Fine Localization of the Torsion Dystonia Gene (<i>DYT1</i>) on Human Chromosome 9q34: YAC Map and Linkage Disequilibrium

Ozelius, Laurie J.; Hewett, Jeffrey; Kramer, Patricia L.; Bressman, Susan; Shalish, Christo; Leon, Deborah de; Rutter, M.; Risch, Neil; Brin, Mitchell F.; Markova, E D; Limborska, Svetlana A.; Ivanova-Smolenskaya, I. A.; McCormick, Mary Kay; Fahn, Stanley; Buckler, Alan; Gusella, James F.; Breakefield, Xandra O.

doi:10.1101/gr.7.5.483

Cited by 60 publications

(39 citation statements)

References 35 publications

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“…Two tumors (84 and 143) showed LOH at D9S113 with retention of adjoining markers. Within this region several genes have been mapped, including the ABO gene-encoded glycosyltransferase (Meldgaard et al, 1995), the tuberous sclerosis gene (TSC1), the nail-patella syndrome 1 (NPS1) (Povey et al, 1994), the torsion dystonia gene (DYT1) (Ozelius et al, 1997), the collagen type V a1 chain (COL5A1) (Northrup et al, 1994) and the hereditary hemorrhagic telangiectasia gene (HHT) . The TSC1 (Hornigold et al, 1997;van Slegtenhorst et al, 1997) and ABO loci are located distal to the ASS locus and should be excluded on the basis of tumor 63 which had only the ASS locus deleted (Figure 4c, tumor 63).…”

Section: Discussionmentioning

confidence: 99%

Four tumor suppressor loci on chromosome 9q in bladder cancer: evidence for two novel candidate regions at 9q22.3 and 9q31

et al. 1999

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The most common genetic alteration identi®ed in transitional cell carcinoma (TCC) of the bladder is loss of heterozygosity (LOH) on chromosome 9. However, localization of tumor suppressor genes on 9q has been hampered by the low frequency of subchromosomal deletions. We have analysed 139 primary, initial low stage TCC of the bladder using a panel of 28 microsatellite markers spanning chromosome 9 at an average distance of 5 Mb, following a primer-extension preampli®cation (PEP) technique. Sixty-seven (48%) tumors showed LOH at one or more loci and partial deletions were detected in 62 (45%) tumors; apparent monosomy 9 was detected in only ®ve (4%) tumors. Deletions were more frequent on 9q (44%) than on 9p (23%), the latter being mostly associated with 9q deletion, suggesting that alteration of genes on 9q may be an early event associated with super®cial papillary tumors. Combined data from the cases with partial 9q deletions displayed four candidate regions for tumor suppressor loci, based on the frequency of deletion observed and tumors with unique deletions at these sites. In two tumors, the unique partial deletion comprised D9S12 at 9q22.3, a region encompassing loci for the Gorlin syndrome and multiple self-healing squamous epithelioma gene. In two other tumors, the single LOH was identi®ed at the D9S172 locus at 9q31-32 where the dysautonia and Fukuyama-type congenital muscular dystrophy genes have been located. One tumor showed unique LOH at the GSN locus at 9q33, a region frequently deleted in other sporadic tumors while the fourth region of deletion was observed at 9q34 between ASS and ABL-1, in two tumors. This region is frequently deleted in tumors and encompasses the locus for the hereditary hemorrhagic telangiectasia gene. These ®ndings suggest four target regions on 9q within which suppressor genes for TCC may reside.

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Section: Discussionmentioning

confidence: 99%

Four tumor suppressor loci on chromosome 9q in bladder cancer: evidence for two novel candidate regions at 9q22.3 and 9q31

et al. 1999

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“…Dystonia can be classified by the presence or absence of associated clinical manifestations, differentiating Bisolated dystonia^from Bcombined dystonia^, where dystonia appears as a component of other disorders, such as PD. In adults, focal forms of dystonia are common, whereas in children and young adults, generalized inherited forms of dystonia are more common, such as idiopathic torsion dystonia [DYT1; 181].…”

Section: Dystoniamentioning

confidence: 99%

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

2016

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Deep brain stimulation (DBS) is highly effective for both hypo-and hyperkinetic movement disorders of basal ganglia origin. The clinical use of DBS is, in part, empiric, based on the experience with prior surgical ablative therapies for these disorders, and, in part, driven by scientific discoveries made decades ago. In this review, we consider anatomical and functional concepts of the basal ganglia relevant to our understanding of DBS mechanisms, as well as our current understanding of the pathophysiology of two of the most commonly DBS-treated conditions, Parkinson's disease and dystonia. Finally, we discuss the proposed mechanism(s) of action of DBS in restoring function in patients with movement disorders. The signs and symptoms of the various disorders appear to result from signature disordered activity in the basal ganglia output, which disrupts the activity in thalamocortical and brainstem networks. The available evidence suggests that the effects of DBS are strongly dependent on targeting sensorimotor portions of specific nodes of the basal gangliathalamocortical motor circuit, that is, the subthalamic nucleus and the internal segment of the globus pallidus. There is little evidence to suggest that DBS in patients with movement disorders restores normal basal ganglia functions (e.g., their role in movement or reinforcement learning). Instead, it appears that high-frequency DBS replaces the abnormal basal ganglia output with a more tolerable pattern, which helps to restore the functionality of downstream networks.

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“…The cause of DYT1 in most patients is the result of a glutamic acid deletion in the torsinA protein [135]. TorsinA is an ATPase associated with diverse cellular activities [136], whose mutant form (TorsinA(ΔE)) is thought to have a dominant negative effect [137,138].…”

Section: Dystoniamentioning

confidence: 99%

Recent Advances in RNA Interference Therapeutics for CNS Diseases

2013

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Over the last decade, RNA interference technology has shown therapeutic promise in rodent models of dominantly inherited brain diseases, including those caused by polyglutamine repeat expansions in the coding region of the affected gene. For some of these diseases, proof-of concept studies in model organisms have transitioned to safety testing in larger animal models, such as the nonhuman primate. Here, we review recent progress on RNA interference-based therapies in various model systems. We also highlight outstanding questions or concerns that have emerged as a result of an improved (and ever advancing) understanding of the technologies employed.

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Fine Localization of the Torsion Dystonia Gene (DYT1) on Human Chromosome 9q34: YAC Map and Linkage Disequilibrium

Cited by 60 publications

References 35 publications

Four tumor suppressor loci on chromosome 9q in bladder cancer: evidence for two novel candidate regions at 9q22.3 and 9q31

Four tumor suppressor loci on chromosome 9q in bladder cancer: evidence for two novel candidate regions at 9q22.3 and 9q31

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

Recent Advances in RNA Interference Therapeutics for CNS Diseases

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