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Mike Fried - One of the best experts on this subject based on the ideXlab platform.
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isolation and genomic analysis of the human surf 6 gene a member of the Surfeit locus
Gene, 2000Co-Authors: Charalambos Magoulas, Mike FriedAbstract:Abstract The human Surfeit locus contains at least six tightly clustered genes (Surf-1 to Surf-6) of which five (Surf-1 to Surf-5) have been characterised and found not to share any sequence homology. The organisation and juxtaposition of the Surfeit genes are conserved between human and mouse. The Surf-6 gene that encodes a novel nucleolar-matrix protein with nucleic-acid binding properties has been characterised in mouse. In this work, we have isolated and analysed the human Surf-6 homologue and determined its genomic organisation in the Surfeit locus. The human Surf-6 gene has five exons spread over a distance of 4.3 kb and has features of a housekeeping gene being ubiquitously expressed, having its 5′ end located within a CpG rich island and lacking a canonical TATA box. The intragenic region between the 3′ end of the Surf-5 gene and the 5′ end of the Surf-6 gene is 3.2 kb and contains a pseudogene of the ribosomal protein gene rpL21. The putative human Surf-6 protein is 361 amino acids long and includes motifs found in both the mouse and fish Surf-6 homologues, which may underlie the functions of Surf-6. Three amino acid polymorphisms have been detected at codons 163, 175 and 311 by SSCP analysis.
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the human Surfeit locus
Genomics, 1998Co-Authors: Trevor Duhig, Christiana Ruhrberg, Mike FriedAbstract:The organization of the human Surfeit locus containing the six sequence-unrelated housekeeping genes Surf-1 to Surf-6 (HGMW-approved symbols SURF1-SURF6) has been determined. The human Surfeit locus occupies about 60 kb of DNA, and the tightly clustered gene organization and the juxtaposition of the human genes are similar to the mouse and chicken Surfeit loci with the 5' end of each gene associated with a CpG-rich island. Whereas in the mouse the Surf-2 and Surf-4 genes overlap at their 3' ends, the human Surf-2 and Surf-4 genes have been found to be separated by 302 bp due to a much shorter 3' untranslated region in the human Surf-2 gene. The distance between the 3' ends of the human Surf-1 and Surf-3 genes is 374 bp, and the distance between the 5' ends of the human Surf-3 and Surf-5 genes is only 112 bp. Unusually the human Surf-5 gene contains an intron in its 5' untranslated region not found in the mouse or rat Surf-5 genes. This additional intron is also found in the Surf-5 gene of both Old and New World monkeys, being generated before the divergence of human and prosimians but after the divergence of primates and rodents. A contig of 200 kb containing the human Surfeit locus has been constructed from overlapping cosmid, P1, and PAC clones. Approximately 40 kb proximal to the 3' end of the Surf-6 gene, the 5' region of the ABO glycosyltransferase gene has been detected. This allows us to determine the orientation of the Surfeit and ABO loci with respect to each other and to the telomere and centromere of human chromosome 9.
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the comparative genomic structure and sequence of the Surfeit gene homologs in the puffer fish fugu rubripes and their association with cpg rich islands
Genome Research, 1997Co-Authors: Niall Armes, Jonathan Gilley, Mike FriedAbstract:: The puffer fish Fugu rubripes (Fugu) has a compact genome approximately one-seventh the size of man, mainly owing to small intron size and the presence of few dispersed repetitive DNA elements, which greatly facilitates the study of its genes at the genomic level. It has been shown previously that, whereas the Surfeit genes are tightly clustered at a single locus in mammals and birds, the genes are found at three separate loci in the Fugu genome. Here, Fugu gene homologs of all six Surfeit genes (Surf-1 to Surf-6) have been cloned and sequenced, and their gene structure has been compared with that of their mammalian and avian homologs. The predicted protein products of each gene are well conserved between vertebrate species, and in most cases their gene structures are identical to their mammalian and avian homologs except for the Fugu Surf-6 gene, which was found to lack an intron present in the mouse gene. In addition, we have identified conserved regulatory elements at the 5' and 3' ends of the Surf-3/rpL7a gene by comparison with the mammalian and chicken Surf-3/rpL7a gene homologs, including the presence of a polypyrimidine tract at the extreme 5' end of this ribosomal protein gene. The Fugu Surfeit gene homologs appear to be associated with CpG-rich islands, like the Surfeit genes in higher vertebrates, but these Fugu CpG islands are similar to the nonclassical islands characteristic of other fish species. Our observations support the use of the Fugu genome to study vertebrate gene structure, to predict the structure of mammalian genes, and to identify vertebrate regulatory elements. [The sequence data described in this paper have been submitted to the data library under accession nos. Y15170 (Surf-2, Surf-4), Y15171 (Surf-3, Surf-1, Surf-6), and Y15172 (Surf-5.)]
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A high frequency polymorphism in the candidate region for Tuberous Sclerosis 1 (TSC1) at 9q34
Annals of Human Genetics, 1996Co-Authors: T. Duhig, Mike FriedAbstract:The Surfeit locus contains at least six tightly clustered housekeeping genes (Surf-1 to -6) with novel features (Huxley & Fried, 1990). In contrast to the tens to hundreds of kilobases found between most adjacent mammalian genes only a small region separates any two adjacent Surfeit genes. The organization of the Surfeit locus and the juxtaposition of the Surfeit genes is conserved between mouse, human and chicken (600 million years of divergent evolution) (Williams et al. 1988; Yon et al. 1993; Colombo et al. 1992) indicating that the Surfeit locus gene organization may have biological significance. The Surfeit locus has been mapped to human chromosome band 9q34, within the candidate region for Tuberous Sclerosis 1 (TSC1) (Yon et al. 1993). In the process of screening for mutations correlated with TSC1 by single strand conformation polymorphism (SSCP) (Orita et al. 1989) in this genomic region we detected a polymorphism which occurs at a high frequency.
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surf5 a gene in the tightly clustered mouse Surfeit locus is highly conserved and transcribed divergently from the rpl7a surf3 gene
Genomics, 1995Co-Authors: Ken Garson, Trevor Duhig, Niall Armes, Paolo Colombo, Mike FriedAbstract:The four previously characterized genes (Surf1 to 4) of the mouse Surfeit locus do not share any sequence homology, and the transcription of each gene alternates with respect to its neighbors. Adjacent Surfeit genes are separated by very small distances, and two of the genes overlap at their 3{prime} ends. In this work we have further defined the Surfeit gene cluster by the isolation of Surf5, a fifth gene of the locus, and determination of its relationship to the other Surfeit genes. Surf5 does not share any sequence homology with the four cloned Surfeit genes. The transcription of Surf5 is divergent with respect to its neighbor the Surf3 gene, and the 5{prime} ends of Surf5 and Surf3 are separated by only 159 bp, suggesting the presence of a second bidirectional promoter in the locus. The 3{prime} end of Surf5 maps only 68 bp away from the processed 3{prime} end of a pseudogene. The human and partial chicken Surf5 coding regions show greater than 95% identity, and a Caenorhabditis elegans homologue shows 38% identity and 56% similarity with the mouse Surf5 amino acid sequence. The 3.5-kb transcript of Surf5 encodes a small hydrophilic protein of 140 amino acid residues, which differsmore » from the ribosomal protein L7a encoded by the Surf3 gene or the integral membrane protein encoded by the Surf4 gene. Subcellular fractionation located the Surf5 protein to the soluble fraction of the cytoplasm. The Surfeit locus appears to represent a novel type of gene cluster in which the genes are unrelated by sequence or function; however, their organization may play a role in their gene expression. 44 refs., 5 figs.« less
M Fried - One of the best experts on this subject based on the ideXlab platform.
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Surfeit locus gene homologs are widely distributed in invertebrate genomes
Molecular and Cellular Biology, 1996Co-Authors: N Armes, M FriedAbstract:The mouse Surfeit locus contains six sequence-unrelated genes (Surf-1 to -6) arranged in the tightest gene cluster so far described for mammals. The organization and juxtaposition of five of the Surfeit genes (Surf-1 to -5) are conserved between mammals and birds, and this may reflect a functional or regulatory requirement for the gene clustering. We have undertaken an evolutionary study to determine whether the Surfeit genes are conserved and clustered in invertebrate genomes. Drosophila melanogaster and Caenorhabditis elegans homologs of the mouse Surf-4 gene, which encodes an integral membrane protein associated with the endoplasmic reticulum, have been isolated. The amino acid sequences of the Drosophila and C. elegans homologs are highly conserved in comparison with the mouse Surf-4 protein. In particular, a dilysine motif implicated in endoplasmic reticulum localization of the mouse protein is conserved in the invertebrate homologs. We show that the Drosophila Surf-4 gene, which is transcribed from a TATA-less promoter, is not closely associated with other Drosophila Surfeit gene homologs but rather is located upstream from sequences encoding a homolog of a yeast seryl-tRNA synthetase protein. There are at least two closely linked Surf-3/rpL7a genes or highly polymorphic alleles of a single Surf-3/rpL7a gene in the C. elegans genome. The chromosomal locations of the C. elegans Surf-1, Surf-3/rpL7a, and Surf-4 genes have been determined. In D. melanogaster the Surf-3/rpL7a, Surf-4, and Surf-5 gene homologs and in C. elegans the Surf-1, Surf-3/rpL7a, Surf-4, and Surf-5 gene homologs are located on completely different chromosomes, suggesting that any requirement for the tight clustering of the genes in the Surfeit locus is restricted to vertebrate lineages.
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the genomic organization of the region containing the drosophila melanogaster rpl7a surf 3 gene differs from those of the mammalian and avian Surfeit loci
Molecular and Cellular Biology, 1995Co-Authors: N Armes, M FriedAbstract:The Surf-3 gene of the unusually tight mouse Surfeit locus gene cluster has been identified as the highly conserved ribosomal protein gene L7a (rpL7a). The topography and juxtaposition of the Surfeit locus genes are conserved for the 600 million years of divergent evolution between mammals and birds. This suggests cis interaction and/or coregulation of the genes and suggests that, within this locus, gene organization plays an important role in gene expression. The further evolutionary conservation of the organization of the Surfeit locus was investigated. A cDNA encoding the Drosophila melanogaster homolog of the Surf-3/rpL7a gene was cloned, was shown to be present as a single copy, and was expressed constitutively at high levels throughout development. Genomic cosmid clones encompassing the gene and its surrounding DNA were isolated. The gene was determined to have five introns, of which two were located in the 5' untranslated region of the gene. The remaining three introns had splice sites at positions equivalent to those found in the Surf-3/rpL7a mammalian homologs. S1 analysis and 5' rapid amplification of cDNA ends both confirmed the start of transcription to occur in a polypyrimidine tract in the absence of a TATA box in the promoter. The genomic region around the Surf-3/rpL7a gene was analyzed by low-stringency hybridization with murine Surfeit gene probes, by partial sequence analysis, and by hybridization of fragments to Northern (RNA) blots. No homologs of other members of the Surfeit gene cluster were detected in close proximity to the D. melanogaster Surf-3/rpL7a gene. However, a gene which was detected directly 3' to the Surf-3/rpL7a gene was shown to encode a homolog of a mammalian serine-pyruvate aminotransferase.
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the mouse Surfeit locus contains a cluster of six genes associated with four cpg rich islands in 32 kilobases of genomic dna
Molecular and Cellular Biology, 1990Co-Authors: Clare Huxley, M FriedAbstract:The clustered arrangement (no two adjacent genes are separated by more than 73 base pairs [bp] and two genes overlap by 133 bp at their 3' ends) of the four genes (Surf-1 to -4) identified so far in the mouse Surfeit locus (T. Williams, J. Yon, C. Huxley, and M. Fried, Proc. Natl. Acad. Sci. USA 85:3527-3530, 1988) is the tightest gene clustering found in any mammalian genome to date and strongly suggests the possibility of cis-interaction and/or coregulation of gene expression. Thus, we are analyzing the Surfeit genes in detail and are defining the extent of the cluster. Here we present the sequence of the entire Surf-4 gene and define the 3' and 5' extents of its mRNAs. The Surf-4 gene has heterogeneous transcriptional start sites, and its 5' end lies in a CpG-rich island. The gene specifies three mRNAs, with the two most abundant mRNAs differing in the locations of their 3' polyadenylation sites. Only the most abundant Surf-4 mRNA would overlap the 3' end of the Surf-2 gene by 133 bp. Two new genes (Surf-5 and Surf-6) have been identified in the Surfeit gene cluster by Northern (RNA) blot analysis. The 5' end of Surf-6 lies within the CpG-rich island about 8 kilobases (kb) from the CpG-rich island containing the 5' end of Surf-3, and Surf-5 lies between Surf-3 and Surf-6. Thus, the cluster contains a unique arrangement of four CpG-rich islands within 32 kb associated with the 5' ends of the six Surfeit genes. The neighboring CpG-rich islands have been located 500 and 100 kb distant on either side of the Surfeit cluster, indicating that the end of the cluster of islands has been reached.
Charalambos Magoulas - One of the best experts on this subject based on the ideXlab platform.
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isolation and genomic analysis of the human surf 6 gene a member of the Surfeit locus
Gene, 2000Co-Authors: Charalambos Magoulas, Mike FriedAbstract:Abstract The human Surfeit locus contains at least six tightly clustered genes (Surf-1 to Surf-6) of which five (Surf-1 to Surf-5) have been characterised and found not to share any sequence homology. The organisation and juxtaposition of the Surfeit genes are conserved between human and mouse. The Surf-6 gene that encodes a novel nucleolar-matrix protein with nucleic-acid binding properties has been characterised in mouse. In this work, we have isolated and analysed the human Surf-6 homologue and determined its genomic organisation in the Surfeit locus. The human Surf-6 gene has five exons spread over a distance of 4.3 kb and has features of a housekeeping gene being ubiquitously expressed, having its 5′ end located within a CpG rich island and lacking a canonical TATA box. The intragenic region between the 3′ end of the Surf-5 gene and the 5′ end of the Surf-6 gene is 3.2 kb and contains a pseudogene of the ribosomal protein gene rpL21. The putative human Surf-6 protein is 361 amino acids long and includes motifs found in both the mouse and fish Surf-6 homologues, which may underlie the functions of Surf-6. Three amino acid polymorphisms have been detected at codons 163, 175 and 311 by SSCP analysis.
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the surf 6 gene of the mouse Surfeit locus encodes a novel nucleolar protein
DNA and Cell Biology, 1996Co-Authors: Charalambos Magoulas, Michael FriedAbstract:ABSTRACT The Surfeit locus contains the tightest cluster of mammalian genes so far described. The five Surfeit genes (Surf-1 to -5) that have been previously isolated and characterized do not share...
Michael Fried - One of the best experts on this subject based on the ideXlab platform.
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the surf 6 gene of the mouse Surfeit locus encodes a novel nucleolar protein
DNA and Cell Biology, 1996Co-Authors: Charalambos Magoulas, Michael FriedAbstract:ABSTRACT The Surfeit locus contains the tightest cluster of mammalian genes so far described. The five Surfeit genes (Surf-1 to -5) that have been previously isolated and characterized do not share...
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The Surf-1 and Surf-2 genes and their essential bidirectional promoter elements are conserved between mouse and human.
DNA and Cell Biology, 1994Co-Authors: Andrew Lennard, Kevin Gaston, Michael FriedAbstract:ABSTRACT The organization of the Surfeit locus and the juxtaposition of at least five of the Surfeit genes (Surf−1 to −5) are conserved between mouse and human (Williams et al., 1988; Yon et al., 1...
N Armes - One of the best experts on this subject based on the ideXlab platform.
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Surfeit locus gene homologs are widely distributed in invertebrate genomes
Molecular and Cellular Biology, 1996Co-Authors: N Armes, M FriedAbstract:The mouse Surfeit locus contains six sequence-unrelated genes (Surf-1 to -6) arranged in the tightest gene cluster so far described for mammals. The organization and juxtaposition of five of the Surfeit genes (Surf-1 to -5) are conserved between mammals and birds, and this may reflect a functional or regulatory requirement for the gene clustering. We have undertaken an evolutionary study to determine whether the Surfeit genes are conserved and clustered in invertebrate genomes. Drosophila melanogaster and Caenorhabditis elegans homologs of the mouse Surf-4 gene, which encodes an integral membrane protein associated with the endoplasmic reticulum, have been isolated. The amino acid sequences of the Drosophila and C. elegans homologs are highly conserved in comparison with the mouse Surf-4 protein. In particular, a dilysine motif implicated in endoplasmic reticulum localization of the mouse protein is conserved in the invertebrate homologs. We show that the Drosophila Surf-4 gene, which is transcribed from a TATA-less promoter, is not closely associated with other Drosophila Surfeit gene homologs but rather is located upstream from sequences encoding a homolog of a yeast seryl-tRNA synthetase protein. There are at least two closely linked Surf-3/rpL7a genes or highly polymorphic alleles of a single Surf-3/rpL7a gene in the C. elegans genome. The chromosomal locations of the C. elegans Surf-1, Surf-3/rpL7a, and Surf-4 genes have been determined. In D. melanogaster the Surf-3/rpL7a, Surf-4, and Surf-5 gene homologs and in C. elegans the Surf-1, Surf-3/rpL7a, Surf-4, and Surf-5 gene homologs are located on completely different chromosomes, suggesting that any requirement for the tight clustering of the genes in the Surfeit locus is restricted to vertebrate lineages.
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the genomic organization of the region containing the drosophila melanogaster rpl7a surf 3 gene differs from those of the mammalian and avian Surfeit loci
Molecular and Cellular Biology, 1995Co-Authors: N Armes, M FriedAbstract:The Surf-3 gene of the unusually tight mouse Surfeit locus gene cluster has been identified as the highly conserved ribosomal protein gene L7a (rpL7a). The topography and juxtaposition of the Surfeit locus genes are conserved for the 600 million years of divergent evolution between mammals and birds. This suggests cis interaction and/or coregulation of the genes and suggests that, within this locus, gene organization plays an important role in gene expression. The further evolutionary conservation of the organization of the Surfeit locus was investigated. A cDNA encoding the Drosophila melanogaster homolog of the Surf-3/rpL7a gene was cloned, was shown to be present as a single copy, and was expressed constitutively at high levels throughout development. Genomic cosmid clones encompassing the gene and its surrounding DNA were isolated. The gene was determined to have five introns, of which two were located in the 5' untranslated region of the gene. The remaining three introns had splice sites at positions equivalent to those found in the Surf-3/rpL7a mammalian homologs. S1 analysis and 5' rapid amplification of cDNA ends both confirmed the start of transcription to occur in a polypyrimidine tract in the absence of a TATA box in the promoter. The genomic region around the Surf-3/rpL7a gene was analyzed by low-stringency hybridization with murine Surfeit gene probes, by partial sequence analysis, and by hybridization of fragments to Northern (RNA) blots. No homologs of other members of the Surfeit gene cluster were detected in close proximity to the D. melanogaster Surf-3/rpL7a gene. However, a gene which was detected directly 3' to the Surf-3/rpL7a gene was shown to encode a homolog of a mammalian serine-pyruvate aminotransferase.
