title: Sequence analysis of 17 NRXN1 deletions.
abstract: BACKGROUND
  Genome instability plays fundamental roles in human evolution and phenotypic variation within our population. This instability leads to genomic rearrangements that are involved in a wide variety of human disorders, including congenital and neurodevelopmental disorders, and cancers. Insight into the molecular mechanisms governing such genomic rearrangements may increase our understanding of disease pathology and evolutionary processes. Here we analyse 17 carriers of non-recurrent deletions in the NRXN1 gene, which have been associated with neurodevelopmental disorders, e.g. schizophrenia, autism and epilepsies.
  
  
  METHODS
  17 non-recurrent NRXN1 deletions identified by GWA were sequenced to map the breakpoints of each. Meme … etc. was used to identify shared patterns between the deletions and compare these were previously studies on non-recurrent deletions.
  
  
  RESULTS
  We discovered two novel sequence motifs shared between all 17 NRXN1 deletions and a significantly higher AT nucleotide content at the breakpoints, compared to the overall nucleotide content on chromosome 2. We found different alteration of sequence at the breakpoint; small insertions and duplications giving rise to short microhomology sequences.
  
  
  CONCLUSIONS
  No single mechanism seems to be implicated in the deletion events, but the results suggest that NHEJ, FoSTeS or MMBIR is implicated. The two novel sequence motifs together with a high AT content in all in NRXN1 deletions may lead to increased instability leading to a increase susceptibility to a single stranded structures. This favours potentially repaired by NHEJ mechanism of double strand breaks or may leading to replication errors. © 2013 Wiley Periodicals, Inc.
authors: Research Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark.
authors: Louise Kristine
authors: LK
authors: Enggaard Hoeffding
authors: Thomas
authors: T
authors: Hansen
authors: Andrés
authors: A
authors: Ingason
authors: Linh
authors: L
authors: Doung
authors: Johan H
authors: JH
authors: Thygesen
authors: Rikke S
authors: RS
authors: Møller
authors: Niels
authors: N
authors: Tommerup
authors: George
authors: G
authors: Kirov
authors: Dan
authors: D
authors: Rujescu
authors: Lars A
authors: LA
authors: Larsen
authors: Thomas
authors: T
authors: Werge
mesh_terms: D001321:Autistic Disorder / Q000235:genetics*; D001482:Base Composition / Q000235:genetics; D001483:Base Sequence; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics; D059766:DNA End-Joining Repair / Q000235:genetics; D004827:Epilepsy / Q000235:genetics*; D017353:Gene Deletion; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D042822:Genomic Instability; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019006:Neural Cell Adhesion Molecules; D012559:Schizophrenia / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; C539628:NRXN1 protein, human; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules
keywords: breakpoints; deletion; neurexin 1