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Jean Weissenbach - One of the best experts on this subject based on the ideXlab platform.
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autosomal dominant familial spastic paraplegia reduction of the fsp1 Candidate Region on chromosome 14q to 7 cm and locus heterogeneity
American Journal of Human Genetics, 1995Co-Authors: Suzana Gispert, Jean Weissenbach, R Damen, Thomas Voit, Thomas Klockgether, Friedmar Kreuz, N Santos, Jorg B Schulz, G Orozco, Georg AuburgerAbstract:Three large pedigrees of Germany descent with autosomal dominant {open_quotes}pure{close_quotes} familial spastic paraplegia (FSP) were characterized clinically and genetically. Haplotype and linkage analyses, with microsatellites covering the FSP Region on chromosome 14q (locus FSP1), were performed. In pedigree W, we found a haplotype that cosegregates with the disease and observed three crossing-over events, reducing the FSP1 Candidate Region to 7 cM; in addition, the observation of apparent anticipation in this family suggests a trinucleotide repeat expansion as the mutation. In pedigree D and S, the gene locus could be excluded from the whole FSP1 Region, confirming the locus heterogeneity of autosomal dominant FSP. 11 refs., 2 figs., 2 tabs.
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autosomal dominant familial spastic paraplegia is genetically heterogeneous and one locus maps to chromosome 14q
Nature Genetics, 1993Co-Authors: Jamile Hazan, De Recondo J, Arnold Munnich, Judith Melki, C Lamy, Jean WeissenbachAbstract:Autosomal dominant familial spastic paraplegia (FSP) is a degenerative disorder of unknown aetiology characterized by a progressive spasticity of the legs. Three families with autosomal dominant FSP of early onset were analysed in linkage studies using highly polymorphic microsatellite markers. Close linkage to a group of markers on chromosome 14q (maximum multipoint lodscore z=10) was observed in one family. This chromosome 14q Candidate Region was entirely excluded in the two other families, providing evidence of genetic heterogeneity within a homogeneous clinical form of FSP.
David N Louis - One of the best experts on this subject based on the ideXlab platform.
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transcript map of the 3 7 mb d19s112 d19s246 Candidate tumor suppressor Region on the long arm of chromosome 19
Cancer Research, 2002Co-Authors: Christian Hartmann, Loki Johnk, Gaspar Kitange, Linda K Ashworth, Robert B Jenkins, David N LouisAbstract:Allelic losses of the q13.3 Region of chromosome 19 have been documented in malignant gliomas, neuroblastomas, and ovarian carcinomas, strongly suggesting the presence of a 19q13.3 tumor suppressor gene. Deletion mapping in tumors over the past decade has narrowed the Candidate Region considerably but has produced partially conflicting results, with some small Candidate Regions defined only by isolated tumors with deletions. Mutation and expression screening of genes from the most likely Candidate Regions has failed to identify the gene of interest, perhaps because of the conflicting deletion mapping data. The recently increased public availability of human genomic sequence, combined with improved bioinformatics capabilities, has now made it possible to map much larger Candidate Regions in considerable detail. We have manually generated a transcript map that spans most of the 19q13.3 tumor suppressor Candidate Region, from D19S219 to D19S246, with a resolution and quality superior to that of computer-generated maps. These results are presented in the hope that an improved map of the Candidate Region will facilitate further widespread screening and eventual identification of the gene or genes deleted in human gliomas, neuroblastomas, and ovarian cancers.
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Common Regions of deletion on chromosome 22q12.3-q13.1 and 22q13.2 in human astrocytomas appear related to malignancy grade.
Journal of Neuropathology and Experimental Neurology, 1999Co-Authors: Jonathan S Silver, Lisa Blazejewski, Masao Matsutani, Andreas Von Deimling, Ryo Nishikawa, David N LouisAbstract:Approximately 30% of human astrocytomas have been reported to display allelic loss of the long arm of chromosome 22, suggesting the presence of a chromosome 22q astrocytoma suppressor gene. To define the most likely location for this putative tumor suppressor, we performed deletion mapping on 141 tumors using 16 chromosome 22q microsatellite markers. Allelic loss of 22q was observed in 2/12 (17%) of astrocytomas, 9/29 (31%) of anaplastic astrocytomas, and 38/100 (38%) of glioblastomas, consistent with a role for chromosome 22q loss in astrocytoma progression as well as formation. Twenty-two tumors exhibited allelic loss at every informative locus, consistent with loss of the entire arm of 22q. Twenty-seven tumors showed partial deletions, with one common Region of deletion at 22q12.3-q13.1 between markers D22S280 and D22S282, and a second Candidate Region at 22q13.2 near the marker D22S1170. For the proximal Candidate Region, the incidence of allelic loss was similar between grades; for the distal locus, the incidence increased with grade, raising the possibility that the distal locus is involved in a later stage of astrocytoma tumorigenesis.
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refined deletion mapping of the chromosome 19q glioma tumor suppressor gene to the d19s412 std interval
Oncogene, 1996Co-Authors: Jonathan E Rosenberg, Andreas Von Deimling, David K Lisle, Jennifer A Burwick, Keisuke Ueki, Harvey W Mohrenweiser, David N LouisAbstract:: Allelic loss of chromsome 19q occurs frequently in malignant gliomas, suggesting the presence of a chromosome 19q glioma tumor suppressor gene. Deletion mapping studies have delineated a 3.5 Mb Candidate Region between D19S219 and HRC. Cloned sequences from the proximal 425 kb of this interval, however, have not shown tumor-specific alterations. To refine the location of the tumor suppressor gene further, we conducted loss of heterozygosity studies on 191 malignant gliomas using nine PCR-based polymorphisms. These included the previously identified and physically mapped markers D19S219, DM, D19S112, HRC and the recently physically mapped polymorphisms at D19S412, STD, D19S596 and GYS. In addition, we isolated a novel microsatellite polymorphism that maps 400 kb telomeric to D19S112. Oligodendroglial tumors showed frequent loss of heterozygosity in all grades, and typically displayed allelic loss at all studied markers. Astrocytomas, however, showed frequent loss primarily in anaplastic astrocytomas and displayed deletion breakpoints within the Candidate Region. Deletion mapping revealed a minimal Region of overlap between D19S412 and STD, a distance of 900 kb. These data suggest that the D19S412-STD interval represents the most likely location for a chromsome 19q glioma tumor suppressor gene involved in astrocytoma, and perhaps oligodendroglioma, tumorigenesis.
Katsushi Tokunaga - One of the best experts on this subject based on the ideXlab platform.
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yac and cosmid contigs encompassing the fukuyama type congenital muscular dystrophy fcmd Candidate Region on 9q31
Genomics, 1997Co-Authors: Masashi Miyake, Yutaka Nakahori, Ikumi Matsushita, Kazuhiro Kobayashi, Kunihiko Mizuno, Momoki Hirai, Ichiro Kanazawa, Yasuo Nakagome, Katsushi Tokunaga, Tatsushi TodaAbstract:Fukuyama-type congenital muscular dystrophy (FCMD), the second most common form of childhood muscular dystrophy in Japan, is an autosomal recessive severe muscular dystrophy associated with an anomaly of the brain. We had mapped the FCMD gene to an approximately 5-cM interval between D9S127 and D9S2111 on 9q31-q33 and had also found evidence for linkage disequilibrium between FCMD and D9S306 in this Candidate Region. Through further analysis, we have defined another marker, D9S172, which showed stronger linkage disequilibrium than D9S306. A yeast artificial chromosome (YAC) contig spanning 3,5 Mb, which includes this D9S306-D9S172 interval on 9q31, has been constructed by a combination of sequence-tagged site, Alu-PCR, and restriction mapping. Also, cosmid clones subcloned from the YAC were assembled into three contigs, one of which contains D9S2107, which showed the strongest linkage disequilibrium with FCMD. These contigs also allowed us to order the markers as follows: cen-D9S127-(approximately 800 kb)-D9S306 (identical to D9S53)-(approximately 700 kb)-A107XF9-(approximately 500 kb)-D9S172-(approximately 30 kb)-D9S299 (identical to D9S774)-(approximately 120 kb)-WI2269-tel. Thus, we have constructed the first high-resolution physical map of the FCMD Candidate Region. The YAC and cosmid contigs established here will be a crucial resource for identification of the FCMD gene and other genes in this Region.
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yac and cosmid contigs encompassing the fukuyama type congenital muscular dystrophy fcmd Candidate Region on 9q31
Genomics, 1997Co-Authors: Masashi Miyake, Yutaka Nakahori, Ikumi Matsushita, Kazuhiro Kobayashi, Kunihiko Mizuno, Momoki Hirai, Ichiro Kanazawa, Yasuo Nakagome, Katsushi Tokunaga, Tatsushi TodaAbstract:Fukuyama-type congenital muscular dystrophy (FCMD), the second most common form of childhood muscular dystrophy in Japan, is an autosomal recessive severe muscular dystrophy associated with an anomaly of the brain. We had mapped the FCMD gene to an approximately 5-cM interval between D9S127 and D9S2111 on 9q31-q33 and had also found evidence for linkage disequilibrium between FCMD and D9S306 in this Candidate Region. Through further analysis, we have defined another marker, D9S172, which showed stronger linkage disequilibrium than D9S306. A yeast artificial chromosome (YAC) contig spanning 3.5 Mb, which includes this D9S306-D9S172 interval on 9q31, has been constructed by a combination of sequence-tagged site, Alu-PCR, and restriction mapping. Also, cosmid clones subcloned from the YAC were assembled into three contigs, one of which contains D9S2107, which showed the strongest linkage disequilibrium with FCMD. These contigs also allowed us to order the markers as follows: cen-D9S127-({approximately}800 kb)-D9S306 (identical to D9S53)-({approximately}700 kb)-A107XF9-({approximately}500 kb)-D9S172-({approximately}30 kb)-D9S299 (identical to D9S774)-({approximately}120 kb)-WI2269-tel. Thus, we have constructed the first high-resolution physical map of the FCMD Candidate Region. The YAC and cosmid contigs established here will be a crucial resource for identification of the FCMD gene and other genes in this Region. 37 refs., 7 figs., 2 tabs.
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linkage disequilibrium mapping narrows the fukuyama type congenital muscular dystrophy fcmd Candidate Region to 100 kb
American Journal of Human Genetics, 1996Co-Authors: Tatsushi Toda, Yusuke Nakamura, Masashi Miyake, Kazuhiro Kobayashi, Kunihiko Mizuno, Ichiro Kanazawa, Yasuo Nakagome, Kayoko Saito, Makiko Osawa, Katsushi TokunagaAbstract:Abstract Fukuyama-type congenital muscular dystrophy (FCMD), the second most common form of muscular dystrophy in Japan, is an autosomal recessive severe muscular dystrophy associated with brain anomalies. After our initial mapping of the FCMD locus to chromosome 9q31-33, we have further defined the locus within a approximately 5-cM Region between D9S127 and D9S2111 and have found linkage disequilibrium between FCMD and D9S306 in this Candidate Region on 9q31. The high prevalence of FCMD among the Japanese, who are a relatively isolated population, provides an opportunity to utilize linkage-disequilibrium mapping. We developed three new microsatellites, near D9S306, from the FCMD YAC contig, determined their positions on YACs, and performed linkage-disequilibrium mapping with these markers and other newly published loci. The maximum value of p(excess), which represents the strength of linkage disequilibrium, was obtained at D9S2107; and this value showed a relatively steady rise and fall across the Region that is likely to contain FCMD. Distances between FCMD and each marker were presumed to be approximately 1 Mb, approximately 350 kb, approximately 140 kb, approximately 20 kb, approximately 280 kb, approximately 450 kb, and approximately 740 kb for D9S306, A107XF9, D9S2105, D9S2107, D9S172, D9S299, and D9S2109, respectively. Haplotype analysis using the three closest markers D9S2105, D9S2107, and D9S172 indicated that most FCMD-bearing chromosomes are derived from a single ancestral founder and suggested that these markers can be used for the diagnosis of sporadic FCMD. Thus, the FCMD gene is most likely to lie within a Region of <100 kb containing D9S2107.
Judith Melki - One of the best experts on this subject based on the ideXlab platform.
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Mutations in DDR2 Gene Cause SMED with Short Limbs and Abnormal Calcifications
American journal of human genetics, 2008Co-Authors: Ruth Bargal, Judith Melki, Valérie Cormier-daire, Ziva Ben-neriah, Martine Le Merrer, Jacob Sosna, David Zangen, Sarah F. Smithson, Zvi Borochowitz, Ruth BelostotskyAbstract:The spondylo-meta-epiphyseal dysplasia [SMED] short limb-hand type [SMED-SL] is a rare autosomal-recessive disease, first reported by Borochowitz et al. in 1993.(1) Since then, 14 affected patients have been reported.(2-5) We diagnosed 6 patients from 5 different consanguineous Arab Muslim families from the Jerusalem area with SMED-SL. Additionally, we studied two patients from Algerian and Pakistani ancestry and the parents of the first Jewish patients reported.(1) Using a homozygosity mapping strategy, we located a Candidate Region on chromosome 1q23 spanning 2.4 Mb. The position of the Discoidin Domain Receptor 2 (DDR2) gene within the Candidate Region and the similarity of the ddr2 knockout mouse to the SMED patients' phenotype prompted us to study this gene(6). We identified three missense mutations c.2254 C > T [R752C], c. 2177 T > G [I726R], c.2138C > T [T713I] and one splice site mutation [IVS17+1g > a] in the conserved sequence encoding the tyrosine kinase domain of the DDR2 gene. The results of this study will permit an accurate early prenatal diagnosis and carrier screening for families at risk.
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autosomal dominant familial spastic paraplegia is genetically heterogeneous and one locus maps to chromosome 14q
Nature Genetics, 1993Co-Authors: Jamile Hazan, De Recondo J, Arnold Munnich, Judith Melki, C Lamy, Jean WeissenbachAbstract:Autosomal dominant familial spastic paraplegia (FSP) is a degenerative disorder of unknown aetiology characterized by a progressive spasticity of the legs. Three families with autosomal dominant FSP of early onset were analysed in linkage studies using highly polymorphic microsatellite markers. Close linkage to a group of markers on chromosome 14q (maximum multipoint lodscore z=10) was observed in one family. This chromosome 14q Candidate Region was entirely excluded in the two other families, providing evidence of genetic heterogeneity within a homogeneous clinical form of FSP.
Jamile Hazan - One of the best experts on this subject based on the ideXlab platform.
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autosomal dominant familial spastic paraplegia is genetically heterogeneous and one locus maps to chromosome 14q
Nature Genetics, 1993Co-Authors: Jamile Hazan, De Recondo J, Arnold Munnich, Judith Melki, C Lamy, Jean WeissenbachAbstract:Autosomal dominant familial spastic paraplegia (FSP) is a degenerative disorder of unknown aetiology characterized by a progressive spasticity of the legs. Three families with autosomal dominant FSP of early onset were analysed in linkage studies using highly polymorphic microsatellite markers. Close linkage to a group of markers on chromosome 14q (maximum multipoint lodscore z=10) was observed in one family. This chromosome 14q Candidate Region was entirely excluded in the two other families, providing evidence of genetic heterogeneity within a homogeneous clinical form of FSP.
