Search PubMed⌕ Search

Biomedical subjects

J L Mandel

Publications and source records attributed to J L Mandel.

At least 181 records · Page 10Linked to original sources
PubMed1988

The chicken dystrophin cDNA: striking conservation of the C-terminal coding and 3' untranslated regions between man and chicken.

Dystrophin is a very large muscle protein (approximately 400 kd) the deficiency of which is responsible for Duchenne muscular dystrophy. Its function is unknown at present. In order to know whether different domains of the protein are differentially conserved during evolution, we have cloned and sequenced the chicken dystrophin cDNA. The protein coding sequence has almost the same size as in man. The N-terminal region that resembles the actin binding domain of alpha actinin, as well as the large spectrin like domain show 80% and 75% conservation respectively between chicken and man. In contrast, the C-terminal region shows 95% identity over 627 aa suggesting that it is an important region of interaction with other proteins. Comparison of the amino acid sequence of this C-terminal region to other protein sequences shows only marginally significant similarities. Finally we have found a striking conservation of three segments of the 3' untranslated sequence (85% homology over a total of 920 nt) between chicken and man. These also appear to be conserved in other mammals. This high conservation is not linked to open reading frames.

Amino Acid Sequence↗
PubMed1988

Chromosome localization and polymorphism of an oestrogen-inducible gene specifically expressed in some breast cancers.

The BCEI gene codes for a small secreted protein and is expressed in the human mammary tumour cell line MCF7 under oestrogen control and in some breast cancers. We have mapped the gene to chromosome 21 using a panel of somatic hybrid lines, and in situ hybridization has allowed a precise assignment to band 21q223. Two restriction fragment length polymorphisms (RFLP) are described that should be of use in linkage or population studies to test a possible involvement of the BCEI gene in genetic predisposition to breast cancer. This gene should also be a useful marker for the genetic and physical mapping of chromosome 21, and for a better definition of the region involved in the clinical phenotype of Downs syndrome.

Breast Neoplasms↗
PubMed1988

Multilocus analysis of the fragile X syndrome.

A multilocus analysis of the fragile X (fra(X] syndrome was conducted with 147 families. Two proximal loci, DXS51 and F9, and two distal loci, DXS52 and DXS15, were studied. Overall, the best multipoint distances were found to be DXS51-F9, 6.9%, F9-fra(X), 22.4%; fra(X)-DXS52, 12.7%; DXS52-DXS15, 2.2%. These distances can be used for multipoint mapping of new probes, carrier testing and counseling of fra(X) families. Consistent with several previous studies, the families as a whole showed genetic heterogeneity for linkage between F9 and fra(X).

Chromosome Mapping↗
PubMed1988

Genetic mapping of anhidrotic ectodermal dysplasia: DXS159, a closely linked proximal marker.

Three families with anhidrotic ectodermal dysplasia (AED) have been studied by linkage analysis with seven polymorphic DNA markers from the Xp11-q21 region. Previously reported linkage to DXYS1 (Xq13-q21) has been confirmed (z (theta) = 4.08 at theta = 0.05) and we have also established linkage to another polymorphic locus, DXS159, located in Xq11-q12 (z (theta) = 4.28 at theta = 0.05). Physical mapping places DSX159 proximal to the Xq12 breakpoint of an X autosome translocation found in a female with clinical signs of ectodermal dysplasia. Of all markers that have been used in linkage analysis of AED, DXS159 would appear the closest on the proximal side of the disease locus.

Chromosome Mapping↗
PubMed1988

Conservation and reorganization of loci on the mammalian X chromosome: a molecular framework for the identification of homologous subchromosomal regions in man and mouse.

By means of cross-reacting molecular probes, some 18 loci specific for the X chromosome of both man and mouse have been localized on the mouse X chromosome using an interspecific mouse cross involving the inbred SPE/Pas strain derived from Mus spretus. Comparison of the localizations of these loci on the mouse X with their positions on the human X chromosome suggests that intrachromosomal rearrangements involving at least five X chromosome breakage events must have occurred during the period of evolutionary divergence separating primates from rodents. Within the five blocks of chromosomal material so defined, there is for the moment little or no evidence that either chromosomal inversion events or extensive rearrangements have occurred. These data confirm the remarkable evolutionary conservation of the X chromosome apparent in mammalian species, compared to autosomal synteny groups in which both inter- and intrachromosomal rearrangement events appear to have occurred frequently. The breakage events described here for the X chromosome should therefore provide a minimal estimate for the frequency of chromosomal rearrangement events, such as breakage and inversion, which have affected autosomal synteny groups during the evolutionary period separating man from mouse. The definition of the number of chromosome breakage events by which the X chromosomes of these species differ, together with their localization, provides a framework for the use of interspecies mouse crosses for further detailed mapping of particular subchromosomal regions of the human X chromosome and for defining loci in the mouse homologous to those implicated in human congenital diseases.

Animals↗
PubMed1988

Isolation and characterization of a family of sequences dispersed on the human X chromosome.

During a systematic search for X-specific sequences we isolated a DNA fragment (called G1.3) that hybridizes to six further homologous X-specific genomic fragments that map to at least four different regions of the human X chromosome. Genomic segments of 11-30 kb (called G1.3 a, b, c, d, and e or DNF22S1 to DNF22S5) have been subsequently cloned for five of the seven repetitions and characterized by restriction mapping. Single-copy sequences have been used to analyze homology between cloned repetitions, to confirm X specificity, and to regionally localize the repetitions. Sequence homology between members of this family seems to be very high (80-90%) and to extend over at least 5 to 12 kb. In situ hybridization and Southern blotting experiments with a panel of human-rodent hybrid cell lines demonstrated that four of the cloned sequences map to three different regions within Xp21.2-pter and the fifth one (G1.3c) maps to Xq28. The family is present with the same complexity and X specificity in macaques (20-30 x 10(6) years divergence with man), whereas no related sequences were detected in the mouse. To our knowledge small families of dispersed chromosome-specific sequences have been described only for the human Y chromosome. The possible functional or evolutionary significance of this family is discussed.

Animals↗
PubMed1988

Genetic mapping of the Xq27-q28 region: new RFLP markers useful for diagnostic applications in fragile-X and hemophilia-B families.

We have characterized and genetically mapped new polymorphic DNA markers in the q27-q28 region of the X chromosome. New informative RFLPs have been found for DXS105, DXS115, and DXS152. In particular, heterozygosity at the DXS105 locus has been increased from 25% to 52%. We have shown that DXS105 and DXS152 are contained within a 40-kb region. A multipoint linkage analysis was performed in fragile-X families and in large normal families from the Centre d'Etudes du Polymorphisme Humain (CEPH). This has allowed us to establish the order centromere-DXS144-DXS51-DXS102-F9-DXS105-FRAX A-(F8, DXS15, DXS52, DXS115). DXS102 is close to the hemophilia-B locus (z[theta] = 13.6 at theta = .02) and might thus be used as an alternative probe for diagnosis in Hemophila-B families not informative for intragenic RFLPs. DXS105 is 8% recombination closer to the fragile-X locus than F9 (z[theta] = 14.6 at theta = .08 for the F9-DXS105 linkage) and should thus be a better marker for analysis of fragile-X families. However, the DXS105 locus appears to be still loosely linked to the fragile-X locus in some families. The multipoint estimation for recombination between DXS105 and FRAXA is .16 in our set of data. Our data indicate that the region responsible for the heterogeneity in recombination between F9 and the fragile-X locus is within the DXS105-FRAXA interval.

Chromosome Mapping↗
PubMed1987

A 230kb cosmid walk in the Duchenne muscular dystrophy gene: detection of a conserved sequence and of a possible deletion prone region.

A 230 kb genomic region from the Duchenne muscular dystrophy gene has been cloned in a cosmid walk, using an improved vector and by screening the same unamplified library for all steps. The region cloned surrounds the translocation breakpoint characterized by Worton et al and Ray et al, and overlaps by 70 kb the Pert region cloned by Monaco et al. We have identified a region of strong sequence conservation in mammals and chicken, and comparison of the homologous sequences in chicken and man has indicated the presence of two putative protein coding exons. Comparison with the sequence recently published by Koenig et al shows that only one is present in the Duchenne cDNA, and this raises the question of the functional significance of the other conserved sequence. Single copy probes and whole cosmids generated during this work have been used to analyse the corresponding region in Duchenne patients. Of five independant patients shown to be deleted for a probe 30 kb in 3' of the translocation breakpoint, three have the 5' endpoint of the deletion within a region of less than 20 kb, 100 kb away from the probe used to ascertain the deletion. This might suggest the presence of a region where deletions occur preferentially.

Amino Acid Sequence↗
PubMed1987

Close linkage of random DNA fragments from Xq 21.3-22 to X-linked agammaglobulinaemia (XLA).

Linkage analysis of 15 families affected by X-linked agammaglobulinaemia (XLA) showed close linkage with three probes located towards the centre of the long arm of the X chromosome. No cross-overs were found using pXG12 (DXS94) lod 6.6 or S21 (DXS17) lod 4.4. One cross-over was found with 19.2 (DXS3). This confirms and extends a previous linkage study (Kwan et al. 1986) which demonstrated linkage with S21 and 19.2. Of the families 14 were informative for either pXG12 or S21 and these probes should thus be of great diagnostic value. No evidence of heterogeneity was found in the XLA families but several cross-overs within this region were detected in a family with the X-linked hyper-IgM syndrome confirming this disease as a separate clinical entity.

Agammaglobulinemia↗
PubMed1987

Multipoint genetic mapping of the Xq26-q28 region in families with fragile X mental retardation and in normal families reveals tight linkage of markers in q26-q27.

The q26-q28 region of the human X chromosome contains several important disease loci, including the locus for the fragile X mental retardation syndrome. We have characterized new polymorphic DNA markers useful for the genetic mapping of this region. They include a new Bell restriction fragment length polymorphism (RFLP) detected by the probe St14-1 (DXS52) and which may therefore be of diagnostic use in hemophilia A families. A linkage analysis was performed in fragile X families and in large normal families from the Centre d'Etude du Polymorphisme Humain (CEPH) by using seven polymorphic loci located in Xq26-q28. This multipoint linkage study allowed us to establish the order centromere-DXS100-DXS86-DXS144-DXS51-F9-FRAX+ ++-(DXS52-DXS15). Together with other studies, our results define a cluster of nine loci that are located in Xq26-q27 and map within a 10 to 15 centimorgan region. This contrasts with the paucity of markers (other than the fragile X locus) between the F9 gene in q27 and the G6PD cluster in q28, which are separated by about 30% recombination.

Chromosome Mapping↗
PubMed1987

Genetic mapping of nine DNA markers in the q11----q22 region of the human X chromosome.

We have ordered nine polymorphic DNA markers within detailed map of the proximal part of the human X chromosome long arm, extending from band q11 to q22, by use of both physical mapping with a panel of rodent-human somatic hybrids and multipoint linkage analysis. Analysis of 44 families (including 17 families from the Centre d'Etude du Polymorphisme Humain) provided highly significant linkage data for both order and estimation of map distances between loci. We have obtained the following order: DXS1-DXS159-DXYS1-DXYS12-DXS3-(DXS94 , DXS178)-DXYS17. The most probable location of DXYS2 is between DXS159 and DXS3, close to DXYS1 and DXYS12. The high density of markers (nine loci within 30 recombination units) and the improvement in the estimation of recombination frequencies should be very useful for multipoint mapping of disease loci in this region and for diagnostic applications.

Chromosome Banding↗