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C Auffray

Publications and source records attributed to C Auffray.

At least 37 records · Page 2Linked to original sources
PubMed1997

Novel genes mapping to the critical region of the 5q- syndrome.

The 5q- syndrome is a myelodysplastic syndrome with specific hematological features and a good prognosis. Using molecular mapping techniques, we have previously defined the critical region of gene loss of the 5q- chromosome in the 5q- syndrome as the approximately 5-Mb region at 5q31-q33 flanked by the genes for FGF1 and IL12B. This region is completely represented by a series of overlapping YACs, and we are currently generating a transcription map with the aim of identifying the tumor-suppressor gene associated with the development of the 5q- syndrome. In this study two techniques have been used: first, the screening of full-length cDNA libraries with radiolabeled YACs and second, the mapping of chromosome 5-specific expressed sequence tags (ESTs) to a YAC contig. A 1-Mb YAC contig encompassing the CSF1R gene has been used to screen a fetal brain cDNA library, and this has resulted in the identification of two genes comprising one known gene previously localized to the region (ADRB2) and one known gene previously unlocalized. Six of 135 chromosome 5-specific ESTs were localized by PCR screening to the YAC contig mapping to the critical region of the 5q- syndrome. IMAGE cDNA clones for each of the six ESTs have been obtained. These seven (excluding ADRB2) newly assigned cDNA clones were subjected to further analysis. The expression patterns of each of the cDNA clones have been established in a range of human tissues, including bone marrow. Six of seven cDNAs are expressed in human bone marrow. Six of seven cDNAs have no known homology to any deposited human sequences, and one (C29) is dihydropyrimidinase-related protein-3, a member of a novel gene family. Genomic localization and expression patterns would suggest that these newly assigned cDNAs represent potential candidate genes for the 5q- syndrome.

Chromosome Deletion↗
PubMed1997

Construction of an integrated physical and gene map of human chromosome 20p12 providing candidate genes for Alagille syndrome.

Physical mapping and localization of eSTS markers were used to generate an integrated physical and gene map covering a approximately 10-Mb region of human chromosome 20p12 containing the Alagille syndrome (AGS) locus. Seventy-four STSs, 28 of which were derived from cDNA sequences, mapped with an average resolution of 135 kb. The 28 eSTS markers define 20 genes. Six known genes, namely CHGB, BMP2, PLCB1, PLCB4, SNAP, and HJ1, were precisely mapped. Among the genes identified, one maps in the smallest region of overlap of the deletions associated with AGS and could therefore be regarded as a candidate gene for Alagille syndrome.

Alagille Syndrome↗
PubMed1997

Mapping of 59 EST gene markers in 31 intervals spanning the human X chromosome.

The positioning of Expressed Sequence Tags (ESTs) constitutes an important step towards a functional map of the human genome, including candidate genes for human genetic disorders that have been localized by linkage analysis. We localized 59 ESTs on the human X chromosome, including 44 derived from infant brain and 15 from adult muscle cDNA libraries. Localizations by a somatic cell hybrid panel were refined for five cDNAs by mapping them in yeast artificial chromosome (YAC) contigs.

Animals↗
PubMed1997

New chicken Rfp-Y haplotypes on the basis of MHC class II RFLP and MLC analyses.

New chicken Rfp-Y haplotypes were determined by the use of restriction fragment length polymorphism (RFLP) and mixed lymphocyte culture (MLC) in four different chicken haplotypes, B15, B19, B21, B201. The RFLP polymorphism was mapped to the Rfp-Y system by the use of a subclone (18.1) which maps near a polymorphic lectin gene located in the Rfp-Y system and DNA from families with known segregation of the implicated RFLP polymorphism. For the first time it is shown that major histocompatibility complex class II genes in the Rfp-Y system have functional implications. Sequence information of the B1 domain of the proposed Rfp-Y haplotypes was obtained which supported the functional data.

Amino Acid Sequence↗
PubMed1997

Regional assignment of 64 human gene transcripts on chromosome 8.

A panel of somatic cell hybrids specific for human chromosome 8 was used to localize 64 expressed sequence-tagged site (ESTS) markers to six individual regions by PCR amplification. Nine ESTS correspond to 8 known human genes and 6 others show similarities with vertebrate genes, whereas the remaining 49 ESTS markers correspond to novel genes with no database similarities. These gene transcript markers will contribute to the developing physical and expression maps of chromosome 8, and to the search for candidate genes for various human diseases.

Animals↗
PubMed1996

A gene map of the human genome.

The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at http://www.ncbi.nlm.nih.gov/SCIENCE96/.

Amino Acid Sequence↗
PubMed1996

Regional localization of 192 genic markers on human chromosome 1.

A panel of somatic cell hybrids has been used to localize 192 novel eSTS markers to seven individual subregions of human chromosome 1. The positions of the breakpoints in each of these hybrids have been determined relative to the genetic linkage map of chromosome 1, and so the approximate locations of the genes from which the eSTS markers have been derived can be determined. Although the distribution of the eSTS markers is relatively random, 23% were assigned to the 1p34-p36 region. The hybrid mapping panel does not subdivide the 1q24-q44 region, which contains 36% of the eSTS markers. This analysis, therefore, provides a series of genic markers in which to search for candidates for a variety of human genetic disorders and recessive oncogenes mapped to the same relative position on the chromosome.

Chromosome Mapping↗
PubMed1996

Assignment of Rfp-Y to the chicken major histocompatibility complex/NOR microchromosome and evidence for high-frequency recombination associated with the nucleolar organizer region.

Rfp-Y is a second region in the genome of the chicken containing major histocompatibility complex (MHC) class I and II genes. Haplotypes of Rfp-Y assort independently from haplotypes of the B system, a region known to function as a MHC and to be located on chromosome 16 (a microchromosome) with the single nucleolar organizer region (NOR) in the chicken genome. Linkage mapping with reference populations failed to reveal the location of Rfp-Y, leaving Rfp-Y unlinked in a map containing >400 markers. A possible location of Rfp-Y became apparent in studies of chickens trisomic for chromosome 16 when it was noted that the intensity of restriction fragments associated with Rfp-Y increased with increasing copy number of chromosome 16. Further evidence that Rfp-Y might be located on chromosome 16 was obtained when individuals trisomic for chromosome 16 were found to transmit three Rfp-Y haplotypes. Finally, mapping of cosmid cluster III of the molecular map of chicken MHC genes (containing a MHC class II gene and two rRNA genes) to Rfp-Y validated the assignment of Rfp-Y to the MHC/NOR microchromosome. A genetic map can now be drawn for a portion of chicken chromosome 16 with Rfp-Y, encompassing two MHC class I and three MHC class II genes, separated from the B system by a region containing the NOR and exhibiting highly frequent recombination.

Animals↗
PubMed1996

Incorporation of 35 novel gene transcripts into the physical and genetic map of human chromosome 13.

A panel of somatic cell hybrids carrying a defined set of rearrangements involving chromosome 13 has been used to assign 35 novel gene transcripts regionally. The positions of the chromosome 13 breakpoints in each somatic cell hybrid have previously been defined relative to the Généthon genetic linkage map. As a result, the position of each gene transcript has been determined relative to both the physical and the genetic linkage maps. Analysis of the distribution of these gene transcripts indicates a slight overrepresentation toward locations on the distal long arm of chromosome 13, with no localizations noted in the 13q22-q31 region. Seven of these novel gene transcripts and the gene encoding small ribonucleoprotein U6 have been mapped to YACs known to contain Généthon microsatellite markers, thereby providing further sublocalization relative to the genetic map. The positioning the these gene transcripts within the genetic and physical maps provide candidate genes for disease loci that are being mapped to the same intervals on the chromosome.

Animals↗
PubMed1996

Integrated physical, genetic, and genic map covering 3 Mb around the human NGF gene (NGFB) at 1p13.

We have characterized 11 overlapping yeast artificial chromosomes (YACs) in the 1p13 region, 8 of them containing the human nerve growth factor (NGF) gene (HGMW-approved symbol NGFB). Sequence-tagged sites (STSs) corresponding to YAC extremities have been designed and used for chromosome assignment on a panel of monochromosomic somatic cell hybrids to check for YAC chimerism, in parallel with analyses by fluorescence in situ hybridization. Determination of end STS content and restriction mapping of the YACs led to the construction of a 3-Mb YAC contig. Four microsatellite markers from the Généthon collection and seven genes known to map to the 1p13 region have been ordered on the contig around the NGF gene. A new gene transcript from the Genexpress catalog has been localized on the contig. This work provides an integrated physical, genetic, and genic map of this chromosome 1 region. It constitutes a basis for determining the structure of the NGF gene and for further characterizing its genic environment.

Animals↗
PubMed1996

Synthetic CD4 exocyclic peptides antagonize CD4 holoreceptor binding and T cell activation.

We have developed peptide analogs to analyze precise human CD4 substructures involved in MHC class II binding. Forms of the complementarity determining-like regions (CDRs) of the D1 domain of human CD4 were reproduced as synthetic aromatically modified exocyclic (AME) analogs and tested for their ability to block CD4-MHC II interactions and T cell activation. The exocyclic derived from CDR3 (residues 82-89) of human CD4, which specifically associated with CD4 on the T cell surface to create a heteromeric CD4 complex, blocked IL-2 production and antagonized the normal function of the CD4 receptor. The approach of creating novel synthetic antagonistic receptor complexes may represent a new receptor specific pharmaceutical approach to modulate biological function.

Amino Acid Sequence↗
PubMed1996

A radiation hybrid map of the human genome.

We have developed a panel of whole-genome radiation hybrids by fusing irradiated diploid human fibroblasts with recipient hamster cells. This panel of 168 cell lines has been typed with microsatellite markers of known genetic location. Of 711 AFM genetic markers 404 were selected to construct a robust framework map that spans all the autosomes and the X chromosome. To demonstrate the utility of the panel, 374 expressed sequence tags (ESTs) previously assigned to chromosomes 1, 2, 14 and 16 were localized on this map. All of these ESTs could be positioned by pairwise linkage to one of the framework markers with a LOD score of greater than 8. The whole genome radiation hybrid panel described here has been used as the starting material for the Genebridge4 panel that is being made widely available for genome mapping projects.

Animals↗
PubMed1996

Novel gene transcripts preferentially expressed in human muscles revealed by quantitative hybridization of a high density cDNA array.

A set of 1091 human skeletal muscle cDNA clone inserts representing more than 800 human gene transcripts were spotted as PCR products at high density on nylon membranes. Replicas of the filters were hybridized in stringent conditions with 33P-radiolabeled cDNA probes transcribed from skeletal muscle poly(A)+ RNA. Hybridization signals were collected on phosphor screens and processed using a software specifically adapted for this application to identify and quantitate each spot. Parameters likely to influence the hybridization signal intensity were assessed to eliminate artifacts. Each clone was assigned to one of four intensity classes reflecting the steady-state level of transcription of the corresponding gene in skeletal muscle. Differential expression of specific gene transcripts was detected using complex cDNA probes derived from nine different tissues, allowing assessment of their tissue specificity. This made it possible to identify 48 novel gene transcripts (including 7 homologous or related to known sequences) with a muscle-restricted pattern of expression. These results were validated through the analysis of known muscle-specific transcripts and by Northern analysis of a subset of the novel gene transcripts. All these genes have been registered in the Genexpress Index, such that sequence, map, and expression data can be used to decipher their role in the physiology and pathology of human muscles.

Blotting, Northern↗
PubMed1996

Mapping of the genetically independent chicken major histocompatibility complexes B@ and RFP-Y@ to the same microchromosome by two-color fluorescent in situ hybridization.

The chicken MHC is organized in two genetically independent gene complexes B@ and RFP-Y@. Previous studies have shown the localization of the B@ complex on a small microchromosome. By using two-color fluorescent in situ hybridization, we demonstrate the localization of the RFP-Y@ complex to the same chromosome. A recombination hot spot between the two loci might account for their independent segregation.

Animals↗
PubMed1996

Molecular basis of T lymphocyte CD4 antigen functions.

The T cell surface antigen CD4 plays a pivotal role in the MHC class II-restricted response of specific T lymphocytes and serves as the major receptor of human immunodeficiency viruses (HIV). Recent studies have shown the high complexity of CD4 functions in physiological and pathological conditions. We report here a short review of recent developments in the field and discuss the structural features which regulate the functions mediated by the CD4 coreceptor in mature T lymphocytes.

Binding Sites↗