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ABSTRACT: Jacobsen syndrome is a haploinsufficiency disorder caused, most frequently by terminal deletion of part of the long arm of chromosome 11, with breakpoints in 11q23.3-11q24.2. Inheritance of an expanded p(CCG)n trinucleotide repeat at the folate-sensitive fragile site FRA11B has been implicated in the generation of the chromosome breakpoint in several Jacobsen syndrome patients. The majority of such breakpoints, however, map distal to this fragile site and are not linked with its expression. To characterize these distal breakpoints and ultimately to further investigate the mechanisms of chromosome breakage, a 40-Mb YAC contig covering the distal long arm of chromosome 11 was assembled. The utility of the YAC contig was demonstrated in three ways: (1) by rapidly mapping the breakpoints from two new Jacobsen syndrome patients using FISH; (2) by demonstrating conversion to high resolution PAC contigs after direct screening of PAC library filters with a YAC clone containing a Jacobsen syndrome breakpoint; and (3) by placing 23 Jacobsen syndrome breakpoints on the physical map. This analysis has suggested the existence of at least two new Jacobsen syndrome breakpoint cluster regions in distal chromosome 11.
Genome Research 02/1999; 9(1):44-52. · 13.61 Impact Factor
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ABSTRACT: Mouse/human somatic cell hybrids constitute a valuable resource for both genetic and physical mapping. In this report, we describe the production and characterization of a series of six monochromosomal hybrids generated by fusion of murine micro-cells with intact human recipient cells. The presence of each mouse chromosome was characterized by PCR analysis and the integrity of the mouse chromosome retained in the hybrids confirmed by fluorescence in situ hybridization (FISH) analysis.
Mammalian Genome 03/1997; 8(2):81-5. · 2.89 Impact Factor
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M Nemani,
G Linares-Cruz,
H Bruzzoni-Giovanelli,
J P Roperch,
M Tuynder,
L Bougueleret, D Cherif,
M Medhioub,
P Pasturaud,
V Alvaro, [......],
I Le Gall,
D Israeli,
J Dausset,
F Sigaux,
I Chumakov,
M Oren,
F Calvo,
R B Amson,
D Cohen,
A Telerman
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ABSTRACT: Developmentally regulated genes in Drosophila, which are conserved through evolution, are potential candidates for key functions in biological processes such as cell cycle, programmed cell death, and cancer. We report cloning and characterization of the human homologue of the Drosophila seven in absentia gene (HUMSIAH), which codes for a 282 amino acids putative zinc finger protein. HUMSIAH is localized on human chromosome 16q12-q13. This gene is activated during the physiological program of cell death in the intestinal epithelium. Moreover, human cancer-derived cells selected for suppression of their tumorigenic phenotype exhibit constitutively elevated levels of HUMSIAH mRNA. A similar pattern of expression is also displayed by the p21waf1. These results suggest that mammalian seven in absentia gene, which is a target for activation by p53, may play a role in apoptosis and tumor suppression.
Proceedings of the National Academy of Sciences 09/1996; 93(17):9039-42. · 9.68 Impact Factor
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M Nemani,
G Linares-Cruz,
H Bruzzoni-Giovanelli,
J P Roperch,
M Tuynder,
L Bougueleret, D Cherif,
M Medhioub,
P Pasturaud,
V Alvaro, [......],
I Le Gall,
D Israeli,
J Dausset,
F Sigaux,
I Chumakov,
M Oren,
F Calvo,
R B Amson,
D Cohen,
A Telerman
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ABSTRACT: Developmentally regulated genes in Drosophila, which are conserved through evolution, are potential candidates for key functions
in biological processes such as cell cycle, programmed cell death, and cancer. We report cloning and characterization of the
human homologue of the Drosophila seven in absentia gene (HUMSIAH), which codes for a 282 amino acids putative zinc finger
protein. HUMSIAH is localized on human chromosome 16q12-q13. This gene is activated during the physiological program of cell
death in the intestinal epithelium. Moreover, human cancer-derived cells selected for suppression of their tumorigenic phenotype
exhibit constitutively elevated levels of HUMSIAH mRNA. A similar pattern of expression is also displayed by the p21waf1.
These results suggest that mammalian seven in absentia gene, which is a target for activation by p53, may play a role in apoptosis
and tumor suppression.
Proceedings of the National Academy of Sciences 08/1996; 93(17):9039-9042. · 9.68 Impact Factor
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ABSTRACT: Familial juvenile nephronophthisis (NPH) is an autosomal recessive progressive tubulo-interstitial kidney disorder, responsible for 6-10% of end-stage renal failure in children, and is frequently associated with Leber amaurosis (termed Senior-Løken syndrome). The biochemical basis of NPH is unknown. We recently reported linkage of the purely renal form of NPH to three markers on chromosome 2. Our results also suggested the existence of genetic heterogeneity between NPH and SLS. To map this NPH gene more precisely, we have now tested the segregation of six new microsatellite markers and five additional families. Haplotype analyses show unequivocally that four NPH families are not linked to the chromosome 2 markers, although there are no clinical or pathological features discernible in these families that could separate them from the families linked to the chromosome 2 NPH locus (NPH1). This reveals genetic heterogeneity in the purely renal form of NPH. In situ hybridization of YAC clones isolated with two closely linked markers assigned the NPH1 region to 2q13. Furthermore, based on haplotype analysis and specific recombination events, the NPH1 gene has been placed between D2S293/D2S340 and D2S121, a genetic interval of about 5-7 cM.
Genomics 08/1994; 22(2):296-301. · 3.02 Impact Factor
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ABSTRACT: A yeast artificial chromosome (YAC) contig located in 6p23 and spanning roughly 2.5 Mb has been constructed from the content of 10 sequence tagged sites (STSs) for YAC clones in 66 yeast colonies. Nine of the STSs have been genetically mapped in CEPH families. The order of STSs mapped with the contig is consistent with that of the genetic map. The order of loci that did not recombine with each other on the genetic map was inferred from the contig. Various regions of the contig are covered by multiple YAC clones that complement observed STS deletions. The STS for the CAG repeat sequence contained in the gene for spinal cerebellar ataxia 1 (gene symbol SCA1) is localized in the contig. It is likely that this gene is located in 6p23. The frequency of chimeric YAC clones in this contig is 35%. Eleven yeast colonies were found to carry two or more YACs. YAC subclones from some of these colonies showed size variation, and for several subclones, evidence consistent with deletion of a sequence tagged site.
Genomics 08/1994; 22(2):388-96. · 3.02 Impact Factor
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ABSTRACT: Seven patients with acute leukemia and translocation involving band 11q23 have been studied by fluorescence in situ hybridization (FISH) using YAC probes spanning the HRX gene. While hybridization signal was split by translocation between the rearranged 11 and the partner chromosomes in five patients, only one signal on the derivative 11 was observed in two patients, one with t(9;11)(p21-22;q23) and the other with t(6;11)(q27;q23). Having shown that HRX was rearranged in these two cases, the distal part of 11q23 was investigated using other YACs containing markers for this region. This showed that a 600-700 kb deletion, distal to the HRX breakpoint cluster region, had occurred in the two cases. This study supports the notion that the 5' end of HRX is the important part in the chimeric genes resulting from 11q23 translocations and suggests that deletions of the 3' part are not uncommon.
Leukemia 05/1994; 8(4):578-86. · 9.56 Impact Factor
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ABSTRACT: Fluorescence in situ hybridization (FISH) to interphase nuclei was performed to order probes corresponding to bands 11q22-q23 where the ataxia-telangiectasia (AT) gene(s) have been located. Cosmid probes and one phage probe previously localized to this chromosome 11 region by FISH to metaphase chromosomes, were hybridized to interphase nuclei of the somatic cell hybrid J1a, which contains chromosome 11 as the only human chromosome. Two-color FISH was used with a centromeric reference probe marker. The following order was obtained: cen-D11S385 (CJ52.75)-CJ52.3-D11S384 (CJ52.193)-CJ52.114-D11S424 (CJ52.77)-D11S132-NCAM-D11S351 (CJ52.208)-tel. The validity of using the centromeric probe was illustrated by showing that a probe corresponding to 11p13 hybridized more closely to the centromere than a probe corresponding to 11q22-q23, and by using cosmids hybridized three by three.
Human Genetics 02/1994; 93(1):1-6. · 5.07 Impact Factor
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ABSTRACT: Pigmentation in mammals is under complex genetic control. Amongst the genes involved in this process, those encoding tyrosinase and the tyrosinase-related-proteins 1 and 2 have been well characterized and share a number of features. Recently, the murine tyrosinase-related-protein-2 gene was shown to encode dopachrome-tautomerase activity and was mapped to the slaty locus. Human tyrosinase and tyrosinase-related-protein-1 genes have been isolated and demonstrate a high degree of similarity with their murine counterparts. However, there has been limited data regarding the existence of a human homologue for tyrosinase-related-protein-2 and its relationship to the other tyrosinase-related proteins. In this study, we report the molecular isolation of a cDNA encoding a human homologue of the murine tyrosinase-related-protein-2/dopachrome tautomerase. We have characterized its expression in human melanocytic cells and have analyzed the relationship between dopachrome tautomerase and tyrosinase activities with the level of visible pigmentation in these cells. TYRP2 has been mapped to the chromosomal region 13q32, thus extending a region of synteny with mouse-chromosome 14.
European Journal of Biochemistry 02/1994; 219(1-2):127-34. · 3.58 Impact Factor
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ABSTRACT: Numerical chromosome abnormalities were studied in 17 acute lymphoblastic leukemias and one hyperdiploid acute myeloblastic leukemia by fluorescence in situ hybridization (FISH) using YAC clones specific to chromosomes 21 and 6. The results agreed well with cytogenetic findings. Hyperdiploid leukemias with more than 50 chromosomes usually had 4 copies of chromosome 21 and three of chromosome 6, while diploid and pseudodiploid cases were confirmed to have two copies of the two chromosomes. Interesting discrepancies were also observed. In one patient, trisomy 6 was detected by FISH but not by cytogenetics because of the probable inclusion of a chromosome 6 segment within a marker chromosome. The percentages of nuclei with 3 or 4 spots (chromosome 21) and three spots (chromosome 6) in hyperdiploid cells were significantly different in some patients, whereas they might be identical from cytogenetic data.
Genes Chromosomes and Cancer 11/1993; 8(2):98-103. · 3.31 Impact Factor
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ABSTRACT: A t(9;11)(q33;q23) has been detected by chromosome painting with chromosome 11- and chromosome 9-specific probes in blast cells of a child with acute monocytic leukemia. Using a YAC clone spanning the usual breakpoint region of translocations of acute leukemias, it was shown that the breakpoint was effectively within the same region of the band 11q23. This was confirmed by Southern blot studies that showed the localization of the translocation breakpoint between the 6th and 8th exons of the HRX gene. The implication of the HRX gene in t(9;11)(q33;q23) is a novel example of the diversity of translocations involving this gene in hemopoietic disorders. Sequencing DNA in the vicinity of the breakpoints should help to understand the reason of the localization of the recombination hot spot at band 11q23.
Comptes Rendus de l Académie des Sciences - Series III - Sciences de la Vie 08/1993; 316(7):692-7.
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ABSTRACT: By circumventing the need for metaphase preparations, fluorescent in situ hybridization (FISH) on interphase nuclei using chromosome-specific probes is a promising tool for the study of numerical chromosome aberrations not only in proliferating, but also in non-dividing cells. We analyzed 15 cases of monosomy-7-associated myeloid disorders with a biotinylated probe to the (peri)centromeric region of chromosome 7. Monosomy 7 was readily confirmed in all cases during active disease. In two patients only a minority of nuclei was monosomic, whereas cytogenetics had shown all metaphases to be missing one chromosome 7. FISH in one of them was able to identify a small marker chromosome as isolated pericentromeric region of chromosome 7. Minimal residual disease however could not be detected in three remission samples analyzed, as percentages of disomic nuclei were within the range of normal controls (96.8% 2.1%). In order to determine lineage involvement of the monosomic clone, a recent technique combining immunophenotyping and FISH (FICTION) was performed in one patient with AML after MPD. Monosomy 7 was found in virtually all myelomonocytic and erythroid cells (as discriminated by lineage-specific antibodies), in a part of CD34-positive precursor cells, but not in lymphocytes. We conclude that monosomy 7 in this patient is restricted to an early committed progenitor cell capable of erythroid and myelomonocytic differentiation.
Leukemia 04/1993; 7(3):384-91. · 9.56 Impact Factor
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ABSTRACT: Fluorescence in situ hybridization (FISH) is currently developed to analyse chromosomal abnormalities of hemopoietic malignancies in several ways: description of chromosomal rearrangements using specific probes or chromosome painting; delineation of chromosomal breakpoints with probes previously localized to chromosomal bands; hybridization to interphase nuclei to detect numerical changes and, now, some structural abnormalities. Examples of usefulness of FISH to study hemopoietic malignancies are given.
Nouvelle revue française d'hématologie 03/1993; 35(1):45-7.
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ABSTRACT: An Alu polymerase chain reaction (PCR) probe specific for chromosome 11 prepared from the somatic cell hybrid J1 was used to analyze karyotypes of eight patients with acute monocytic leukemia (AML-M5). Chromosome painting confirmed the t(9;11) in one patient and a der(1)t(1;6)t(6;11) in another and allowed the identification of a complex rearrangement involving chromosomes 9, 11, and 17, previously classified as del(11)(q23), in a third patient. An analysis of five patients with AML-M5 and a normal karyotype did not detect abnormalities of chromosome 11. The usefulness of chromosome painting combined with in situ hybridization with probes previously located on particular chromosomes is emphasized.
Genes Chromosomes and Cancer 03/1993; 6(2):107-12. · 3.31 Impact Factor
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ABSTRACT: Thirteen cosmid probes were mapped on the long arm of chromosome 11 between 11q22 and 11q24 by nonradioactive in situ hybridization. Starting with these localizations and those of other probes mapped to 11q23, four acute leukemias with translocations involving 11q23 were studied with the same method. The translocation breakpoints of the t(4;11)(q21;q23), t(6;11)(q27;q23), t(9;11)(p21-p22;q23), and t(11;19)(q23;p13) were confirmed to be distal to CD3D. The probe cC111-304 was proximal to the t(11;19) breakpoint while distal to the breakpoints of the other rearrangements. In view of the diversity of chromosomal abnormalities involving band 11q23, our finding extends the molecular heterogeneity of the breakpoint localization in leukemias with rearrangements involving 11q23.
Genes Chromosomes and Cancer 04/1992; 4(2):107-12. · 3.31 Impact Factor
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ABSTRACT: The gene encoding the type II (p75) tumor necrosis factor receptor (TNF-RII) has been localized on human chromosome 1, band 1p36.2 by nonradioactive in situ hybridization. The gene encoding the type I (p55) TNF-R, which is structurally homologous to the type II (p75) TNF-R, has been previously localized on chromosome 12 band 12p13. Thus, despite their probable common ancestry, the genes for the two TNF-Rs are localized on different chromosomes.
Human Genetics 10/1991; 87(5):623-4. · 5.07 Impact Factor
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Human Genetics 07/1991; 87(2):231-3. · 5.07 Impact Factor
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Current Opinion in Biotechnology 01/1991; 1(2):172-9. · 7.71 Impact Factor
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ABSTRACT: In situ hybridization was performed in a case of acute monoblastic leukemia (FAB type M5b) with a rearrangement of the long arm of chromosome 11. Cytogenetic analysis after R- and G-banding showed an apparent deletion of 11q with a breakpoint at 11q23, and a translocation t(6;11) was suspected in certain metaphases. In situ hybridization with a biotinylated cosmid probe hybridizing at 11q25 confirmed the translocation t(6;11)(q27;q23). Use of nonradioactive in situ hybridization techniques for more precise characterization of chromosomal rearrangements in malignant cells is emphasized.
Genes Chromosomes and Cancer 12/1990; 2(4):341-4. · 3.31 Impact Factor
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ABSTRACT: A technique for nonradioactive in situ hybridization on human metaphase chromosomes has been developed to localize human cosmid clones. The simple procedure using two fluorescent dyes (fluorescein and propidium iodide) allows the simultaneous identification of chromosomal R-bands and hybridization signal in a single screening of the slides. This technique has been used for rapid correlation of the genetic and physical map of chromosome 11q13-qter in the region of genes responsible for ataxia-telangiectasia and tuberous sclerosis.
Proceedings of the National Academy of Sciences 10/1990; 87(17):6639-43. · 9.68 Impact Factor
