Showing papers by "Jean-Louis Mandel published in 1987"

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.

Abstract: 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.

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

Abstract: 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.

Localization of the region homologous to the Duchenne muscular dystrophy locus on the mouse X chromosome

Abstract: Recent progress has resulted in part of the gene mutated in Duchenne and the milder Becker muscular dystrophies being cloned1–3 and has suggested that the gene itself extends over 1,000 to 2,000 kilobases (kb) (ref. 4). To study how mutations in this gene affect muscle development and integrity, it would be of interest to have available a mouse model of the human disease. The mouse mdx mutation affects muscle and confers a mild dystrophic syndrome, but it is not clear whether this mutation is equivalent to Duchenne/Becker muscular dystrophy in man5. Here we describe the use of two sequences from the human Duchenne muscular dystrophy (DMD) gene that cross-hybridize to mouse X-linked sequences to localize the gene homologous to DMD in the mouse. Both sequences map to the region of 10 centimorgan lying between the Tabby (Ta) and Stl4-l (DxPas8) loci, close to the phosphory-lase b kinase locus (Phk). By analogy with the human X-chromosome, we conclude that the region in the mouse around the G6pd and Stl4-l loci may contain two genes corresponding to distinct human myopathies: Emery Dreifuss muscular dystrophy which is known to be closely linked to Stl4-l in man6,7 and the DMD homologue described here.

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

Abstract: 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