ArticleAmerican journal of human genetics2013
Molecular analysis of a deletion hotspot in the NRXN1 region reveals the involvement of short inverted repeats in deletion CNVs.
Article in American journal of human genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- The Impact of Environmental and Endogenous Damage on Somatic Mutation Load in Human Skin Fibroblasts.PLoS genetics · 2016Trial
- Correlation of mutated gene and signalling pathways in ASD.IBRO neuroscience reports · 2023Review
- Evaluation of Individuals with Non-Syndromic Global Developmental Delay and Intellectual Disability.Children (Basel, Switzerland) · 2023Review
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- WWOX Loss of Function in Neurodevelopmental and Neurodegenerative Disorders.International journal of molecular sciences · 2020Review
- Xq22 deletions and correlation with distinct neurological disease traits in females: Further evidence for a contiguous gene syndrome.Human mutation · 2020Article
- A key 'foxy' aroma gene is regulated by homology-induced promoter indels in the iconic juice grape 'Concord'.Horticulture research · 2020Article
- Modulation of DNA structure formation using small molecules.Biochimica et biophysica acta. Molecular cell research · 2019Review
- Breakpoint junction features of seven DMD deletion mutations.Human genome variation · 2019Article
- A complex intragenic rearrangement of ERCC8 in Chinese siblings with Cockayne syndrome.Scientific reports · 2017Article
- Using hiPSCs to model neuropsychiatric copy number variations (CNVs) has potential to reveal underlying disease mechanisms.Brain research · 2017Review
- Review
- Detection of cis- and trans-acting Factors in DNA Structure-Induced Genetic Instability Using In silico and Cellular Approaches.Frontiers in genetics · 2016Article
- Genetics of Autism Spectrum Disorder: Current Status and Possible Clinical Applications.Experimental neurobiology · 2015Review
- Decoding NF1 Intragenic Copy-Number Variations.American journal of human genetics · 2015Article
- Mutations in NDUFB11, encoding a complex I component of the mitochondrial respiratory chain, cause microphthalmia with linear skin defects syndrome.American journal of human genetics · 2015Article
- Genome architecture and its roles in human copy number variation.Genomics & informatics · 2014Review
- Identification of candidate single-nucleotide polymorphisms in NRXN1 related to antipsychotic treatment response in patients with schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2014Article
- Impact of alternative DNA structures on DNA damage, DNA repair, and genetic instability.DNA repair · 2014Review
- SVA retrotransposon insertion-associated deletion represents a novel mutational mechanism underlying large genomic copy number changes with non-recurrent breakpoints.Genome biology · 2014Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
NRXN1 microdeletions occur at a relatively high frequency and confer increased risk for neurodevelopmental and neurobehavioral abnormalities. The mechanism that makes NRXN1 a deletion hotspot is unknown. Here, we identified deletions of the NRXN1 region in affected cohorts, confirming a strong association with the autism spectrum and other neurodevelopmental disorders. Interestingly, deletions in both affected and control individuals were clustered in the 5' portion of NRXN1 and its immediate upstream region. To explore the mechanism of deletion, we mapped and analyzed the breakpoints of 32 deletions. At the deletion breakpoints, frequent microhomology (68.8%, 2-19 bp) suggested predominant mechanisms of DNA replication error and/or microhomology-mediated end-joining. Long terminal repeat (LTR) elements, unique non-B-DNA structures, and MEME-defined sequence motifs were significantly enriched, but Alu and LINE sequences were not. Importantly, small-size inverted repeats (minus self chains, minus sequence motifs, and partial complementary sequences) were significantly overrepresented in the vicinity of NRXN1 region deletion breakpoints, suggesting that, although they are not interrupted by the deletion process, such inverted repeats can predispose a region to genomic instability by mediating single-strand DNA looping via the annealing of partially reverse complementary strands and the promoting of DNA replication fork stalling and DNA replication error. Our observations highlight the potential importance of inverted repeats of variable sizes in generating a rearrangement hotspot in which individual breakpoints are not recurrent. Mechanisms that involve short inverted repeats in initiating deletion may also apply to other deletion hotspots in the human genome.
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Registered trials
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