisons:


1.     Do you know the name of the gene in humans?

a.     Homologene at NCBI

b.     Homophila


2.     Do you know the name of the disease?

a.     OMIM

b.     Homophila


3.     Do you know the name of the Drosophila gene?

a.     Flybase

b.     Homophila


What is Homophila and how do I use it?




The Homophila database was designed to help researches in human genetics investigate the fly homologues to human disease genes and to help investigators in fly genetics focus their research on particular genes that are relevant to human genetic disease.  Out of ~5000 human genes known to cause genetic disease 75% have homologues in flies @ an e-value of 10-10 or less.  These genes fall into most classes of human disease including neurological disorders, cancer, blood disorders, soft tissue disorders and, of course, developmental disorders.  For more details see:


L. Reiter, L. Potocki, M. Gribskov and E. Bier. 2001. A systematic analysis of human disease associated gene sequences in Drosophila melangaster. Genome Research 11:1114-1125.


Searching Homophila:


      Search by text keyword (human or fly text)

      Search by gene name (human or fly)

      Search by unique OMIM ID number

      Download complete precompiled list of homologues for a particular e-value cut off (1e-10 to 1e-300)


What makes a good candidate gene for study in the Drosophila system?


      Human disease gene function is poorly understood

      Fly counterpart highly related at the protein level to human gene (BLAST comparisons)

      Facility of genetic analysis in fly (why use a genetic model?)


o   Mutant alleles exist

o   P-elements in or nearby gene (P-screen database)

o   Mis-expression phenotype (GAL4/UAS)

      Identified loci subject to test in humans or mice – Closing the Loop!


Drosophila specific resources available online:


      Mutant alleles and UAS over-expression lines


Bloomington Stock Center    


      UAS-RNAi lines

Vienna Stock Center

NIG Stock Center, Japan


      Deficiency lines and stocks to make new deletions in the region



      RNAi primers for knock down in S2 cells

RNAi amplicon primer sets


      Finding mutations on chromosomes


Fly SNPs


Questions for Homophila Module:


1.     Identify a fly homologue to the human UBE3A gene, which causes Angelman syndrome. What reagents are available to study this gene in flies?


2.     How many human ataxias are caused by mutations in genes that have fly homologues?


3.     I work on embryo development in flies.  Are there any human diseases associated with mutations in Hedgehog?


4.     What kinds of experiments could I do in flies to understand dopa-responsive dystonia?


5.     What reagents are available to study the fly Pebble gene in vivo and in vitro?


For more information and for links to all the resources listed in this module see the Drosophila Transgenic Core website: