Primary goal: Provide students with a way to understand the use/value of model organisms for gene discovery. Students will use web-based Bioinformatics programs to reinforce concepts such as transcription, translation, evolutionary conservation, structure and function of a protein. Implementation: Lecture on Drosophila eyeless demonstrating how genomic analysis was used to elucidate the role of a putative “master control gene” for eye development. This will provide the web-based tools for analyzing their unknown sequence (see below). Students will be given an unknown sequence (the Drosophila patched genomic sequence containing a small deletion in a functional domain.) Questions students will answer: 1. Identify gene, intron-exon structure, translation start/stop sites. 2. Identify conserved protein domains. 3. Predict a function from the conserved domains. 4. Produce a phylogenetic tree using 5 organisms. 5. Write a paragraph relating patched to a human disease. Genomics: genes to conserved function to disease. Intended Use: General Genetics (Griffiths, et al., text) ~ 50 students, mostly sophomores, a few freshmen

The Drosophila eyeless gene The Model System is Drosophila flybase.bio.indiana.edu/ pax 6 in humans small eye in mouse

ruler: (857 aa) Conserved domains in eyeless/PAX6 using PROSITE Paired domain Homeodomain

PAX 6 DNA binding protein, transcription factor

Ectopic expression of eyeless PAX 6 gene: paired homeobox

Pdf PNAS 94:

Pax 6 mastering eye morphogenesis and eye evolution TIG September 1999, volume 15, No. 9

: Nat Genet Nov;2(3): Related Articles, Related Articles, Links Genomic structure, evolutionary conservation and aniridia mutations in the human PAX6 gene. Glaser T, Walton DS, Maas RL. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts Aniridia is a semidominant disorder in which development of the iris, lens, cornea and retina is disturbed. The mouse mutation Small eye (Sey), which has been proposed as a model for aniridia, results from defects in Pax-6, a gene containing paired-box and homeobox motifs that is specifically expressed in the developing eye and brain. To test the role of PAX6 in aniridia, we isolated human cDNA clones and determined the intron-exon structure of this gene. PAX6 spans 22 kilobases and is divided into 14 exons. Analysis of DNA from 10 unrelated aniridia patients revealed intragenic mutations in three familial and one sporadic case. These findings indicate that the human aniridia and murine Small eye phenotypes arise from homologous defects in PAX6. Nat Genet Nov;2(3):232-9.