Nature Genetics
10, 67 - 76 (1995)
doi:10.1038/ng0595-67
Comparative sequence analysis of the human and pufferfish Huntington's disease genesSarah Baxendale1, Sarah Abdulla2, Greg Elgar3, David Buck4, Mary Berks4, Gos Micklem4, Richard Durbin4, Gill Bates5, Sydney Brenner3, Stephan Beck2
& Hans Lehrach1
1Genome Analysis Laboratory, ICRF, Lincoln's Inn Fields, London WC2A 3PX, UK
2DNA Sequencing Laboratory, ICRF, Lincoln's Inn Fields, London WC2A 3PX, UK
3MRC Molecular Genetics Unit and Department of Medicine, University of Cambridge Clinical School, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
4Sanger Centre, Hinxton Hall, Hinxton, Cambs CB101RQ, UK
5Division of Medical and Molecular Genetics, United Medical and Dental Schools, Guy's Tower, Guy's Hospital, London SE1 9RT, UK Correspondence should be addressed to S. Baxendale The Huntington's disease (HD) gene encodes a novel protein with as yet no known function. In order to identify the functionally important domains of this protein, we have cloned and sequenced the homologue of the HD gene in the pufferfish, Fugu rubripes. The Fugu HD gene spans only 23 kb of genomic DMA, compared to the 170 kb human gene, and yet all 67 exons are conserved. The first coding exon, the site of the disease−causing triplet repeat, is highly conserved. However, the glutamine repeat in Fugu consists of just four residues. We also show that gene order may be conserved over longer stretches of the two genomes. Our work describes a detailed example of sequence comparison between human and Fugu and illustrates the power of the pufferfish genome as a model system in the analysis of human genes.
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