Transcript Bioinformatics_workshop

Genomics: genes to conserved function to disease.
Intended Use: General Genetics (Griffiths, et al., text)
~ 50 students, mostly sophomores, a few freshmen
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 .
The Model System is Drosophila
The Drosophila eyeless gene
pax 6 in humans
small eye in mouse
flybase.bio.indiana.edu/
Conserved domains in eyeless/PAX6 using PROSITE
(857 aa)
Paired domain
Homeodomain
PAX 6 DNA binding protein, transcription factor
Ectopic expression of eyeless
PAX 6 gene: paired homeobox
Pdf PNAS 94:2421-2426
Pax 6 mastering eye morphogenesis and eye evolution
TIG September 1999, volume 15, No. 9
TIG September
1999, volume 15, No.
9
Genomic structure, evolutionary conservation and aniridia
mutations in the human PAX6 gene.
Related Articles, Links
Glaser T, Walton DS, Maas RL.
Department of Medicine, Brigham and Women's Hospital, Harvard
Medical School, Boston, Massachusetts 02115.
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. 1992 Nov;2(3):232-9.