The 22q11 low copy repeats are characterized by unprecedented size and structural variability

Wolfram Demaerel, Yulia Mostovoy, Feyza Yilmaz, Lisanne Vervoort, Steven Pastor, Matthew S. Hestand, Ann Swillen, Elfi Vergaelen, Elizabeth A. Geiger, Curtis R. Coughlin, Stephen K. Chow, Donna McDonald-McGinn, Bernice E. Morrow, Pui Yan Kwok, Ming Xiao, Beverly S. Emanuel, Tamim H. Shaikh, Joris R. Vermeesch

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1389-1401
Number of pages13
JournalGenome research
Volume29
Issue number9
DOIs
StatePublished - Sep 1 2019

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22q11 Deletion Syndrome
Genomic Segmental Duplications
Homologous Recombination
Alleles
Genome
Chromosomes, Human, Pair 22
Genomic Instability
Parents
Cell Line
Incidence
Population

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Demaerel, W., Mostovoy, Y., Yilmaz, F., Vervoort, L., Pastor, S., Hestand, M. S., ... Vermeesch, J. R. (2019). The 22q11 low copy repeats are characterized by unprecedented size and structural variability. Genome research, 29(9), 1389-1401. https://doi.org/10.1101/gr.248682.119

The 22q11 low copy repeats are characterized by unprecedented size and structural variability. / Demaerel, Wolfram; Mostovoy, Yulia; Yilmaz, Feyza; Vervoort, Lisanne; Pastor, Steven; Hestand, Matthew S.; Swillen, Ann; Vergaelen, Elfi; Geiger, Elizabeth A.; Coughlin, Curtis R.; Chow, Stephen K.; McDonald-McGinn, Donna; Morrow, Bernice E.; Kwok, Pui Yan; Xiao, Ming; Emanuel, Beverly S.; Shaikh, Tamim H.; Vermeesch, Joris R.

In: Genome research, Vol. 29, No. 9, 01.09.2019, p. 1389-1401.

Research output: Contribution to journalArticle

Demaerel, W, Mostovoy, Y, Yilmaz, F, Vervoort, L, Pastor, S, Hestand, MS, Swillen, A, Vergaelen, E, Geiger, EA, Coughlin, CR, Chow, SK, McDonald-McGinn, D, Morrow, BE, Kwok, PY, Xiao, M, Emanuel, BS, Shaikh, TH & Vermeesch, JR 2019, 'The 22q11 low copy repeats are characterized by unprecedented size and structural variability', Genome research, vol. 29, no. 9, pp. 1389-1401. https://doi.org/10.1101/gr.248682.119
Demaerel W, Mostovoy Y, Yilmaz F, Vervoort L, Pastor S, Hestand MS et al. The 22q11 low copy repeats are characterized by unprecedented size and structural variability. Genome research. 2019 Sep 1;29(9):1389-1401. https://doi.org/10.1101/gr.248682.119
Demaerel, Wolfram ; Mostovoy, Yulia ; Yilmaz, Feyza ; Vervoort, Lisanne ; Pastor, Steven ; Hestand, Matthew S. ; Swillen, Ann ; Vergaelen, Elfi ; Geiger, Elizabeth A. ; Coughlin, Curtis R. ; Chow, Stephen K. ; McDonald-McGinn, Donna ; Morrow, Bernice E. ; Kwok, Pui Yan ; Xiao, Ming ; Emanuel, Beverly S. ; Shaikh, Tamim H. ; Vermeesch, Joris R. / The 22q11 low copy repeats are characterized by unprecedented size and structural variability. In: Genome research. 2019 ; Vol. 29, No. 9. pp. 1389-1401.
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