Absence of heterozygosity due to template switching during replicative rearrangements.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 25799105.
- Also identified by DOI 10.1016/j.ajhg.2015.01.021 and PMC identifier 4385179.
- No licence information is recorded for this record.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
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.
Medical subject headings
- DNA Copy Number Variations
- DNA Repair
- DNA Replication
- Gene Rearrangement
- Loss of Heterozygosity
- Models, Genetic
- Uniparental Disomy