Comparative sequence analysis of the human and pufferfish Huntington's disease genes

Baxendale, Sarah; Abdulla, Sarah; Elgar, Greg; Buck, David; Berks, Mary; Micklem, Gos; Durbin, Richard; Bates, Gillian P.; Brenner, Sydney; Beck, Stephan; Lehrach, Hans

doi:10.1038/ng0595-67

Cited by 131 publications

(55 citation statements)

References 51 publications

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“…Intragenic DNA is also reduced in pufferfish genes (24,25), including the Fugu homologue of the Huntington disease gene (26). This was also observed in the genes isolated from the 4D7 cosmid.…”

mentioning

confidence: 65%

Conservation of synteny between the genome of the pufferfish (Fugu rubripes) and the region on human chromosome 14 (14q24.3) associated with familial Alzheimer disease (AD3 locus)

Trower¹,

Orton²,

Purvis³

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

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The genome of the pufferfish (Fugu rubripes) (400 Mb) is -7.5 times smaller than the human genome, but it has a similar gene repertoire to that of man. If regions of the two genomes exhibited conservation of gene order (i.e., were syntenic), it should be possible to reduce dramatically the effort required for identification of candidate genes in human disease loci by sequencing syntenic regions of the compact Fugu genome. We have demonstrated that three genes (dihydrolipoamide succinyltransferase, S31iii125, and S20il5), which are linked to FOS in the familial Alzheimer disease locus (AD3) on human chromosome 14, have homologues in the Fugu genome adjacent to Fugu cFOS. The relative gene order of cFOS, S31iii125, and S20i15 was the same in both genomes, but in Fugu these three genes lay within a 12.4-kb region, compared to >600 kb in the human AD3 locus. These results demonstrate the conservation of synteny between the genomes of Fugu and man and highlight the utility of this approach for sequence-based identification of genes in human disease loci.

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mentioning

confidence: 65%

Conservation of synteny between the genome of the pufferfish (Fugu rubripes) and the region on human chromosome 14 (14q24.3) associated with familial Alzheimer disease (AD3 locus)

Trower¹,

Orton²,

Purvis³

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

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“…The sequence homology search was performed first by pairwise comparisons using the GCG programs BESTFIT and BETTERFIT on both strands. ICATOOLS and PRINTREPEATS programs (23) were then used to search larger tracts of sequence for short similarity blocks, to analyze in more detail the conserved regions, and to generate the multiple nucleotide sequence comparison.…”

Section: Methodsmentioning

confidence: 99%

The conserved role of Krox-20 in directing Hox gene expression during vertebrate hindbrain segmentation.

Nonchev¹,

Maconochie²,

Vesque³

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

110

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Transient segmentation in the hindbrain is a fundamental morphogenetic phenomenon in the vertebrate embryo, and the restricted expression of subsets ofHox genes in the developing rhombomeric units and their derivatives is linked with regional specification. Here we show that patterning of the vertebrate hindbrain involves the direct upregulation of the chicken and pufferfish group 2 paralogous genes, Hoxb-2 and Noxa-2, in rhombomeres 3 and 5 (r3 and r5) by the zinc finger gene Krox-20. We identified evolutionarily conserved r3/r5 enhancers that contain high affinity binding sites capable of mediating transactivation by Krox-20. In addition to conservation of binding sites critical for activity in the chicken Hoxa-2 and pufferfish Hoxb-2 genes, the r3/r5 enhancers are also characterized by the presence of a number of identical motifs likely to be involved in cooperative interactions with Krox-20 during the process of hindbrain patterning in vertebrates.

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“…The greater evolutionary distance between Fugu and human can be exploited to determine functional domains, as these regions are likely to show a higher degree of sequence conservation. Hence, this approach has previously led to the discovery of important functional protein domains (Baxendale et al, 1995;Caldas et al, 1998).…”

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confidence: 99%

Comparative analysis of the ETV6 gene in vertebrate genomes from pufferfish to human

Montpetit

Sinnett

2001

Oncogene

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The ETV6 gene encodes an Ets-like transcription factor that is frequently rearranged in leukemias. While some of the functions of ETV6 have been uncovered recently, little is known about the key structural elements involved. Comparative genome analysis may provide novel insights into gene evolution and functions. In this study, we cloned and sequenced the homologue of ETV6 from the compact genome of the pu er®sh Fugu rubripes (fETV6). The genomic structure of the fETV6 gene was investigated by sequence analysis of a contig of genomic clones. The fETV6 gene, composed of eight exons, spans about 15 kb and is 16 times smaller than its human counterpart mainly because of the reduced intron size. Three of the seven introns of fETV are unusually large (more than 2 kb), including the 8.2 kb intron 2. The gene codes for a protein of 465 amino acids that is highly related to its human homologue, exhibiting an overall identity of 58% (72% similarity). To investigate the functional and evolutionary aspects of ETV6, we undertook a comparative analysis of this gene from various vertebrates (human, mouse, chicken, zebra®sh and Fugu). As expected, the PNT and ETS domains were highly conserved, with on average 81 and 95% peptide sequence identity, respectively. In addition, we found several new highly conserved regions within the central section of the protein that are likely to represent further functional or structural domains, which may be associated with the transcription repression capacity of this protein. We also found conserved putative regulatory elements in the promoter as well as in the large intron 2 of fETV6. The information derived from this comparative analysis will serve as the basis for more precise functional studies of ETV6 gene regulation and function. Oncogene (2001) 20, 3437 ± 3442.

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Comparative sequence analysis of the human and pufferfish Huntington's disease genes

Cited by 131 publications

References 51 publications

Conservation of synteny between the genome of the pufferfish (Fugu rubripes) and the region on human chromosome 14 (14q24.3) associated with familial Alzheimer disease (AD3 locus)

Conservation of synteny between the genome of the pufferfish (Fugu rubripes) and the region on human chromosome 14 (14q24.3) associated with familial Alzheimer disease (AD3 locus)

The conserved role of Krox-20 in directing Hox gene expression during vertebrate hindbrain segmentation.

Comparative analysis of the ETV6 gene in vertebrate genomes from pufferfish to human

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