Biomedical subjects

C Petit

Publications and source records attributed to C Petit.

At least 163 records · Page 9Linked to original sources

PubMed1994

A human gene responsible for neurosensory, non-syndromic recessive deafness is a candidate homologue of the mouse sh-1 gene.

The identification of mouse models for the various forms of human neurosensory non-syndromic recessive deafness would constitute a major advance in the study of human deafness. Here we describe the localization of a human gene for neurosensory, nonsyndromic recessive deafness (NSRD2) to chromosome 11q13.5 by linkage analysis of a highly consanguineous family. A maximum lod score of 10.63 (theta = 0.018) was obtained for the microsatellite marker D11S527. Homozygosity mapping refined the localization of NSRD2 to a 6 cM interval also containing the olfactory marker protein (OMP) gene. The murine homologue of OMP is tightly linked to the autosomal recessive deafness gene sh-1. These results, and clinical data, suggest that NSRD2 is the human homologue of the mouse sh-1 gene.

Animals↗

PubMed1993

A cytokine receptor gene cluster in the X-Y pseudoautosomal region?

The receptors for interleukin-3 (IL-3), IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF) are heterodimers comprised of ligand specific alpha chains and a common beta chain. The genes encoding the IL-5 receptor alpha chain and the common beta chain reside on chromosome 3 and 22 respectively, while the GM-CSF receptor alpha chain gene (CSF2RA) has been mapped to the pseudoautosomal region (PAR) of the sex chromosomes, which is a 2.6-Mb stretch of homologous sequence at the tips of the short arms within which a single obligatory recombination occurs during male meiosis. We have mapped the gene encoding the IL-3 receptor alpha chain (IL3RA) to the sex chromosomes by polymerase chain reaction (PCR) analysis of human-mouse or human-chinese hamster cell hybrids, and to Yp13.3 and Xp22.3 using fluorescence in situ hybridization. To explore the possibility that IL3RA is located within the pseudoautosomal region we screened the Centre d'Etude du Polymorphisme Humain (CEPH) pedigrees for an informative-restriction fragment-length polymorphism (RFLP) that showed male meiotic recombination. Two informative CEPH pedigrees were identified that displayed this phenomenon, confirming the psuedoautosomal location of IL3RA. Using long-range restriction mapping we have found that IL3RA maps to the same 190-kb restriction fragment as CSF2RA, suggesting that a cytokine receptor gene cluster may reside in the PAR.

Base Sequence↗

PubMed1993

Expression of the KAL gene in multiple neuronal sites during chicken development.

The human KAL gene is responsible for the X chromosome-linked Kallmann syndrome. A partial cDNA sequence from the chicken KAL homologue was determined and used to study expression of the KAL gene, by in situ hybridization, during chicken development, from day 6 of incubation. The KAL gene is mainly expressed in neurons of the central nervous system during the second half of embryonic life. High levels of transcript were detected in mitral neurons of the olfactory bulbs, in striatal neurons, in Purkinje cells of the cerebellum, in retinal neurons, and in isolated neurons of the brainstem and spinal cord. No expression was observed in glial cells. A low level of expression was observed in some mesenchymal derivatives. In the adult, expression is maintained or increased in several neuronal populations, especially in optic tectum and striatum. A possible role for the KAL protein in synaptogenesis at these stages is discussed. These results in the chicken embryo help to elucidate the mechanisms of anosmia and gonadotropin-releasing hormone deficiency, which define Kallmann syndrome. In addition, most of the occasional symptoms described in Kallmann syndrome patients, such as cerebellar ataxia, abnormal ocular movements, abnormal spatial visual attention, mirror movements, and renal aplasia, could be ascribed to malfunction of areas that, in the chicken, express the KAL gene.

Amino Acid Sequence↗

PubMed1993

Absent chondrodysplasia punctata in a male with an Xp terminal deletion involving the putative region for CDPX1 locus.

This is a follow-up report on a male patient with a 46,Y,r(X) karyotype. Although he had no clinico-radiological features of X-linked recessive chondrodysplasia punctata (CDPX1), molecular studies revealed an Xp terminal deletion involving the putative region for the CDPX1 locus (PABX-DXS31). We suspect that the absence of CDPX1 may be attributable to the nature of the disease and the extreme short stature of the patient (mean -5.6 S.D.).

Blotting, Southern↗

PubMed1993

Characterization and chromosomal assignment of a human cDNA encoding a protein related to the murine 102-kDa cadherin-associated protein (alpha-catenin).

We report the characterization of a human cDNA encompassing the complete coding region of a 945-residue putative protein (CAP-R) 80% identical to the recently described murine 102-kDa alpha-catenin (CAP102). The CAP-R protein mostly differs from CAP102 by the presence of a 48-residue insert. This insert exhibits similarity with a segment of the type 1 neurofibromatosis gene product. The analysis of a publicly available human "expressed sequence tag" collection revealed the existence of another human cDNA more closely related (89% identical) to CAP102. This strongly suggests that CAP-R is not the human homologue of the murine 102-kDa alpha-catenin but a new closely related gene of the vinculin family. This is further supported by the computed mutation rates falling outside the range observed for mammalian orthologous genes. Using in situ hybridization, the CAP-R gene could be mapped to the p11.1-p12 region of human chromosome 2 and to the homologous B3-D region of mouse chromosome 6.

Amino Acid Sequence↗

PubMed1993

A human pseudoautosomal gene encodes the ANT3 ADP/ATP translocase and escapes X-inactivation.

We report that the human ANT3 ADP/ATP translocase gene is a pseudoautosomal gene located proximal to the GM-CSF receptor alpha chain gene (CSF2RA). An ANT3-homologous locus, likely corresponding to a pseudogene, maps to chromosome 9. The ANT3 gene is transcribed from the centromere to the telomere and contains in its first intron a CpG island mapped 1300 kb from the telomere. This gene is transcribed from the Y chromosome and from the active and inactive X chromosomes. This gene thus escapes X-inactivation as predicted for genes belonging to the pseudoautosomal region.

Aneuploidy↗

PubMed1993

Characterization of the chicken and quail homologues of the human gene responsible for the X-linked Kallmann syndrome.

The human KAL gene, responsible for the X-linked Kallmann syndrome, was isolated previously. Southern blot analysis using human cDNA probes detected cross-hybridization with DNA from several organisms, including chicken and quail. The entire coding sequences of chicken and quail KAL cDNAs were determined. A comparison of these cDNAs with the human KAL cDNA reveals an overall identity of 73 and 72%, respectively. This results in 76 and 75% identity at the protein level. The highest conservation was found in the WAP four-disulfide core motif and in two of the four fibronectin type III repeats reported in the human protein. These results further support the hypothesis that the KAL protein is an extracellular matrix component with anti-protease and adhesion functions.

Amino Acid Sequence↗

PubMed1993

A 45,X male with an X;Y translocation: implications for the mapping of the genes responsible for Turner syndrome and X-linked chondrodysplasia punctata.

In a male patient with a 45,X karyotype, the terminal part of the Y chromosome short arm was translocated as a single block on to the X chromosome. This rearranged X chromosome was, in every regard, the same as that present in XX males resulting from an abnormal X-Y interchange. Correlations between the phenotype of this patient and the extent of the deletions on the X and Y chromosomes allowed us to map the genes responsible for most features of the Turner syndrome between DXS432 and Xqter on the X chromosome, and the homologous Y genes either on Yp in interval 4 or on Yq. The molecular analysis of this X-Y translocation allowed us also to reduce the interval for the X-linked recessive chondrodysplasia punctata gene to a 1.5 Mb interval between DXS432 and DXS31.

Adolescent↗

PubMed1993

Heterogeneity in the mutations responsible for X chromosome-linked Kallmann syndrome.

Kallmann syndrome represents the association of hypogonadotropic hypogonadism with anosmia. Three modes of transmission, X chromosome-linked, autosomal recessive and autosomal dominant, have been described. The KAL gene, responsible for the X-linked form of the disease, has been isolated and its intron-exon organization recently determined. We have searched for mutations of the KAL gene in 21 unrelated males affected by familial Kallmann syndrome. In these families, segregation of the disease was suggestive of the X-linked mode of transmission. In 2 families, large Xp22.3 deletions, both including the entire KAL gene, have been detected by Southern blot analysis. Here we report the sequence analysis of the entire coding region of the KAL gene in the 19 remaining patients. The approach consisted of sequencing each of the 14 coding exons and splice site junctions. Each exon was amplified by PCR on the genomic DNA, using oligonucleotides from the flanking intronic sequences as specific primers. Nine point mutations were identified at separate locations in four exons and one splice site, providing strong evidence for heterogeneity in mutations responsible for the X-linked Kallmann syndrome. In addition, the high frequency of unilateral renal aplasia in X-linked Kallmann patients (6 out of 11 males with identified alterations of the KAL gene) should be emphasized.

Amino Acid Sequence↗

PubMed1993

Five skeletal myosin heavy chain genes are organized as a multigene complex in the human genome.

Myosin heavy chain (MyHC) isoforms are encoded by a multigene family in vertebrates. We used genomic DNA mapping by pulse field gel electrophoresis to demonstrate that, in humans, the embryonic, fetal, fast IIB and IIX MyHC genes and a gene coding for a non-identified striated muscle MyHC fast-type isoform (NI), are contained within a 320 kb SalI genomic fragment. The locus is flanked by two CpG islands, separated by 580 kb. In order to further characterize the MyHC genes, a human genomic library constructed in yeast artificial chromosomes (YAC) was screened and five independent clones were isolated. Characterization of these YACs revealed that one of them contains at least five MyHC genes, based on partial sequencing of their conserved third coding exons. Three of these genes correspond to those encoding the embryonic, fetal and fast IIB MyHC isoforms. Moreover, in this YAC clone the embryonic and fetal genes, on the one hand, and the adult fast (IIB, IIX and NI) genes, on the other hand, are contained within two different ClaI fragments. This result suggests that the genes encoding the two developmental forms are adjacent in the human genome and that temporal regulation of the MyHC genes might be related to their organization within the locus. These data represent the first direct evidence for the existence in the human genome of a MyHC multigene locus that contains at least five genes.

Amino Acid Sequence↗

PubMed1993

Characterization of dinY, a new Escherichia coli DNA repair gene whose products are damage inducible even in a lexA(Def) background.

Bacteriophage Mu dX(Ap lac) was used to isolate a mutation in an Escherichia coli lexA(Def) strain representing a previously undescribed gene (dinY) which does not seem to be under the direct control of LexA. The insertion created a dinY::lacZ fusion in which beta-galactosidase expression required a DNA-damaging treatment (UV irradiation or mitomycin) and activable RecA protein. This strain showed a decreased Weigle reactivation of bacteriophage lambda. However, it was fully inducible for UV mutagenesis. Two-dimensional gel electrophoresis analysis identified two spots absent in the mutant which were both UV inducible only in the presence of activated RecA protein (RecA*). This finding suggests that the dinY::lacZ fusion lies in a gene either that is under the direct control of activated RecA or whose product undergoes RecA*-dependent posttranscriptional/posttranslational modification(s). The dinY gene may also control the expression of some other gene(s) and/or lie in an operon. The fusion was mapped at a position between 41 and 41.5 min on the E. coli chromosome, in the vicinity of the ruv operon.

Bacterial Proteins↗

PubMed1993

Xp22.3 deletions in isolated familial Kallmann's syndrome.

Several familial cases of Kallmann's syndrome (KS) have been reported, among which the X-chromosome-linked mode of inheritance is the most frequent. The gene responsible for the X-linked KS has been localized to the terminal part of the X-chromosome short arm (Xp22.3 region), immediately proximal to the steroid sulfatase gene responsible for X-linked ichthyosis. Large deletions of this region have been previously shown in patients affected with both X-linked ichthyosis and KS. We report here the search for Xp22.3 deletions in 20 unrelated males affected with isolated X-linked KS. Only 2 deletions were found using Southern blot analysis, indicating that large deletions are uncommon in patients affected with KS alone. Both deletions were shown to include the entire KAL gene responsible for X-linked KS. The patients carrying these deletions exhibit additional clinical anomalies, which are discussed: unilateral renal aplasia, unilateral absence of vas deferens, mirror movements, and sensory neural hearing loss.

Adolescent↗

PubMed1992

Physical mapping of 14 new DNA markers isolated from the human distal Xp region.

We have isolated 14 new DNA markers from the human Xpter-Xp21 region distal to the Duchenne muscular dystrophy gene by targeted cloning, employing two somatic cell hybrids containing this region as their sole human material. High-resolution physical localization of these markers within this region was obtained by hybridization to two mapping panels consisting of DNA from patients carrying various translocations and deletions in distal Xp. Five markers were assigned to the pseudoautosomal region where their position on the long-range map of this region was further determined by pulsed-field gel electrophoresis. The other nine markers map to the X-specific region. Informative TaqI restriction fragment length polymorphisms were observed for four loci. One of these represents a region-specific low-copy repeated element. These 14 new markers represent useful tools for the understanding of distal Xp deletion and translocation mechanisms and for the positional cloning of disease genes in the region.

Blotting, Southern↗

PubMed1992

Structure of the X-linked Kallmann syndrome gene and its homologous pseudogene on the Y chromosome.

The gene for the X-linked Kallmann syndrome (KAL), a developmental disorder characterized by hypogonadotropic hypogonadism and anosmia, maps to Xp22.3 and has a homologous locus, KALP, on Yq11. We show here that KAL consists of 14 exons spanning 120-200 kilobases that correlate with the distribution of domains in the predicted protein including four fibronectin type III repeats. The KALP locus reveals several large deletions and a number of small insertions, deletions and base substitutions which indicate it is a non-processed pseudogene. The sequence divergence between KAL and KALP in humans, and the chromosomal location of KAL homologous sequences in other primates, suggest that KALP and the steroid sulphatase pseudogene on Yq11 were involved in the same rearrangement event on the Y chromosome during primate evolution.

Amino Acid Sequence↗

PubMed1992

Chromosomal localisation of a pseudoautosomal growth gene(s).

Although recent molecular studies in patients with sex chromosome aberrations are consistent with a growth gene(s) being present in the pseudoautosomal region (PAR), the precise location has not been determined. In this report, we describe a Japanese boy and his mother with an interstitial deletion in Xp22.3 and review the correlation between genotype and stature in six cases of partial monosomy of the PAR. The results indicate that the region from DXYS20 to DXYS15 is the critical region for the putative growth gene(s).

Abnormalities, Multiple↗

PubMed1992

Evidence for a pseudoautosomal locus for schizophrenia. II: Replication of a non-random segregation of alleles at the DXYS14 locus.

Because of an association between sexual aneuploidies and schizophrenia, and because schizophrenic siblings have been found to be more often of the same than of the opposite sex, the susceptibility locus for schizophrenia is thought to lie within the pseudoautosomal region of the sex chromosomes. We analysed 33 sibships comprising 18 pairs, 13 trios, and 2 quartets of affected siblings, and found support for non-random segregation of of alleles at the DXYS14 locus in affected siblings. These findings are consistent with the pseudoautosomal hypothesis for schizophrenia and favour a genetic linkage between DXYS14 and the disease.

Alleles↗

PubMed1992

Secretion of macrophage cytotoxic factors induced by new desmuramyl acylpseudopeptide analogs of muramyl dipeptide.

Sixteen desmuramyl analogs of muramyl dipeptide (MDP) were tested for their abilities to stimulate cytotoxic factor secretion by mouse peritoneal macrophages. Among them, the pseudohexapeptide Boc-Gly psi [CH2O]-D-Ala-Ala-D-Glu[Lys(H-Gly)NHEt]-NH2 appeared to be four times more effective than MDP. From this study, the D configuration of the pseudo-alanyl (or lactyl) residue appears to be essential for activity.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1992

Short stature in a girl with a terminal Xp deletion distal to DXYS15: localisation of a growth gene(s) in the pseudoautosomal region.

This report describes a Japanese girl with short stature and a rearranged X chromosome. Her height remained below the 3rd centile growth curve for Japanese girls, and her predicted adult height (148.5 cm) was below her target height (163 cm) and target range (155 to 171 cm). Cytogenetic studies showed that the rearranged X chromosome was formed by a breakage at q26 and a transfer of the Xq fragment onto the tip of Xp. The abnormal X was always late replicating. No mosaicism was detected. Molecular analysis showed an Xp terminal deletion distal to DXYS15. Biochemical and radiological studies for short stature disclosed no abnormality. On the basis of height analysis of previous reports and a genotype-phenotype correlation of this patient, we propose that a growth gene(s) is present in the distal part of the pseudoautosomal region.

Blotting, Southern↗