Erratum: Sequence analysis of 17 NRXN1 deletions

Abstract

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 analyze 17 carriers of nonrecurrent deletions in the NRXN1 gene, which have been associated with neurodevelopmental disorders, for example, schizophrenia, autism, and epilepsy. Methods: Seventeen nonrecurrent NRXN1 deletions identified by GWA studies were sequenced to map the breakpoints of each. We then performed a sequence analysis of each breakpoint region for the presence of minus self-chains, novel sequence motifs, sequence motifs previously associated with genomic rearrangements, repetitive DNA elements and the flanking AT nucleotide content. 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. In addition, we found small insertions and duplications together with short stretches of microhomology within the breakpoint regions. 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 the NRXN1 deletions may lead to increased instability leading to an increased susceptibility to single stranded structures. This is potentially repaired by the NHEJ mechanism or may lead to replication errors. © 2014.