title: Cloning and characterization of three novel genes, ALS2CR1, ALS2CR2, and ALS2CR3, in the juvenile amyotrophic lateral sclerosis (ALS2) critical region at chromosome 2q33-q34: candidate genes for ALS2.
abstract: Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that manifests as selective upper and lower motor neuron degeneration. The autosomal recessive form of juvenile amyotrophic lateral sclerosis (ALS2) has previously been mapped to the 1.7-cM interval flanked by D2S116 and D2S2237 on human chromosome 2q33-q34. We identified three novel full-length transcripts encoded by three distinct genes (HGMW-approved symbols ALS2CR1, ALS2CR2, and ALS2CR3) within the ALS2 critical region. The intron-exon organizations of these genes as well as those of CFLAR, CASP10, and CASP8, which were previously mapped to this region, were defined. These genes were evaluated for mutations in ALS2 patients, and no disease-associated sequence alterations in either exons or intron-exon boundaries were observed. Sequence analysis of overlapping RT-PCR products covering the whole coding sequence for each transcript revealed no aberrant mRNA sequences. These data strongly indicate that ALS2CR1, ALS2CR2, ALS2CR3, CFLAR, CASP10, and CASP8 are not causative genes for ALS2.
authors.affiliation: NeuroGenes, International Cooperative Research Project, Japan Science and Technology Corporation, Isehara, 259-1193, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hadano
authors.forename: Y
authors.initials: Y
authors.lastname: Yanagisawa
authors.forename: J
authors.initials: J
authors.lastname: Skaug
authors.forename: K
authors.initials: K
authors.lastname: Fichter
authors.forename: J
authors.initials: J
authors.lastname: Nasir
authors.forename: D
authors.initials: D
authors.lastname: Martindale
authors.forename: B F
authors.initials: BF
authors.lastname: Koop
authors.forename: S W
authors.initials: SW
authors.lastname: Scherer
authors.forename: D W
authors.initials: DW
authors.lastname: Nicholson
authors.forename: G A
authors.initials: GA
authors.lastname: Rouleau
authors.forename: J
authors.initials: J
authors.lastname: Ikeda
authors.forename: M R
authors.initials: MR
authors.lastname: Hayden
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D002352:Carrier Proteins; D053455:Caspase 10; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D003001:Cloning, Molecular; D056970:Co-Repressor Proteins; D016384:Consensus Sequence; D004252:DNA Mutational Analysis; D015723:Gene Library; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics; D020161:Physical Chromosome Mapping; D011506:Proteins; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D002352:Carrier Proteins; D056970:Co-Repressor Proteins; D047908:Intracellular Signaling Peptides and Proteins; C419199:NIF3L1 protein, human; D009419:Nerve Tissue Proteins; D011506:Proteins; D012333:RNA, Messenger; C429291:STRADB protein, human; C465341:TRAK2 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053455:Caspase 10; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; C506438:CASP10 protein, human