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)
Abstract: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, a… Show more
“…This is also reflected in the findings of others who have found complete conservation of gene order (Trower et al 1996;Miles et al 1998;Brunner et al 1999), conservation of synteny but not necessarily gene order (Kehrer-Sawatzki et al 1999;Gellner et al 1999), and extensive differences in gene order within regions of conserved synteny (Gilley et al 1999).…”
We have generated and analyzed >50,000 shotgun clones from 1059 Fugu cosmid clones. All sequences have been minimally edited and searched against protein and DNA databases. These data are all displayed on a searchable, publicly available web site at http://fugu.hgmp.mrc.ac.uk/. With an average of 50 reads per cosmid, this is virtually nonredundant sequence skimming, covering 30%-50% of each clone. This essentially random data set covers nearly 25 Mb (>6%) of the Fugu genome and forms the basis of a series of whole genome analyses which address questions regarding gene density and distribution in the Fugu genome and the similarity between Fugu and mammalian genes. The Fugu genome, with eight times less DNA but a similar gene repertoire, is ideally suited to this type of study because most cosmids contain more than one identifiable gene. General features of the genome are also discussed. We have made some estimation of the syntenic relationship between mammals and Fugu and looked at the efficacy of ORF prediction from short, unedited Fugu genomic sequences. Comparative DNA sequence analyses are an essential tool in the functional interpretation of complex vertebrate genomes. This project highlights the utility of using the Fugu genome in this kind of study.Despite massive investment in genome mapping and DNA sequencing over the last 10 years, large-scale sequencing of vertebrate genomes has been initiated only very recently. This is partly because the initial emphasis has been on developing mapping, sequencing, and assembly technologies and partly because sequence-ready contigs of large regions of the human genome have not been available. Many valuable lessons have been learned-at no small expense-from the bacterial, yeast, and, in particular, the Caenorhabditis elegans projects. It is also clear, however, that mammalian genomes may present additional problems relating to the generation of cloned DNA from some regions, sequence assembly of highly repetitive DNA, and the large size of the genomes involved.To interpret much of the data, comparative sequencing of genomic regions from other vertebrates will be necessary. The identification of conserved sequences across species has always been a key technique in the identification of genes. In addition, sequence comparison in invertebrate projects has identified many genes by sequence similarity and in many cases has allowed speculation on function. Now that the resolution of genomes is approaching the single base pair, powerful analytical methods need to be used to define the many elements-both coding and noncoding-that are contained within the human genome.Despite the need for comparison, there is little investment in other vertebrate sequencing projects at this time. Small regions of conserved synteny within the mouse genome have been pinpointed for complete genomic sequencing, and this will provide an opportunity to compare not only precise orders of genes but also regions in and around the coding sequence itself. This should lead to the identification of other con...
“…This is also reflected in the findings of others who have found complete conservation of gene order (Trower et al 1996;Miles et al 1998;Brunner et al 1999), conservation of synteny but not necessarily gene order (Kehrer-Sawatzki et al 1999;Gellner et al 1999), and extensive differences in gene order within regions of conserved synteny (Gilley et al 1999).…”
We have generated and analyzed >50,000 shotgun clones from 1059 Fugu cosmid clones. All sequences have been minimally edited and searched against protein and DNA databases. These data are all displayed on a searchable, publicly available web site at http://fugu.hgmp.mrc.ac.uk/. With an average of 50 reads per cosmid, this is virtually nonredundant sequence skimming, covering 30%-50% of each clone. This essentially random data set covers nearly 25 Mb (>6%) of the Fugu genome and forms the basis of a series of whole genome analyses which address questions regarding gene density and distribution in the Fugu genome and the similarity between Fugu and mammalian genes. The Fugu genome, with eight times less DNA but a similar gene repertoire, is ideally suited to this type of study because most cosmids contain more than one identifiable gene. General features of the genome are also discussed. We have made some estimation of the syntenic relationship between mammals and Fugu and looked at the efficacy of ORF prediction from short, unedited Fugu genomic sequences. Comparative DNA sequence analyses are an essential tool in the functional interpretation of complex vertebrate genomes. This project highlights the utility of using the Fugu genome in this kind of study.Despite massive investment in genome mapping and DNA sequencing over the last 10 years, large-scale sequencing of vertebrate genomes has been initiated only very recently. This is partly because the initial emphasis has been on developing mapping, sequencing, and assembly technologies and partly because sequence-ready contigs of large regions of the human genome have not been available. Many valuable lessons have been learned-at no small expense-from the bacterial, yeast, and, in particular, the Caenorhabditis elegans projects. It is also clear, however, that mammalian genomes may present additional problems relating to the generation of cloned DNA from some regions, sequence assembly of highly repetitive DNA, and the large size of the genomes involved.To interpret much of the data, comparative sequencing of genomic regions from other vertebrates will be necessary. The identification of conserved sequences across species has always been a key technique in the identification of genes. In addition, sequence comparison in invertebrate projects has identified many genes by sequence similarity and in many cases has allowed speculation on function. Now that the resolution of genomes is approaching the single base pair, powerful analytical methods need to be used to define the many elements-both coding and noncoding-that are contained within the human genome.Despite the need for comparison, there is little investment in other vertebrate sequencing projects at this time. Small regions of conserved synteny within the mouse genome have been pinpointed for complete genomic sequencing, and this will provide an opportunity to compare not only precise orders of genes but also regions in and around the coding sequence itself. This should lead to the identification of other con...
“…The order of these genes is conserved in Fugu and all three are located within a 12.4-kb region (Trower et al 1996). These data show that the synteny has been conserved between Fugu and GENOME RESEARCH @ 1189 …”
Section: Conserved Linkage Between Fugu Pdgfr and Csf1rmentioning
We have cloned and sequenced the teleost homoiogs of the human genes encoding platelet-derived growth factor receptor-13 (PDGFRI3) and macrophage colony-stimulating factor I receptor (CSF1R) from the puffer fish Fugu rubripes. The Fugu PDGFRI3 and CSFIR genes each consist of 21 coding exons similar to the human CSFIR gene, but are considerably smaller than their human counterparts because of the smaller introns. Furthermore, the two Fugu genes are linked tandemly in a head-to-tail array similar to their human homologs with 2.2 kb of intergenic sequence. Amino acid sequences of the Fugu and human PDGFRI3 and CSFIR genes show an overall homology of 45% and 39%, respectively, with the kinase domains showing a much higher degree of conservation. Dot-matrix analysis revealed several short stretches of conserved sequences in the 3' untranslated regions of the PDGFRI3 genes and the adjacent promoter regions of the CSFIR genes. These conserved sequences may have a role in the regulation of expression of either or both of these closely linked genes.[The sequence data described in this paper have been submitted to GenBank under accession no. U63926.]The Japanese puffer fish Fugu rubripes has a small genome of 390 Mb which is -8 times smaller than the mammalian genomes (Brenner et al. 1993). Because teleosts have a body plan similar to that of mammals and possess most of their complex physiological functions, it is not surprising that the Fugu genome has a gene repertoire comparable to that of mammals (Brenner et al. 1993).This implies that the gene density in the Fugu genome is higher than in mammalian genomes.The compact genome of Fugu with small introns and a low abundance of repetitive elements (Brenner et
“…Recently, an ATF3 homolog has also been isolated in the Japanese puer®sh Fugu rubripes (Trower et al, 1996;Venkatesh et al, 2000). In rodents, ATF3 is expressed at relatively low level in most cell types (Freeman et al, 1998) with the exception of skeletal muscle, intestine, and stomach tissues .…”
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.