Search PubMed⌕ Search

Biomedical subjects

F Galibert

Publications and source records attributed to F Galibert.

At least 73 records · Page 4Linked to original sources
PubMed1996

Systematic sequencing of the human HLA-A/HLA-F region: establishment of a cosmid contig and identification of a new gene cluster within 37 kb of sequence.

The class I region of the human histocompatibility complex is characterized by a high density of genes and pseudogenes and a complex structural organization. To elucidate the complete structure of the HLA-A/HLA-F region with a view to defining its contents in genes and pseudogenes, we developed a strategy of systematic sequencing. This report describes the establishment of a cosmid contig spanning most of the region and the analysis of a 37-kb sequence from one of the cosmids. Four new genes, organized with the HCG-V gene in a clustered structure, have been identified. Two of these contain a zinc finger motif characteristic of DNA-binding proteins. The former, a member of the C3HC4 protein family, is highly expressed in prostate and contains a B30-2-like sequence identified in several genes mapped within the class I region. The latter, which is ubiquitously expressed, is the human equivalent of the yeast polymerase IA12.2 subunit and of the murine tctex6 gene. Of the two other genes, one remains an anonymous gene with no particular feature, while the fourth, specifically expressed in testis, is the human equivalent of the murine tctex4 gene. This cluster, located in a region corresponding to a syntenic unit between mouse and human, appears to be highly conserved.

Amino Acid Sequence↗
PubMed1996

Life with 6000 genes.

The genome of the yeast Saccharomyces cerevisiae has been completely sequenced through a worldwide collaboration. The sequence of 12,068 kilobases defines 5885 potential protein-encoding genes, approximately 140 genes specifying ribosomal RNA, 40 genes for small nuclear RNA molecules, and 275 transfer RNA genes. In addition, the complete sequence provides information about the higher order organization of yeast's 16 chromosomes and allows some insight into their evolutionary history. The genome shows a considerable amount of apparent genetic redundancy, and one of the major problems to be tackled during the next stage of the yeast genome project is to elucidate the biological functions of all of these genes.

Amino Acid Sequence↗
PubMed1996

Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X.

The complete nucleotide sequence of Saccharomyces cerevisiae chromosome X (745 442 bp) reveals a total of 379 open reading frames (ORFs), the coding region covering approximately 75% of the entire sequence. One hundred and eighteen ORFs (31%) correspond to genes previously identified in S. cerevisiae. All other ORFs represent novel putative yeast genes, whose function will have to be determined experimentally. However, 57 of the latter subset (another 15% of the total) encode proteins that show significant analogy to proteins of known function from yeast or other organisms. The remaining ORFs, exhibiting no significant similarity to any known sequence, amount to 54% of the total. General features of chromosome X are also reported, with emphasis on the nucleotide frequency distribution in the environment of the ATG and stop codons, the possible coding capacity of at least some of the small ORFs (<100 codons) and the significance of 46 non-canonical or unpaired nucleotides in the stems of some of the 24 tRNA genes recognized on this chromosome.

Amino Acid Sequence↗
PubMed1996

Chromosomal localization and expression pattern of the RNase L inhibitor gene.

2-5A-Dependent RNase (RNase L), an important component of the 2-5A pathway, is directly implicated in the molecular mechanism of interferon action. We have cloned and sequenced following immunoscreening, a full-length cDNA that encodes the RNase L inhibitor (RLI). Northern blot analysis from a variety of human tissues revealed that two transcript forms (3.8 kb and 2.4 kb) are ubiquitously expressed but differences in levels of expression suggest a tissue-specific regulation. The RLI gene was localized to locus 4q31 by in situ hybridization indicating that this gene and other enzymes of the 2-5A pathway are not organized in cluster in the human genome.

ATP-Binding Cassette Transporters↗
PubMed1996

Identification of ACT4, a novel essential actin-related gene in the yeast Saccharomyces cerevisiae.

Actin molecules are major cytoskeleton components of all eukaryotic cells. All conventional actins that have been identified so far are 374-376 amino acids in size and exhibit at least 70% amino acid sequence identity when compared with one another. In the yeast Saccharomyces cerevisiae, one conventional actin gene ACT1 and three so-called actin-related genes, ACT2, ACT3 and ACT5, have been identified. We report here the discovery of a new actin-related gene in this organism, which we have named ACT4. The deduced protein, Act4, of 449 amino acids, exhibits only 33.4%, 26.7%, 23.4% and 29.2% identity to Act1, Act2, Act3 and Act5, respectively. In contrast, it is 68.4% identical to the product of the Schizosaccharomyces pombe Act2 gene and has a similar level of identity to other Sch. pombe Act2 homologues. This places Act4 in the Arp3 family of actin-related proteins. ACT4 gene disruption and tetrad analysis demonstrate that this gene is essential for the vegetative growth of yeast cells. The act4 mutants exhibit heterogenous morphological phenotypes. We hypothesize that Act4 may have multiple roles in the cell cycle.

Actin-Related Protein 3↗
PubMed1996

Analysis of a 62 kb DNA sequence of chromosome X reveals 36 open reading frames and a gene cluster with a counterpart on chromosome XI.

We have sequenced a 61.989 bp stretch located between genes RAD7 and FIP1 of Saccharomyces cerevisiae chromosome X. This stretch contains 36 open reading frames (ORFs) of at least 100 codons. Fourteen of these correspond to sequences previously published as HIT1, CDC8, YAP17, CBF1, NAT1, RPA12, CCT5, TOR1, RFC2, PEM2, CDC11, MIR1, STE18 and GRR1. The proteins deduced from four ORFs (YJR059w, YJR065c, YJR075w, YJR078w) have significant similarity to proteins of known function from yeast or other organisms, including S. cerevisiae serine/threonine-specific protein kinase. Schizosaccharomyces pombe Act2 protein, S. cerevisiae mannosyltransferase OCH1 protein and mouse indoleamine 2,3-dioxygenase, respectively. Four of the remaining 18 ORFs have similarity to proteins with unknown function, six are weakly similar to other known sequences, while another eight exhibit no similarity to any known sequence. In addition, three tRNA genes have been recognized. Three genes clustered within 22 kb (YJR059w, YJR061w and TOR1) have counterparts arranged within 15 kb on the left arm of chromosome XI.

Amino Acid Sequence↗
PubMed1996

Human lipoprotein lipase last exon is not translated, in contrast to lower vertebrates.

We have sequenced the first fish (zebrafish, Brachydanio rerio) lipoprotein lipase (LPL) cDNA clone. Similarities were found in mammalian LPL cDNA, but the codon spanning the last two exons (which is thus split by the last intron) is AGA (Arg) as opposed to TGA in mammals. Exon 10 is thus partially translated. These results were confirmed with rainbow trout (Oncorhynchus mykiss). We also investigated whether mammal TGA coded for selenocystein (SeCys), the 21st amino acid, but found that this was not the case: TGA does not encode SeCys but is a stop codon. It thus appears that the sense codon AGA (fish) has been transformed into a stop codon TGA (human) during the course of evolution. It remains to be determined if the "loss" of the C-terminal end of mammalian LPL protein has conferred an advantage in terms of LPL activity or, on the contrary, a disadvantage (e.g., susceptibility to diabetes or atherosclerosis).

Animals↗
PubMed1995

Human T-cell-leukemia virus type I in post-transfusional spastic paraparesis: complete proviral sequence from uncultured blood cells.

Human T-cell-leukemia virus type I (HTLV-I) is the causative agent of adult T-cell leukemia/lymphoma (ATL) and tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). The different disease outcome may be attributable to subtle mutations leading to modification of viral tropism or infectivity. Initial attempts found a very high level of sequence conservation among all HTLV-I strains. However, only one complete proviral DNA sequence is reported from a TSP/HAM patient, with a provirus derived from immortalized lymphocytes, which might be expected to be a leukemogenic variant rather than a neurotropic one. We cloned and sequenced a complete HTLV-I provirus (HTLV-IBoi) derived from the uncultured lymphocytes of a sub-acute post-transfusional TSP/HAM patient with clonal integration of HTLV-I. HTLV-IBoi proviral genome is 9033 bp long, and its overall genetic organization is similar to that of the prototype HTLV-I(ATK), without major deletions or insertions. No premature termination codon was found in the 4 open reading frames of the pX region. Divergence at the nucleotide level of HTLV-IBoi from the reported full-length HTLV-I varies from 1 to 9.4%, and indicates that it corresponds to a cosmopolitan genotype. This study did not identify specific sequences associated with neurotropic strains.

Adult↗
PubMed1995

Analysis of a 42.5 kb DNA sequence of chromosome X reveals three tRNA genes and 14 new open reading frames including a gene most probably belonging to the family of ubiquitin-protein ligases.

We have sequenced a 42,500 bp stretch located on chromosome X of Saccharomyces cerevisiae between the genes MET3 and CDC8. This stretch contains 24 open reading frames (ORFs) of at least 100 amino acids. Ten of these correspond to previously published sequences, whereas of the 14 remaining ORFs, only one, GTD892, has significant similarity to proteins from yeast or other organisms. It may belong to the family of ubiquitin-protein ligases and be involved in the ubiquitin-dependent proteolytic pathway. In addition, three tRNA genes were recognized, two of which had not been hitherto localized.

Amino Acid Sequence↗
PubMed1995

Construction of a complete genomic library of Saccharomyces cerevisiae and physical mapping of chromosome XI at 3.7 kb resolution.

A consortium of European laboratories has been organized to systematically sequence the genome of Saccharomyces cerevisiae. As part of the BIOTECH program aimed at sequencing chromosomes XI and II, we have constructed a total genomic library of yeast strain FY1679 (a direct S288C derivative) into cosmid vectors pWE15 and pOU61cos. Primary clones from four independent libraries totalling 190 genome equivalents have been stored at -80 degrees C. A subset of 1939 independent clones (six genome equivalents) was hybridized using purified chromosomes XI and X as probes. A total of 147 chromosome XI-specific cosmid clones was used to construct the physical map of that chromosome. Mapping methods included a combination of classical bottom-up strategies (fingerprinting, hybridizations) and a novel top-down strategy using I-SceI chromosome fragmentation. The 147 cosmid clones form a unique contig covering the entire chromosome XI (666 kb) with the sole exceptions of the (C1-3A)n repeats of the telomeres. Colinearity of cosmid inserts with yeast DNA was directly verified. A complete EcoRI map of chromosome XI was deduced from partial overlaps of cosmids and used for the sequencing program. Comparison of this map with the genetic map shows unexpected divergences that have been solved by subsequent genetic analysis, yet underline the necessity of independent physical mapping in genome projects.

Base Sequence↗
PubMed1995

Molecular evolution of the genes encoding receptor tyrosine kinase with immunoglobulinlike domains.

Receptor tyrosine kinases (RTK) with five, three, or seven immunoglobulinlike domains in their extracellular regions are classified as subclasses III, IV, and V, respectively. Conservation of the exon/intron structure of the downstream part of the human KIT, FMS, and FLT3 genes that encode RTK of subclass III together with the particular chromosomal localization of these genes suggests that RTKIII genes have evolved from a common ancestor by cis and trans duplications. To strengthen this model of evolution and to determine if it can be extended to RTKIV and V genes, we constructed a phylogenetic tree of RTKIII, IV, and V on the basis of a multiple alignment of their catalytic tyrosine kinase domain sequences and determined the exon/intron structure of PDGFRA (subclass III), FGFR4 (subclass IV), and FLT4 (subclass V) genes in their downstream part. Phylogenetic analyses with amino acid or nucleotide sequences both resulted in one most parsimonious tree. The phylogenetic trees obtained indicate that all three subclasses are well individuated and that RTKIII and RTKV are closer to each other than RTKIV. Furthermore, RTKIII and FLT4 (subclass V) genes possess the same exon/intron structure in their downstream part while the structure of the RTKIV genes is very similar to that of RTKIII and FLT4. Both approaches are in complete agreement and indicate that RTKIII, IV, and V genes most probably evolved from a common ancestor already "in pieces" by successive duplications involving entire genes.

Alternative Splicing↗
PubMed1995

Gorilla and orangutan c-myc nucleotide sequences: inference on hominoid phylogeny.

The nucleotide sequences of the gorilla and orangutan myc loci have been determined by the dideoxy nucleotide method. As previously observed in the human and chimpanzee sequences, an open reading frame (ORF) of 188 codons overlapping exon 1 could be deduced from the gorilla sequence. However, no such ORF appeared in the orangutan sequence. The two sequences were aligned with those of human and chimpanzee as hominoids and of gibbon and marmoset as outgroups of hominoids. The branching order in the evolution of primates was inferred from these data by different methods: maximum parsimony and neighbor-joining. Our results support the view that the gorilla lineage branched off before the human and chimpanzee diverged and strengthen the hypothesis that chimpanzee and gorilla are more related to human than is orangutan.

Amino Acid Sequence↗
PubMed1995

Comparison of the cDNA and amino acid sequences of lipoprotein lipase in eight species.

By aligning nucleotide and amino acid sequences of lipoprotein lipase in eight species (man, pig, cow, sheep, mouse, rat, guinea-pig and chicken), we found that the main domains (catalytic, N-glycosylation and putative heparin binding sites) are well conserved. The longest identical amino acid chain was encoded by a sequence between the end of exon 2 and the beginning of exon 3, emphasizing the importance of this region which encodes the beta 5-loop of the active site, among other domains. Exon 10 is entirely untranslated in the seven mammals studied here and contains species-characteristic deletions, insertions or elements rich in A or A + T. In chicken, the beginning of exon 10 is translated. These eight previously unreported alignments could be a useful tool for further studies on LPL function.

Amino Acid Sequence↗
PubMed1994

A voltage-gated chloride channel in the yeast Saccharomyces cerevisiae.

We report the sequencing and identification on chromosome X of Saccharomyces cerevisiae of an open reading frame whose product, designated yClC-1, displays significant structural similarity to a voltage-gated Cl- channel family. This putative protein contains 13 hydrophobic domains very similar to transmembrane domains exhibited by known members of this family. Some amino acids in the domains and at the loops between them are well conserved among all members. This is the first voltage-gated Cl- channel described in the yeast S. cerevisiae. The identification of yClC-1 will facilitate the functional analysis of Cl- channels in general, and should also assist in the identification of other ClC genes in higher eukaryotes.

Amino Acid Sequence↗
PubMed1994

Genomic structure of the downstream part of the human FLT3 gene: exon/intron structure conservation among genes encoding receptor tyrosine kinases (RTK) of subclass III.

The FLT3 gene encodes a subclass-III receptor tyrosine kinase (RTKIII). We have determined the structural organization of the downstream part of the human FLT3 gene (also designated dsp-FLT3) that corresponds to the intracellular region of the protein. The coding region is spread over twelve exons spanning 10 kb of genomic DNA. Exon sizes range from 83 to 154 bp, while intron sizes range from 86 bp to more than 1.9 kb. Comparison with the corresponding domain of other RTKIII genes (KIT and FMS) shows that these genes share the same number of exons, which are highly conserved in size, sequence and exon/intron boundary positions. In addition, the intron phase of equivalent introns of FLT3, KIT and FMS are all identical. Our results reinforce our hypothesis based initially only on the KIT and FMS comparison showing that RTKIII genes share a common structural organization and have evolved from a common ancestor gene by cis and trans duplication. Comparison of the genomic organization of the intracellular-encoding part of RTKIII genes with that of RTKI, II and IV genes shows that subclasses III and IV are the most closely related.

Base Sequence↗
PubMed1994

A possible yeast homolog of human active-gene-repairing helicase ERCC6+.

We report here the sequencing and identification on the chromosome X of S. cerevisiae of an open reading frame, designated GTA1085, encoding a protein 1085 amino acids in size that displays significant homology to a of helicase subfamily. The highest similarity score is with ERCC6, a human putative helicase involved in the repair of active genes, with 53.3% identity over a stretch of 589 amino acids. This putative protein contains all seven consecutive domains conserved among DNA and RNA helicases. Thus, it apparently constitutes a novel member of this subfamily and might be involved, like ERCC6, in the preferential repair of active genes in yeast.

Amino Acid Sequence↗
PubMed1994

Revised nucleotide sequence of the COR region of yeast Saccharomyces cerevisiae chromosome X.

The COR region, a gene cluster located on chromosome X of Saccharomyces cerevisiae and including genes CYC1, UTR1, UTR3, OSM1, tRNA(Gly) and RAD7, was sequenced within the framework of the European Union genome systematic sequencing project. It was compared with previously published sequences to be found in GenBank under the acronym YSCCORA. While some of the discrepancies observed can be readily ascribed to polymorphism, others most probably result from sequencing errors. A revised version of the sequence of the COR cluster is given.

Base Sequence↗