ArticleGenome medicine2019
Distinct patterns of complex rearrangements and a mutational signature of microhomeology are frequently observed in PLP1 copy number gain structural variants.
Article in Genome medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- De Novo Complex Genomic Rearrangement Spanning 2q31.1 in a Proband With Congenital Malformations: Genotype-Phenotype Correlation and Development of a CGR Detection Pipeline.American journal of medical genetics. Part A · 2026Article
- Developmental trajectory of individuals with Pelizaeus-Merzbacher Disease (PMD).Molecular genetics and metabolism · 2026Article
- Widespread distribution of Alu/Alu-mediated genomic rearrangement predisposing to a broad range of Mendelian disease and cancer in human populations.Genome medicine · 2026Article
- Palindrome-mediated 16p13.3 triplications cause a recognizable neurodegenerative disorder with ataxia.American journal of human genetics · 2026Article
- Complex de novo structural variants are an underestimated cause of rare disorders.Nature communications · 2025Article
- Combining long-read DNA and RNA sequencing to enhance molecular understanding of structural variations leading to copy gains.Computational and structural biotechnology journal · 2025Article
- Diet and Nutrients in Rare Neurological Disorders: Biological, Biochemical, and Pathophysiological Evidence.Nutrients · 2024Review
- Inverted triplications formed by iterative template switches generate structural variant diversity at genomic disorder loci.Cell genomics · 2024Article
- Complete F9 Gene Deletion, Duplication, and Triplication Rearrangements: Implications for Factor IX Expression and Clinical Phenotypes.Thrombosis and haemostasis · 2024Article
- Identification and preliminary analysis of hub genes associated with bladder cancer progression by comprehensive bioinformatics analysis.Scientific reports · 2024Article
- Complex rearrangement in TBC1D4 in an individual with diabetes due to severe insulin resistance syndrome.European journal of human genetics : EJHG · 2024Article
- Recent gene selection and drug resistance underscore clinical adaptation across Candida species.Nature microbiology · 2024Article
- SNV/indel hypermutator phenotype in biallelic RAD51C variant: Fanconi anemia.Human genetics · 2023Article
- Identification and characterisation of de novo germline structural variants in two commercial pig lines using trio-based whole genome sequencing.BMC genomics · 2023Article
- SNV/indel hypermutator phenotype in biallelic RAD51C variant - Fanconi anemia.Research square · 2023Article
- Article
- TCEAL1 loss-of-function results in an X-linked dominant neurodevelopmental syndrome and drives the neurological disease trait in Xq22.2 deletions.American journal of human genetics · 2022Article
- Complex genomic rearrangements: an underestimated cause of rare diseases.Trends in genetics : TIG · 2022Review
- Xq27.1 palindrome mediated interchromosomal insertion likely causes familial congenital bilateral laryngeal abductor paralysis (Plott syndrome).Journal of human genetics · 2022Article
- Biology in balance: human diploid genome integrity, gene dosage, and genomic medicine.Trends in genetics : TIG · 2022Review
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12 authors.
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Abstract
backgroundWe investigated the features of the genomic rearrangements in a cohort of 50 male individuals with proteolipid protein 1 (PLP1) copy number gain events who were ascertained with Pelizaeus-Merzbacher disease (PMD; MIM: 312080). We then compared our new data to previous structural variant mutagenesis studies involving the Xq22 region of the human genome. The aggregate data from 159 sequenced join-points (discontinuous sequences in the reference genome that are joined during the rearrangement process) were studied. Analysis of these data from 150 individuals enabled the spectrum and relative distribution of the underlying genomic mutational signatures to be delineated.
methodsGenomic rearrangements in PMD individuals with PLP1 copy number gain events were investigated by high-density customized array or clinical chromosomal microarray analysis and breakpoint junction sequence analysis.
resultsHigh-density customized array showed that the majority of cases (33/50; ~ 66%) present with single duplications, although complex genomic rearrangements (CGRs) are also frequent (17/50; ~ 34%). Breakpoint mapping to nucleotide resolution revealed further previously unknown structural and sequence complexities, even in single duplications. Meta-analysis of all studied rearrangements that occur at the PLP1 locus showed that single duplications were found in ~ 54% of individuals and that, among all CGR cases, triplication flanked by duplications is the most frequent CGR array CGH pattern observed. Importantly, in ~ 32% of join-points, there is evidence for a mutational signature of microhomeology (highly similar yet imperfect sequence matches).
conclusionsThese data reveal a high frequency of CGRs at the PLP1 locus and support the assertion that replication-based mechanisms are prominent contributors to the formation of CGRs at Xq22. We propose that microhomeology can facilitate template switching, by stabilizing strand annealing of the primer using W-C base complementarity, and is a mutational signature for replicative repair.
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