Absence of heterozygosity due to template switching during replicative rearrangements.

Authors :: Carvalho CM
Pfundt R
King DA
Lindsay SJ
Zuccherato LW
Macville MV
Liu P
Johnson D
Stankiewicz P
Brown CW
Shaw CA
Hurles ME
Ira G
Hastings PJ
Brunner HG
Lupski JR
Source :: American journal of human genetics [Am J Hum Genet] 2015 Apr 02; Vol. 96 (4), pp. 555-64. Date of Electronic Publication: 2015 Mar 19.
Publication Year :: 2015
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.<br /> (Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Subjects :: Base Sequence
Humans
In Situ Hybridization, Fluorescence
Molecular Sequence Data
Netherlands
Polymerase Chain Reaction
Polymorphism, Single Nucleotide genetics
Sequence Analysis, DNA
DNA Copy Number Variations genetics
DNA Repair genetics
DNA Replication genetics
Gene Rearrangement genetics
Loss of Heterozygosity genetics
Models, Genetic
Uniparental Disomy genetics

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