title: Genome-wide copy number variation in sporadic amyotrophic lateral sclerosis in the Turkish population: deletion of EPHA3 is a possible protective factor.
abstract: The genome-wide presence of copy number variations (CNVs), which was shown to affect the expression and function of genes, has been recently suggested to confer risk for various human disorders, including Amyotrophic Lateral Sclerosis (ALS). We have performed a genome-wide CNV analysis using PennCNV tool and 733K GWAS data of 117 Turkish ALS patients and 109 matched healthy controls. Case-control association analyses have implicated the presence of both common (>5%) and rare (<5%) CNVs in the Turkish population. In the framework of this study, we identified several common and rare loci that may have an impact on ALS pathogenesis. None of the CNVs associated has been implicated in ALS before, but some have been reported in different types of cancers and autism. The most significant associations were shown for 41 kb and 15 kb intergenic heterozygous deletions (Chr11: 50,545,009-50,586,426 and Chr19: 20,860,930-20,875,787) both contributing to increased risk for ALS. CNVs in coding regions of the MAP4K3, HLA-B, EPHA3 and DPYD genes were detected however, after validation by Log R Ratio (LRR) values and TaqMan CNV genotyping, only EPHA3 deletion remained as a potential protective factor for ALS (p = 0.0065024). Based on the knowledge that EPHA4 has been previously shown to rescue SOD1 transgenic mice from ALS phenotype and prolongs survival, EPHA3 may be a promising candidate for therepuetic interventions.
authors.affiliation: Suna and İnan Kıraç Foundation Neurodegeneration Research Laboratory, Molecular Biology and Genetics Department, Bogazici University, Istanbul, Turkey.
authors.forename: Özgün
authors.initials: Ö
authors.lastname: Uyan
authors.forename: Özgür
authors.initials: Ö
authors.lastname: Ömür
authors.forename: Zeynep Sena
authors.initials: ZS
authors.lastname: Ağım
authors.forename: Aslıhan
authors.initials: A
authors.lastname: Özoğuz
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Yeşim
authors.initials: Y
authors.lastname: Parman
authors.forename: Feza
authors.initials: F
authors.lastname: Deymeer
authors.forename: Piraye
authors.initials: P
authors.lastname: Oflazer
authors.forename: Filiz
authors.initials: F
authors.lastname: Koç
authors.forename: Ersin
authors.initials: E
authors.lastname: Tan
authors.forename: Hilmi
authors.initials: H
authors.lastname: Özçelik
authors.forename: A Nazlı
authors.initials: AN
authors.lastname: Başak
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D016022:Case-Control Studies; D017353:Gene Deletion; D018628:Gene Dosage; D015894:Genome, Human; D006801:Humans; D016133:Polymerase Chain Reaction; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D036121:Receptor, EphA3; D014421:Turkey
chemical_list: C491718:EPHA3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D036121:Receptor, EphA3