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https://www.arca.fiocruz.br/handle/icict/12438
ABSENCE OF HETEROZYGOSITY DUE TO TEMPLATE SWITCHING DURING REPLICATIVE REARRANGEMENTS.
Models, Genetic
Polymorphism, Single Nucleotide/genetics
Sequence Analysis, DNA
Author
Affilliation
Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA/Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil.
Radboud University Nijmegen Medical Centre. Radboud University Medical Center Institute for Molecular Life Sciences. Department of Human Genetics. Nijmegen, the Netherlands.
Wellcome Trust Sanger Institute. Cambridge, UK.
Wellcome Trust Sanger Institute. Cambridge, UK.
Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA
Maastricht University Medical Center. Department of Clinical Genetics. Maastricht, the Netherlands.
Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA
Sheffield Children's NHS Foundation Trust. Sheffield Genetics Service. Sheffield, UK.
Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA
Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA/Baylor College of Medicine. Department of Pediatrics. Houston, TX, USA/Texas Children's Hospital. Houston, TX, USA.
Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA
Wellcome Trust Sanger Institute. Cambridge, UK.
Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA
Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA
Radboud University Nijmegen Medical Centre.Radboud University Medical Center Institute for Molecular Life Sciences. Department of Human Genetics. Nijmegen, the Netherlands/ Maastricht University Medical Center. Department of Clinical Genetics. Maastricht, the Netherlands.
Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA/Baylor College of Medicine. Department of Pediatrics. Houston, TX, USA/ Texas Children's Hospital Houston, TX, USA/Baylor College of Medicine. Human Genome Sequencing Center. Houston, TX, USA.
Radboud University Nijmegen Medical Centre. Radboud University Medical Center Institute for Molecular Life Sciences. Department of Human Genetics. Nijmegen, the Netherlands.
Wellcome Trust Sanger Institute. Cambridge, UK.
Wellcome Trust Sanger Institute. Cambridge, UK.
Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA
Maastricht University Medical Center. Department of Clinical Genetics. Maastricht, the Netherlands.
Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA
Sheffield Children's NHS Foundation Trust. Sheffield Genetics Service. Sheffield, UK.
Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA
Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA/Baylor College of Medicine. Department of Pediatrics. Houston, TX, USA/Texas Children's Hospital. Houston, TX, USA.
Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA
Wellcome Trust Sanger Institute. Cambridge, UK.
Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA
Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA
Radboud University Nijmegen Medical Centre.Radboud University Medical Center Institute for Molecular Life Sciences. Department of Human Genetics. Nijmegen, the Netherlands/ Maastricht University Medical Center. Department of Clinical Genetics. Maastricht, the Netherlands.
Baylor College of Medicine. Department of Molecular and Human Genetics. Houston, TX, USA/Baylor College of Medicine. Department of Pediatrics. Houston, TX, USA/ Texas Children's Hospital Houston, TX, USA/Baylor College of Medicine. Human Genome Sequencing Center. Houston, TX, USA.
Abstract
We investigated complex genomic rearrangements (CGRs) consisting of triplication copy-number variants (CNVs) that were accompanied by extended regions of copy-number-neutral absence of heterozygosity (AOH) in subjects with multiple congenital abnormalities. Molecular analyses provided observational evidence that in humans, post-zygotically generated CGRs can lead to regional uniparental disomy (UPD) due to template switches between homologs versus sister chromatids by using microhomology to prime DNA replication—a prediction of the replicative repair model, MMBIR. Our findings suggest that replication-based mechanisms might underlie the formation of diverse types of genomic alterations (CGRs and AOH) implicated in constitutional disorders
Keywords
DNA Copy Number Variations/geneticsModels, Genetic
Polymorphism, Single Nucleotide/genetics
Sequence Analysis, DNA
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