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Absence of heterozygosity due to template switching during replicative rearrangements.

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.

SUBMITTER: Carvalho CM

PROVIDER: S-EPMC4385179 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Absence of heterozygosity due to template switching during replicative rearrangements.

Carvalho Claudia M B CM Pfundt Rolph R King Daniel A DA Lindsay Sarah J SJ Zuccherato Luciana W LW Macville Merryn V E MV Liu Pengfei P Johnson Diana D Stankiewicz Pawel P Brown Chester W CW Shaw Chad A CA Hurles Matthew E ME Ira Grzegorz G Hastings P J PJ Brunner Han G HG Lupski James R JR

American journal of human genetics 20150319 4

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 prim ...[more]

PMID: 25799105

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