Article
Absence of Heterozygosity due to Template Switching during Replicative Rearrangements.
Registro en:
CARVALHO, Claudia Márcia Benedetto et al. Absence of Heterozygosity due to Template Switching during Replicative Rearrangements. Am J Hum Genet., vol. 96, n. 4, p. 555-64, 2015.
0002-9297
10.1016/j.ajhg.2015.01.021
Autor
Carvalho, Claudia Márcia Benedetto de
Pfundt, Rolph
King, Daniel A.
Lindsay, Sarah J
Zuccherato, Luciana W
Macville, Merryn V E
Pengfei, Liu
Johnson, Diana
Stankiewicz, Pawel
Brown, Chester W
Shaw, Chad A.
Hurles, Matthew E.
Grzegorz, Ira
Hastings, PJ
Brunner, Han G
Lupski, James R.
Resumen
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