Evolutionary constraints on the Disrupted in Schizophrenia locus.
The Disrupted in Schizophrenia (DISC) locus on human chromosome 1q42 has been strongly implicated by genetic studies as a susceptibility locus for major mental illnesses. In humans the locus is transcriptionally complex, with multiple alternate splicing events, antisense transcription, and intergenic splicing all evident. We have compared the genomic sequence and transcription maps of this locus between human, mouse, pufferfish (Fugu rubripes), and, in part, zebrafish (Danio rerio). The order and orientation of EGLN1, TSNAX, and DISC1 genes are conserved between mammals and F. rubripes. Intergenic splicing and short intergenic transcripts are not found to be conserved features. DISC2, a putative noncoding transcript partially antisense to DISC1, is not conserved in mouse or F. rubripes. Alternate splice forms of the protein-coding DISC1 gene are conserved even though the genomic structure is not. The amino acid sequence of DISC1 is diverging rapidly, although a putative nuclear localization signal and discrete blocks of coiled coil are specifically conserved features.
Taylor
Martin S
MS
Medical Genetics Section, Molecular Medicine Centre, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK. martin.taylor@well.ox.ac.uk
Devon
Rebecca S
RS
Millar
J Kirsty
JK
Porteous
David J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D001523:Mental Disorders / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012326:RNA Splicing; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D016415:Sequence Alignment; D023741:Takifugu / Q000235:genetics
C448722:DISC2 gene product, human; C498794:Disc1 protein, mouse; D009419:Nerve Tissue Proteins; D062085:RNA, Long Noncoding; D012333:RNA, Messenger