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Journal article
The 22q11 low copy repeats are characterized by unprecedented size and structural variability
Genome research, v 29(9), pp 1389-1401
Sep 2019
PMID: 31481461
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- The 22q11 low copy repeats are characterized by unprecedented size and structural variability
- Creators
- Wolfram Demaerel - Departement of Human Genetics, KU Leuven, Leuven, 3000 Belgium.Yulia Mostovoy - University of California, San FranciscoFeyza Yilmaz - University of Colorado Anschutz Medical CampusLisanne Vervoort - Departement of Human Genetics, KU Leuven, Leuven, 3000 Belgium.Steven Pastor - Children's Hospital of PhiladelphiaMatthew S Hestand - Cincinnati Children's Hospital Medical CenterAnn Swillen - Departement of Human Genetics, KU Leuven, Leuven, 3000 Belgium.Elfi Vergaelen - Departement of Human Genetics, KU Leuven, Leuven, 3000 Belgium.Elizabeth A Geiger - University of Colorado DenverCurtis R Coughlin - University of Colorado DenverStephen K Chow - University of California, San FranciscoDonna McDonald-McGinn - Children's Hospital of PhiladelphiaBernice Morrow - Albert Einstein College of MedicinePui-Yan Kwok - University of California, San FranciscoMing Xiao - Drexel UniversityBeverly S Emanuel - Children's Hospital of PhiladelphiaTamim H Shaikh - University of Colorado DenverJoris R Vermeesch - Departement of Human Genetics, KU Leuven, Leuven, 3000 Belgium.
- Publication Details
- Genome research, v 29(9), pp 1389-1401
- Publisher
- American Physical Society (APS)
- Grant note
- U01 MH101720 / NIMH NIH HHS U54 HD090260 / NICHD NIH HHS R01 HL084410 / NHLBI NIH HHS P01 HD070454 / NICHD NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000484362700002
- Scopus ID
- 2-s2.0-85071764815
- Other Identifier
- 991019167931104721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Biotechnology & Applied Microbiology
- Genetics & Heredity