Absence of Heterozygosity Due to Template Switching during Replicative Rearrangements

作者：Carvalho Claudia M B; Pfundt Rolph; King Daniel A; Lindsay Sarah J; Zuccherato Luciana W; Macville Merryn V E; Liu Pengfei; Johnson Diana; Stankiewicz Pawel; Brown Chester W; Shaw Chad A; Hurles Matthew E; Ira Grzegorz; Hastings P J; Brunner Han G; Lupski James R^*

来源：American Journal of Human Genetics, 2015, 96(4): 555-564.

DOI：10.1016/j.ajhg.2015.01.021

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.

• 出版日期2015-4-2