title: A survey of trinucleotide/tandem repeat-containing transcripts (TNRTs) isolated from human spinal cord to identify genes containing unstable DNA regions as candidates for disorders of motor function.
abstract: Expansion of unstable DNA regions containing trinucleotide/tandem repeats (TNRs) represents a common genetic mutation in hereditary forms of neurological disorders. The spectrum of neurological diseases linked to TNR expansions has recently broadened to include conditions with both dominant and recessive inheritance and those with or without clinical anticipation. In view of the frequent involvement of the spinal cord in neurodegenerative disorders, we have analysed this key tissue to identify pathological TNRs. We have used two approaches to isolate a wide range of trinucleotide/tandem repeat-containing transcripts (TNRTs) from human spinal cord, firstly a polymerase chain reaction (PCR)-based method and secondly by screening a spinal cord cDNA library immobilised on a membrane. Overall, 97 TNRTs belonging to a number of key protein families, the most highly represented being transcription factors, intracellular signalling molecules and cytoskeletal proteins, have been isolated most of which have not previously been considered as potential disease-causing genes. The commonest repeat motifs found in our study were CAG (37%) and CCG (24%). Known genes involved in DNA repeat expansion-related neurological disorders (e.g., AAD10, Ataxin-3, Huntingtin) were detected which validated our methods. We have characterised homogeneous TNRs among the detected gene candidates in a search for potential pathological repeat expansions. The potential role of the gene candidates identified is discussed in terms of their contribution to neurodegenerative processes.
authors.affiliation: Department of Neuromuscular Diseases, Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Malaspina
authors.forename: N
authors.initials: N
authors.lastname: Kaushik
authors.forename: J
authors.initials: J
authors.lastname: de Belleroche
mesh_terms: D015723:Gene Library; D005820:Genetic Testing; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000592:standards; D010455:Peptides / Q000235:genetics; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D013116:Spinal Cord / Q000502:physiology*; D018911:Trinucleotide Repeats
chemical_list: D009419:Nerve Tissue Proteins; D010455:Peptides; C097188:polyglutamine