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 DNA, 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.
We sequenced the human MB1 gene from a cosmid clone mapping to chromosome 14q11.2-12. The gene spans about 6 kilobases and contains three exons and two introns. There was no evidence of an alternative leader exon, which is a characteristic of the major histocompatibility complex (MHC)-encoded LMP7 gene, the closest relative of MB1, with which it shares 67% amino acid identity. Conceptual translation of the 5' end of the gene calls for a cleaved leader sequence of 59 amino acids, consistent with western blot data. None of the MB1 gene's three exons were coincident with any of the six exons in LMP7. In contrast, in the delta-encoding gene and its counterpart, the MHC-encoded LMP2 gene (59% amino acid identity), all six exons are arranged at equivalent positions in respect to the coding frame. The unique structure of MB1 implies a separate origin or different selection pressures acting at this particular locus. DNA repeat analysis provides information on the minimum time of separation of the MB1/LMP7 pair of genes.
We sequenced the human MB1 gene from a cosmid clone mapping to chromosome 14q11.2-12. The gene spans about 6 kilobases and contains three exons and two introns. There was no evidence of an alternative leader exon, which is a characteristic of the major histocompatibility complex (MHC)-encoded LMP7 gene, the closest relative of MB1, with which it shares 67% amino acid identity. Conceptual translation of the 5' end of the gene calls for a cleaved leader sequence of 59 amino acids, consistent with western blot data. None of the MB1 gene's three exons were coincident with any of the six exons in LMP7. In contrast, in the delta-encoding gene and its counterpart, the MHC-encoded LMP2 gene (59% amino acid identity), all six exons are arranged at equivalent positions in respect to the coding frame. The unique structure of MB1 implies a separate origin or different selection pressures acting at this particular locus. DNA repeat analysis provides information on the minimum time of separation of the MB1/LMP7 pair of genes.
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