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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, N Santos, R Damen, Thomas Voit, Jorg B Schulz, Thomas Klockgether, G Orozco, Friedmar Kreuz, 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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The gene for Machado–Joseph disease maps to the same 3-cM interval as the spinal cerebellar ataxia 3 gene on Chromosome 14q
Neurobiology of Disease, 1994Co-Authors: Giovanni Stevanin, Alexandra Durr, Jean Weissenbach, P S Sousa, Geraldine Cancel, O Dubourg, Garth A Nicholson, E Jardim, Y Agid, E CassaAbstract:Abstract Machado–Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder in families of Portuguese–Azorean ancestry. The gene responsible for MJD has been assigned to a 29-cM interval on Chromosome 14q. A large Brazilian family with MJD was genotyped with six new microsatellite markers spanning 19 cM on Chromosome 14q. Linkage analysis and haplotype reconstruction reduced the MJD candidate region to a 3-cM interval between markers D14S280 and D14S81, permitting positional cloning. This interval also contains the spinal cerebellar ataxia 3 ( SCA3 ) gene, responsible for a genetic subtype of the type I autosomal dominant cerebellar ataxias, clinically related to MJD. This result supports the hypothesis that abnormalities in the same gene may be responsible for both disorders. The minor clinical differences between the two diseases may result from allelic heterogeneity.
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the gene for machado joseph disease maps to the same 3 cm interval as the spinal cerebellar ataxia 3 gene on Chromosome 14q
Neurobiology of Disease, 1994Co-Authors: Giovanni Stevanin, Alexandra Durr, Jean Weissenbach, P S Sousa, Geraldine Cancel, O Dubourg, Garth A Nicholson, E Jardim, Y Agid, E CassaAbstract:Abstract Machado–Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder in families of Portuguese–Azorean ancestry. The gene responsible for MJD has been assigned to a 29-cM interval on Chromosome 14q. A large Brazilian family with MJD was genotyped with six new microsatellite markers spanning 19 cM on Chromosome 14q. Linkage analysis and haplotype reconstruction reduced the MJD candidate region to a 3-cM interval between markers D14S280 and D14S81, permitting positional cloning. This interval also contains the spinal cerebellar ataxia 3 ( SCA3 ) gene, responsible for a genetic subtype of the type I autosomal dominant cerebellar ataxias, clinically related to MJD. This result supports the hypothesis that abnormalities in the same gene may be responsible for both disorders. The minor clinical differences between the two diseases may result from allelic heterogeneity.
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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, C Lamy, Judith Melki, Arnold Munnich, De Recondo J, 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.
Federico A Monzon - One of the best experts on this subject based on the ideXlab platform.
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Chromosome 14q loss defines a molecular subtype of clear cell renal cell carcinoma associated with poor prognosis
Modern Pathology, 2011Co-Authors: Leif E Peterson, Nizar M Tannir, Federico A Monzon, Karla Alvarez, Luan D. Truong, Robert J. Amato, Anil V. Parwani, Joan Hernandezmcclain, Eric JonaschAbstract:Loss of Chromosome 14 has been associated with poor outcomes in clear-cell renal cell carcinoma. Expression of HIFα isoforms has been linked to distinct molecular phenotypes of clear-cell renal cell carcinoma. We hypothesized that Chromosome 14 loss could lead to a decrease in HIF1α levels, as its gene (HIF1A) resides in this Chromosome. We analyzed 112 archival clear-cell renal cell carcinoma tumor specimens with 250K SNP microarrays. We also evaluated expression of HIFα isoforms by qPCR and immunohistochemistry in a subset of 30 patients. Loss of Chromosome 14q was associated with high stage (III–IV, P=0.001), high risk for recurrence (P=0.002, RR 2.78 (1.506–5.153)) and with decreased overall survival (P=0.030) in non-metastatic clear-cell renal cell carcinoma. HIF1α mRNA and protein expression was reduced in specimens with loss of 14q (P=0.014) whereas HIF2α was not. Gain of 8q was associated with decreased overall survival (P<0.0001). Our studies confirm an association between 14q loss and clinical outcome in non-metastatic clear-cell renal cell carcinoma patients and that 8q gain is a candidate prognostic marker for decreased overall survival and appears to further decrease survival in patients with 14q loss. We have also identified that differential expression of HIF1α is associated with 14q loss. Further exploration of 8q gain, 14q loss, MYC, HIF1A and EPAS1 (HIF2α) as molecular markers of tumor behavior and prognosis could aid in personalizing medicine for patients with clear-cell renal cell carcinoma.
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Chromosome 14q loss defines a molecular subtype of clear-cell renal cell carcinoma associated with poor prognosis
Modern Pathology, 2011Co-Authors: Federico A Monzon, Leif E Peterson, Nizar M Tannir, Karla Alvarez, Luan D. Truong, Robert J. Amato, Joan Hernandez-mcclain, Anil V. Parwani, Eric JonaschAbstract:Loss of Chromosome 14 has been associated with poor outcomes in clear-cell renal cell carcinoma. Expression of HIFα isoforms has been linked to distinct molecular phenotypes of clear-cell renal cell carcinoma. We hypothesized that Chromosome 14 loss could lead to a decrease in HIF1α levels, as its gene (HIF1A) resides in this Chromosome. We analyzed 112 archival clear-cell renal cell carcinoma tumor specimens with 250K SNP microarrays. We also evaluated expression of HIFα isoforms by qPCR and immunohistochemistry in a subset of 30 patients. Loss of Chromosome 14q was associated with high stage (III–IV, P=0.001), high risk for recurrence (P=0.002, RR 2.78 (1.506–5.153)) and with decreased overall survival (P=0.030) in non-metastatic clear-cell renal cell carcinoma. HIF1α mRNA and protein expression was reduced in specimens with loss of 14q (P=0.014) whereas HIF2α was not. Gain of 8q was associated with decreased overall survival (P
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Chromosome 14q imbalances and pathways associated with resistance to antiangiogenic therapy in clear cell renal cell carcinoma
Journal of Clinical Oncology, 2011Co-Authors: E Jonasch, K Alvarez, Leif E Peterson, Nizar M Tannir, Kanishka Sircar, Pheroze Tamboli, Federico A MonzonAbstract:339 Background: Antiangiogenic agents are used to treat metastatic clear cell renal cell carcinoma (ccRCC). Currently there are no biomarkers of therapeutic efficacy for these agents. Hypoxia inducible factor (HIF) alpha ratios have been linked to phenotypically distinct ccRCC subpopulations. The HIF1 alpha gene is located on Chromosome 14q. In this study, the goal was to determine whether chromosomal imbalances identified with SNP arrays are linked to HIF ratios, and to clinical outcome. Methods: We obtained archival FFPE tumor specimens from 56 patients with mRCC treated with sorafenib or bevacizumab. DNA from the FFPE blocks was analyzed with Affymetrix 250K Nsp SNP microarrays. We identified the presence of genomic imbalances and loss of heterozygosity (LOH) to obtain virtual karyotypes. We then evaluated candidate genes in gain/lost chromosomal regions by qPCR and immunohistochemistry (IHC) in the bevacizumab treated specimens. Results: In the bevacizumab cohort, HIF1-alpha containing14q loss showed ...
Alexandra Durr - One of the best experts on this subject based on the ideXlab platform.
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quality assessment of whole genome mapping data in the refined familial spastic paraplegia interval on Chromosome 14q
Genome Research, 1998Co-Authors: Caroline Paternotte, Alexandra Durr, Doda Rudnicki, Cecile Fizames, Claire Sophie Davoine, Delphine Mavel, Delphine Samson, Catherine Marquette, Delphine Muselet, Nathalie VegaczarnyAbstract:Familial spastic paraplegia (FSP) is a heterogeneous group of degenerative disorders of the central motor system characterized by progressive spasticity of the lower limbs. FSP has been classified (Sutherland 1975) according to the mode of inheritance and whether spasticity occurs in isolation (pure FSP) or with additional symptoms (complicated FSP). In pure FSP, inheritance is most commonly autosomal dominant (AD-FSP) although both pure and complicated FSP may be transmitted as autosomal dominant, autosomal recessive, or X Chromosome-linked traits. Pure AD-FSP is genetically heterogeneous and three AD-FSP-causing loci have been identified to date: SPG3 on Chromosome 14q (Hazan et al. 1993; Gispert et al. 1995), SPG4 on Chromosome 2p (Hazan et al. 1994; Hentati et al. 1994), and SPG6 on Chromosome 15q (Fink et al. 1995). Known AD-FSP loci have been excluded in ∼50% of AD-FSP families (Hereditary Spastic Paraplegia Working Group 1996), providing evidence for the existence of at least a fourth locus. Linkage to Chromosome 2p has been observed in the majority of the AD-FSP pedigrees analyzed so far (Hazan et al. 1994; Dube et al. 1995; Lennon et al. 1995; Hereditary Spastic Paraplegia Working Group 1996), whereas linkage to Chromosome 15q has only been detected in one large North American kindred (Fink et al. 1995). Linkage to Chromosome 14q has been reported in five AD-FSP pedigrees, including one French (Hazan et al. 1993), one German (Gispert et al. 1995), one Tibetan (Huang et al. 1997), and two North American (Hentati et al. 1994; Lennon et al. 1995) families. Recombinant analysis and linkage data first placed SPG3 within a 15-cM interval between markers D14S266 and D14S66 (Hazan et al. 1993). The SPG3 candidate region was then reduced to a 7-cM interval flanked by loci D14S288 and D14S281 (Gispert et al. 1995). The distance between D14S288 and D14S281 was then re-evaluated at 9 cM in the last version of the Genethon map (Dib et al. 1996). Here, we report linkage to Chromosome 14q in an additional French family and present the refined genetic map of the SPG3 candidate interval using microsatellite markers from a published set (Dib et al. 1996). Subsequent studies of recombination events in two pedigrees from France and one from Germany allowed us to narrow the SPG3 region to 5 cM between markers D14S259 and D14S1018. As a first step toward the isolation of one of the genes responsible for AD-FSP, we constructed an ∼5-Mb YAC contig from D14S301 to D14S991 consisting of 32 clones. To evaluate the whole genome mapping data in this particular region of 14q21, our physical map was compared with the Whitehead/MIT contig WC14.1 (Hudson et al. 1995), which revealed some discrepancies in both STS order and YAC/STS content. To establish a transcript map, 104 ESTs that had been localized within or near the SPG3 interval (Schuler et al. 1996) with two radiation hybrid (RH) panels, Genebridge 4 (Gyapay et al. 1996) and G3 (Stewart et al. 1997), were tested by PCR on the 32 YAC clones of the contig: 56 ESTs including 10 known genes were mapped to the YAC contig between D14S301 and D14S991; 24 of them belong to the restricted SPG3 interval flanked by loci D14S259 and D14S1018. To compare the YAC physical map of the critical region with an RH map with a higher level of resolution, the 90 STSs positioned on the SPG3 YAC contig were tested on a third RH panel, the TNG panel (Lunetta et al. 1996) which could be used to order markers at 50-kb resolution. In this paper we integrate all of the RH and YAC data into an accurate high-resolution physical and transcript map of the SPG3 interval that represents a powerful tool for identification of the gene responsible for this form of FSP.
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The gene for Machado–Joseph disease maps to the same 3-cM interval as the spinal cerebellar ataxia 3 gene on Chromosome 14q
Neurobiology of Disease, 1994Co-Authors: Giovanni Stevanin, Alexandra Durr, Jean Weissenbach, P S Sousa, Geraldine Cancel, O Dubourg, Garth A Nicholson, E Jardim, Y Agid, E CassaAbstract:Abstract Machado–Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder in families of Portuguese–Azorean ancestry. The gene responsible for MJD has been assigned to a 29-cM interval on Chromosome 14q. A large Brazilian family with MJD was genotyped with six new microsatellite markers spanning 19 cM on Chromosome 14q. Linkage analysis and haplotype reconstruction reduced the MJD candidate region to a 3-cM interval between markers D14S280 and D14S81, permitting positional cloning. This interval also contains the spinal cerebellar ataxia 3 ( SCA3 ) gene, responsible for a genetic subtype of the type I autosomal dominant cerebellar ataxias, clinically related to MJD. This result supports the hypothesis that abnormalities in the same gene may be responsible for both disorders. The minor clinical differences between the two diseases may result from allelic heterogeneity.
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the gene for machado joseph disease maps to the same 3 cm interval as the spinal cerebellar ataxia 3 gene on Chromosome 14q
Neurobiology of Disease, 1994Co-Authors: Giovanni Stevanin, Alexandra Durr, Jean Weissenbach, P S Sousa, Geraldine Cancel, O Dubourg, Garth A Nicholson, E Jardim, Y Agid, E CassaAbstract:Abstract Machado–Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder in families of Portuguese–Azorean ancestry. The gene responsible for MJD has been assigned to a 29-cM interval on Chromosome 14q. A large Brazilian family with MJD was genotyped with six new microsatellite markers spanning 19 cM on Chromosome 14q. Linkage analysis and haplotype reconstruction reduced the MJD candidate region to a 3-cM interval between markers D14S280 and D14S81, permitting positional cloning. This interval also contains the spinal cerebellar ataxia 3 ( SCA3 ) gene, responsible for a genetic subtype of the type I autosomal dominant cerebellar ataxias, clinically related to MJD. This result supports the hypothesis that abnormalities in the same gene may be responsible for both disorders. The minor clinical differences between the two diseases may result from allelic heterogeneity.
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linkage of a new locus for autosomal dominant familial spastic paraplegia to Chromosome 2p
Human Molecular Genetics, 1994Co-Authors: Alexandra Durr, Jamile Hazan, R.p.m. Bruyn, Clalresophie Rime, Judith Melkl, Judith C T Van Deutekom, B. Fontaine, C Lamy, O LyoncaenAbstract:: Autosomal dominant familial spastic paraplegia (AD-FSP) is a genetically heterogeneous neurodegenerative disorder characterized by a spasticity of the lower limbs. A locus causing AD-FSP (FSP1) has been previously mapped to Chromosome 14q. We now report linkage of a second AD-FSP locus (FSP2) to Chromosome 2p21-p24 in five of seven French families and one large Dutch pedigree. The analysis of recombination events and multipoint linkage place FSP2 within a 4 cM interval flanked by loci D2S400 and D2S367.
Davut Pehlivan - One of the best experts on this subject based on the ideXlab platform.
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Loss of heterozygosity at Chromosome 14q is associated with poor prognosis in head and neck squamous cell carcinomas
Journal of Cancer Research and Clinical Oncology, 2008Co-Authors: Davut Pehlivan, Esra Gunduz, Mehmet Gunduz, Hitoshi Nagatsuka, Levent Bekir Beder, Beyhan Cengiz, Rosario Santos Rivera, Kunihiro Fukushima, Sukru Palanduz, Sukru OzturkAbstract:Purpose and methods Loss of heterozygosity (LOH) in a chromosomal location indicates the presence of an inactivated tumor suppressor gene (TSG). Inactivation of TSG has a functional role in the tumorigenesis of head and neck squamous cell carcinoma (HNSCC). Based on the recent evidences of a putative TSG on Chromosome 14, we examined LOH on Chromosome 14q using eight polymorphic microsatellite markers in 50 cases of HNSCCs. Results Three regions were detected to have a high LOH rate which included 14q21.2-22.3 (42.5%), 14q31 (55%), and 14q32.1 (37%). The correlation between LOH and clinicopathological findings was investigated through statistical analyses. A strong correlation was observed between the highest LOH marker and the overall and disease-free survival. Conclusions The results suggest that the distal part of Chromosome 14 may host a TSG that may lead to the development and/or progression of HNSCCs. Several genes such as CHES1, BMP4, SAV, and PNN have arisen as candidate tumor suppressors in the region.
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loss of heterozygosity at Chromosome 14q is associated with poor prognosis in head and neck squamous cell carcinomas
Journal of Cancer Research and Clinical Oncology, 2008Co-Authors: Davut Pehlivan, Esra Gunduz, Mehmet Gunduz, Hitoshi Nagatsuka, Levent Bekir Beder, Beyhan Cengiz, Rosario Santos Rivera, Kunihiro FukushimaAbstract:Purpose and methods Loss of heterozygosity (LOH) in a chromosomal location indicates the presence of an inactivated tumor suppressor gene (TSG). Inactivation of TSG has a functional role in the tumorigenesis of head and neck squamous cell carcinoma (HNSCC). Based on the recent evidences of a putative TSG on Chromosome 14, we examined LOH on Chromosome 14q using eight polymorphic microsatellite markers in 50 cases of HNSCCs.
James A Grunkemeyer - One of the best experts on this subject based on the ideXlab platform.
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linkage of usher syndrome type i gene ush1b to the long arm of Chromosome 11
Genomics, 1992Co-Authors: William J. Kimberling, Michael D Weston, Claes Möller, S Davenport, I A Priluck, Peter Beighton, Jacquie Greenberg, J B Kenyon, William Reardon, James A GrunkemeyerAbstract:Usher syndrome is the most commonly recognized cause of combined visual and hearing loss in technologically developed countries. There are several different types and all are inherited in an autosomal recessive manner. There may be as many as five different genes responsible for at least two closely related phenotypes. The nature of the gene defects is unknown, and positional cloning strategies are being employed to identify the genes. This is a report of the localization of one gene for Usher syndrome type I to Chromosome 11q, probably distal to marker D11S527. Another USH1 gene had been previously localized to Chromosome 14q, and this second localization establishes the existence of a new and independent locus for Usher syndrome.