title: Identification of candidate genes for sporadic amyotrophic lateral sclerosis by array comparative genomic hybridization.
abstract: Amyotrophic lateral sclerosis (ALS) is a devastating disorder of the central nervous system that leads to progressive loss of upper and lower motor neurons. Most cases are sporadic and of unknown aetiology. In this study, we screened 72 patients with sporadic ALS for the presence of DNA copy number variations, in order to identify novel candidate disease genes. We have used sub-megabase resolution BAC array comparative genomic hybridization to detect genomic imbalances in our ALS patient cohort. Aberrations with potential relevance for disease aetiology were verified by oligo array CGH. In 72 patients with sporadic ALS, we identified a total of six duplications and five deletions that scored above our threshold. Nine of these 11 variations were smaller than 1Mb, and five were observed exclusively in ALS patients. In conclusion, non-polymorphic sub-microscopic duplications and deletions observable by array CGH are frequent in patients with sporadic ALS. Analysis of such aberrations serves as a starting point in deciphering the aetiology of this complex disease, given that affected genes can be considered candidates for influencing disease susceptibility.
authors.affiliation: Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Shoichet
authors.forename: Stefan
authors.initials: S
authors.lastname: Waibel
authors.forename: Sonja
authors.initials: S
authors.lastname: Endruhn
authors.forename: Anne D
authors.initials: AD
authors.lastname: Sperfeld
authors.forename: Brita
authors.initials: B
authors.lastname: Vorwerk
authors.forename: Ines
authors.initials: I
authors.lastname: Müller
authors.forename: Fikret
authors.initials: F
authors.lastname: Erdogan
authors.forename: Albert C
authors.initials: AC
authors.lastname: Ludolph
authors.forename: Hans-Hilger
authors.initials: HH
authors.lastname: Ropers
authors.forename: Reinhard
authors.initials: R
authors.lastname: Ullmann
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000503:physiopathology; D055028:Comparative Genomic Hybridization; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*