Article: A 1.5 million-base pair inversion polymorphism in families with Williams-Beuren syndrome

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TitleA 1.5 million-base pair inversion polymorphism in families with Williams-Beuren syndrome
AuthorsOsborne, LR4 6
Li, M7
Pober, B2
Chitayat, D4 7
Bodurtha, J3
Mandel, A6
Costa, T1
Grebe, T5
Cox, S5
Tsui, LC6 7
Scherer, SW6 7
Issue Date2001
PublisherNature Publishing Group. The Journal's web site is located at http://www.genetics.nature.com
CitationNature Genetics, 2001, v. 29 n. 3, p. 321-325 [How to Cite?]
DOI: http://dx.doi.org/10.1038/ng753
AbstractWilliams-Beuren syndrome (WBS) is most often caused by hemizygous deletion of a 1.5-Mb interval encompassing at least 17 genes at 7q11.23 (refs. 1,2). As with many other haploinsufficiency diseases, the mechanism underlying the WBS deletion is thought to be unequal meiotic recombination, probably mediated by the highly homologous DNA that flanks the commonly deleted region. Here, we report the use of interphase fluorescence in situ hybridization (FISH) and pulsed-field gel electrophoresis (PFGE) to identify a genomic polymorphism in families with WBS, consisting of an inversion of the WBS region. We have observed that the inversion is hemizygous in 3 of 11 (27%) atypical affected individuals who show a subset of the WBS phenotypic spectrum but do not carry the typical WBS microdeletion. Two of these individuals also have a parent who carries the inversion. In addition, in 4 of 12 (33%) families with a proband carrying the WBS deletion, we observed the inversion exclusively in the parent transmitting the disease-related chromosome. These results suggest the presence of a newly identified genomic variant within the population that may be associated with the disease. It may result in predisposition to primarily WBS-causing microdeletions, but may also cause translocations and inversions.
ISSN1061-4036
2011 Impact Factor: 35.532
2011 SCImago Journal Rankings: 8.923
DOIhttp://dx.doi.org/10.1038/ng753
ISI Accession Number IDWOS:000171911000020
PubMed Central IDPMC2889916
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorOsborne, LR
dc.contributor.authorLi, M
dc.contributor.authorPober, B
dc.contributor.authorChitayat, D
dc.contributor.authorBodurtha, J
dc.contributor.authorMandel, A
dc.contributor.authorCosta, T
dc.contributor.authorGrebe, T
dc.contributor.authorCox, S
dc.contributor.authorTsui, LC
dc.contributor.authorScherer, SW
dc.date.accessioned2007-09-12T03:52:12Z
dc.date.available2007-09-12T03:52:12Z
dc.date.issued2001
dc.description.abstractWilliams-Beuren syndrome (WBS) is most often caused by hemizygous deletion of a 1.5-Mb interval encompassing at least 17 genes at 7q11.23 (refs. 1,2). As with many other haploinsufficiency diseases, the mechanism underlying the WBS deletion is thought to be unequal meiotic recombination, probably mediated by the highly homologous DNA that flanks the commonly deleted region. Here, we report the use of interphase fluorescence in situ hybridization (FISH) and pulsed-field gel electrophoresis (PFGE) to identify a genomic polymorphism in families with WBS, consisting of an inversion of the WBS region. We have observed that the inversion is hemizygous in 3 of 11 (27%) atypical affected individuals who show a subset of the WBS phenotypic spectrum but do not carry the typical WBS microdeletion. Two of these individuals also have a parent who carries the inversion. In addition, in 4 of 12 (33%) families with a proband carrying the WBS deletion, we observed the inversion exclusively in the parent transmitting the disease-related chromosome. These results suggest the presence of a newly identified genomic variant within the population that may be associated with the disease. It may result in predisposition to primarily WBS-causing microdeletions, but may also cause translocations and inversions.
dc.description.naturelink_to_OA_fulltext
dc.identifier.citationNature Genetics, 2001, v. 29 n. 3, p. 321-325 [How to Cite?]
DOI: http://dx.doi.org/10.1038/ng753
dc.identifier.citeulike2289193
dc.identifier.doihttp://dx.doi.org/10.1038/ng753
dc.identifier.epage325
dc.identifier.isiWOS:000171911000020
dc.identifier.issn1061-4036
2011 Impact Factor: 35.532
2011 SCImago Journal Rankings: 8.923
dc.identifier.issue3
dc.identifier.openurl
dc.identifier.pmcidPMC2889916
dc.identifier.pmid11685205
dc.identifier.scopuseid_2-s2.0-0035179436
dc.identifier.spage321
dc.identifier.urihttp://hdl.handle.net/10722/44367
dc.identifier.volume29
dc.languageeng
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.genetics.nature.com
dc.publisher.placeUnited States
dc.relation.ispartofNature Genetics
dc.relation.referencesReferences in Scopus
dc.subject.meshInversion, chromosome
dc.subject.meshPolymorphism, genetic - genetics
dc.subject.meshWilliams syndrome - genetics
dc.subject.meshChromosomes, human, pair 7 - genetics
dc.subject.meshElectrophoresis, gel, pulsed-field
dc.titleA 1.5 million-base pair inversion polymorphism in families with Williams-Beuren syndrome
dc.typeArticle
Author Affiliations
  1. Atlantic Research Centre
  2. Yale University
  3. Virginia Commonwealth University
  4. University Health Network
  5. University of Arizona
  6. University of Toronto
  7. Hospital for Sick Children, Toronto