Related Experiment Videos
Evolutionary constraints on the Disrupted in Schizophrenia locus.
Martin S Taylor1, Rebecca S Devon, J Kirsty Millar
1Medical Genetics Section, Molecular Medicine Centre, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK. martin.taylor@well.ox.ac.uk
Genomics
|February 8, 2003
Summary
The Disrupted in Schizophrenia (DISC) locus shows conserved gene order across species, but complex transcription is not conserved. DISC1 protein features remain conserved despite rapid sequence divergence.
Area of Science:
- Genomics
- Neuroscience
- Comparative Biology
Background:
- The Disrupted in Schizophrenia (DISC) locus on chromosome 1q42 is linked to major mental illnesses.
- Human DISC locus exhibits complex transcription, including alternate splicing and antisense transcripts.
Purpose of the Study:
- To compare the genomic sequence and transcription maps of the DISC locus across species.
- To identify conserved and divergent features of the DISC locus.
Main Methods:
- Comparative genomic sequence analysis.
- Transcription map comparison between human, mouse, pufferfish, and zebrafish.
- Analysis of gene order, orientation, and transcript conservation.
Main Results:
- Gene order and orientation of EGLN1, TSNAX, and DISC1 are conserved between mammals and Fugu rubripes.
- Intergenic splicing and short intergenic transcripts are not conserved.
- Alternate splice forms of DISC1 are conserved, but genomic structure is not.
- DISC1 amino acid sequence diverges rapidly, with conserved nuclear localization signals and coiled-coil blocks.
Conclusions:
- While the DISC locus's gene order is evolutionarily conserved, its complex transcriptional features are not.
- Specific functional domains within the DISC1 protein are conserved, suggesting functional importance despite rapid sequence evolution.