Biomedical subjects
Publications and source records attributed to J F Mattei.
Using a rat cDNA probe encoding for the C-terminal extension of the large neurofilament subunit (NF-H), we have assigned, by in situ hybridization, the human NF-H gene to the q121-q131 region of chromosome 22. This localization may have implications in neurological diseases such as meningioma where a recessive locus involved in oncogenesis is located within this region.
A new case of recurrent achondroplasia in sibs of normal parents is reported. Two sisters and a half sister were affected. Various mechanisms can be postulated to account for unexpected recurrence of achondroplasia in the same sibship. Germinal mosaicism and unstable premutation are discussed here.
27 cases in which apparent balanced chromosomal rearrangements (reciprocal and translocations and pericentric inversions) are associated with phenotypic abnormalities are reported and compared with the previous published cases. Almost all patients display mental retardation and a non specific dysmorphism. Genetic counseling is different whether the abnormality is inherited or de novo. When an unexpected structural rearrangements is found in fetal cells, the attitude depends on the results of the parent's chromosomal study.
We report the identification of a new RFLP detected by the DNA probe MN12, which is linked to both the fragile site on the X chromosome at Xq27.3 and the highly polymorphic locus detected by St14 (DXS52). In situ mapping confirms the localisation of MN12 distal to the fragile site. A detailed physical analysis of this region of the X chromosome using pulsed-field gel electrophoresis has shown that MN12, St14 and DX13 (DXS15) are physically linked within a region of 470kb. A long range restriction map around the MN12 locus reveals at least two candidate HTF islands, suggesting the existence of expressed sequences in this region.
In spite of the large amount of genetic data obtained on the X chromosome and of the availability of many cloned sequences little is known about the physical map of this chromosome. The construction of large-scale restriction maps is now possible with pulsed field gel methods and data has recently been obtained in the region of band Xq28. We present here results of physical mapping in the Xq27 region, i.e. proximal to the fragile site at Xq27.3 associated with mental retardation, and show physical linkage between the coagulation factor IX gene and the mcf.2 transforming sequence recently localized to Xq27. Our data also indicate partial methylation of some sites in this region, and locate several 'HTF islands', i.e. CpG-rich, unmethylated sequences, containing several sites for 'rare cutter' enzymes, which are believed to be associated with expressed 'housekeeping' genes.
A new case of total monosomy 21 in a newborn is described. The diagnosis was first made using the cytogenetic data; it was then confirmed by the dosage of copper-superoxide dismutase (SOD-1) which showed a 50% decrease. In situ hybridization with a probe previously assigned to chromosome 21 was used to rule out the possibility of a partial monosomy with an unbalanced reciprocal translocation.
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A complementary cDNA clone (900 bp) representing the 3' untranslated region and almost the entire coding sequence of the human erythrocyte membrane glycophorin C has been used to determine the chromosomal location of the blood group Gerbich locus by in situ hybridization. The results indicate that this locus is assigned to the region q14-q21 of chromosome 2.
Recombinant plasmid clone p23 containing the cDNA proteolipid (PLP) sequence was localized by in situ hybridization on band q22 of the human X chromosome. This localization may have implications for X-linked demyelination diseases such as Pelizaeus-Merzbacher disease in man.
A cDNA probe corresponding to mRNA encoding human uroporphyrinogen decarboxylase (URO-D) was used to determine the chromosomal localization of the URO-D gene in the human genome. In agreement with previous studies, we have found that the locus for URO-D is located on chromosome 1 in hybrid cell mapping panels. The use of in situ hybridization allowed us to map the URO-D locus to band 1p34.
cDNA clones containing sequences coding for the murine neural cell adhesion molecule (N-CAM) were used in Southern hybridizations on human genomic DNA and demonstrated approximately 90% homology between human and murine NCAM genes. In situ hybridization with one of these clones was performed on human metaphase chromosomes and allowed the localization of the human NCAM gene to band q23 of chromosome 11. The genes for two other cell surface molecules believed to be involved in cell-cell interactions, Thy-1 and the delta chain of the T3-T cell receptor complex, have recently been localized to the same region of chromosome 11 in man. Moreover, this region of the human chromosome 11 appears to be syntenic to a region of murine chromosome 9 that also contains the staggerer locus: staggerer mice show abnormal neurological features which may be related to abnormalities in the conversion of the embryonic to the adult forms of the N-CAM molecule.
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One of the commonest forms of X-linked mental retardation is associated with a fragile site at Xq27 on the human X chromosome which can be visualised structurally after culturing cells in folate-deficient media. Unusually, the mutation can be transmitted through a phenotypically normal male. There is already some evidence that the gene loci for G6PD and factor IX are linked to this mental retardation locus. We have followed the inheritance of a DNA sequence 52A, in fragile site families that are also informative for factor IX. We demonstrate that these probes are localised at Xq27/Xq28-Xqter, close physically to the fragile site. We did not find close linkage between 52A, factor IX, and the fragile site in the families studied despite 52A and factor IX showing linkage in normal families. We discuss the importance of these data for the genetic mapping of this region of the human X chromosome and the implication for the use of these DNA probes for clinical diagnosis.
The coagulation factor IX gene and two other polymorphic loci corresponding to DNA probes 52 A and St 14 have been previously localized in the q27 to qter region of the human X chromosome. In order to study their localization with respect to the fragile site at Xq27-28, we have hybridized the three DNA probes to metaphase chromosomes of a boy with fragile X mental retardation. We show that probe 52 A is located in the proximal part of the Xq27 band, while the coagulation factor IX gene is on the distal part of this band, but proximal to the fragile site. The very polymorphic St 14 probe is located in the distal part of the Xq28 band, on the other side of the fragile site.
Recombinant plasmid clone B74 (also named D18 S3) containing a human single-copy DNA segment of 6 kilobases (kb) was localized by in situ hybridization on band p113 of chromosome 18. This probe was then used in cytogenetic diagnosis to identify precisely a small supernumerary chromosome as an isochromosome i(18p).
We report here four cases of unbalanced chromosomal rearrangements involving partial monosomies and trisomies of chromosome 7. The quantitative expression of diaphorase 2 (DIA-2), beta-glucuronidase (GUS-beta) and argino-succinate-lyase (ASL) were measured in these patients and compared with controls. The results suggest that the DIA-2 locus is in the band 7p221----q21, the GUS-beta locus in the band 7p22----q21 and the ASL locus in the band 7p221----q22.
Copper superoxide dismutase (Cu-SOD or SOD-1) was measured by radioimmunoassay (RIA) in amniotic cells and fluid as well as in fetal trisomy 21 fibroblasts. The significant increase of the SOD-1 activity observed in amniotic cells and fetal trisomy 21 fibroblasts demonstrates the early physiopathogenic expression of the supernumerary chromosome 21 in affected patients.