Abstract
The most prevalent microdeletion in humans occurs at 22q11.2, a region rich in chromosome-specific low copy repeats (LCR22s). The structure of this region has defied elucidation due to its size, regional complexity, and haplotype diversity, and is not well represented in the human genome reference. Most individuals with 22q11.2 deletion syndrome (22q11.2DS) carry a de novo hemizygous deletion of ~ 3 Mbp occurring by non-allelic homologous recombination (NAHR) mediated by LCR22s. In this study, optical mapping has been used to elucidate LCR22 structure and variation in 88 individuals in thirty 22q11.2DS families to uncover potential risk factors for germline rearrangements leading to 22q11.2DS offspring. Families were optically mapped to characterize LCR22 structures, NAHR locations, and genomic signatures associated with the deletion. Bioinformatics analyses revealed clear delineations between LCR22 structures in normal and deletion-containing haplotypes. Despite no explicit whole-haplotype predisposing configurations being identified, all NAHR events contain a segmental duplication encompassing FAM230 gene members suggesting preferred recombination sequences. Analysis of deletion breakpoints indicates that preferred recombinat...Continue Reading
References
Aug 21, 1992·Cell·C MézardA Nicolas
Oct 5, 1990·Journal of Molecular Biology·S F AltschulD J Lipman
Sep 11, 1998·Journal of Medical Genetics·K DevriendtK Keymolen
Jun 17, 1999·Human Molecular Genetics·L EdelmannB E Morrow
Mar 4, 2000·Human Molecular Genetics·T H ShaikhB S Emanuel
Jun 5, 2002·Genome Research·W James KentDavid Haussler
Aug 10, 2002·Science·Jeffrey A BaileyEvan E Eichler
Mar 14, 2003·European Journal of Human Genetics : EJHG·Gabriel Stefan GebhardtMarc Gewillig
Mar 9, 2005·American Journal of Medical Genetics. Part a·Donna M McDonald-McGinnElaine H Zackai
Oct 28, 2005·Genome Research·Adam PavlicekBernice E Morrow
Apr 18, 2006·European Journal of Human Genetics : EJHG·N Simon ThomasPatricia A Jacobs
Mar 14, 2007·Genome Research·Tamim H ShaikhSulagna C Saitta
Feb 23, 2008·Genome Research·Ivon CuscóLuis A Pérez-Jurado
Jul 19, 2008·Developmental Disabilities Research Reviews·Beverly S Emanuel
Jul 7, 2009·Human Molecular Genetics·Lisenka E L M VissersPawel Stankiewicz
Aug 24, 2010·Nature Genetics·Francesca AntonacciEvan E Eichler
Oct 11, 2011·American Journal of Human Genetics·Pengfei LiuJames R Lupski
Mar 22, 2013·PLoS Genetics·Hannah VerdinElfride De Baere
Nov 15, 2013·Bioinformatics·Brian J RaneyW James Kent
May 13, 2015·Prenatal Diagnosis·Francesca Romana GratiFrançois Vialard
Mar 1, 2016·Nature Reviews. Genetics·Claudia M B Carvalho, James R Lupski
Jan 1, 2015·Nature Reviews. Disease Primers·Donna M McDonald-McGinnAnne S Bassett
Jul 21, 2016·Human Molecular Genetics·Xingyi GuoDeyou Zheng
Mar 6, 2019·Nature Communications·Michal Levy-SakinPui-Yan Kwok
Sep 5, 2019·Genome Research·Wolfram DemaerelJoris R Vermeesch
Citations
Aug 28, 2020·Genes·Małgorzata Karbarz
Dec 18, 2020·Nature Reviews. Cancer·Jeffery M Klco, Charles G Mullighan
Apr 4, 2021·Genes·Nikhil Shri SahajpalAlka Chaubey
Jul 8, 2021·Analytical Chemistry·Lahari UppuluriMing Xiao
Aug 3, 2021·Frontiers in Genetics·Lisanne VervoortJoris R Vermeesch
Oct 5, 2021·Frontiers in Genetics·Heming WuZhixiong Zhong