@article{8262d2d9a43e4de8b4d3fdfc18c68a74,
title = "The 22q11 low copy repeats are characterized by unprecedented size and structural variability",
abstract = "Low copy repeats (LCRs) are recognized as a significant source of genomic instability, driving genome variability and evolution. The Chromosome 22 LCRs (LCR22s) mediate nonallelic homologous recombination (NAHR) leading to the 22q11 deletion syndrome (22q11DS). However, LCR22s are among the most complex regions in the genome, and their structure remains unresolved. The difficulty in generating accurate maps of LCR22s has also hindered localization of the deletion end points in 22q11DS patients. Using fiber FISH and Bionano optical mapping, we assembled LCR22 alleles in 187 cell lines. Our analysis uncovered an unprecedented level of variation in LCR22s, including LCR22A alleles ranging in size from 250 to 2000 kb. Further, the incidence of various LCR22 alleles varied within different populations. Additionally, the analysis of LCR22s in 22q11DS patients and their parents enabled further refinement of the rearrangement site within LCR22A and -D, which flank the 22q11 deletion. The NAHR site was localized to a 160-kb paralog shared between the LCR22A and -D in seven 22q11DS patients. Thus, we present the most comprehensive map of LCR22 variation to date. This will greatly facilitate the investigation of the role of LCR variation as a driver of 22q11 rearrangements and the phenotypic variability among 22q11DS patients.",
author = "Wolfram Demaerel and Yulia Mostovoy and Feyza Yilmaz and Lisanne Vervoort and Steven Pastor and Hestand, {Matthew S.} and Ann Swillen and Elfi Vergaelen and Geiger, {Elizabeth A.} and Coughlin, {Curtis R.} and Chow, {Stephen K.} and Donna McDonald-McGinn and Bernice Morrow and Kwok, {Pui Yan} and Ming Xiao and Emanuel, {Beverly S.} and Shaikh, {Tamim H.} and Vermeesch, {Joris R.}",
note = "Funding Information: Excellent technical assistance was provided by O. Tran and A. Jin. The molar cell line CHM1 was kindly provided by E. Eichler. W.D. is a fellow at Katholieke Universiteit Leuven supported by Agentschap voor Innovatie door Wetenschap en Technologie (131625). This work was made possible by grants from the Katholieke Universiteit Leuven Programmafinanciering Vlaanderen (PFV/10/016) SymBioSys and project 1665 Fondation J{\'e}r{\^o}me Lejeune to J.R.V. and Geconcerteerde Onderzoeksacties (GOA/12/015) to J.R.V. and Koen Devriendt by the National Institute of Mental Health (5U01MH101723-02), by the National Institute of General Medical Sciences (GM120772 to T.H.S. and P.-Y.K.; GM125757 to B.S.E. and M.X.) and the Belgian Science Policy Office Interuniversity Attraction Poles (BELSPO-IAP) program through the project IAP P7/43-BeMGI. Funding Information: Excellent technical assistance was provided by O. Tran and A. Jin. The molar cell line CHM1 was kindly provided by E. Eichler. W.D. is a fellow at Katholieke Universiteit Leuven supported by Agentschap voor Innovatie door Wetenschap en Technologie (131625). This work was made possible by grants from the Katholieke Universiteit Leuven Programmafinanciering Vlaanderen (PFV/10/016) SymBioSys and project 1665 Fondation J?r?me Lejeune to J.R.V. and Geconcerteerde Onderzoeksacties (GOA/12/015) to J.R.V. and Koen Devriendt by the National Institute of Mental Health (5U01MH101723-02), by the National Institute of General Medical Sciences (GM120772 to T.H.S. and P.-Y.K.; GM125757 to B.S.E. and M.X.) and the Belgian Science Policy Office Interuniversity Attraction Poles (BELSPO-IAP) program through the project IAP P7/43-BeMGI.",
year = "2019",
doi = "10.1101/gr.248682.119",
language = "English (US)",
volume = "29",
pages = "1389--1401",
journal = "Genome Research",
issn = "1088-9051",
publisher = "Cold Spring Harbor Laboratory Press",
number = "9",
}