Molecular characterization of two proximal deletion breakpoint regions in both Prader-Willi and Angelman syndrome patients

S. L. Christian, W. P. Robinson, B. Huang, A. Mutirangura, M. R. Line, M. Nakao, U. Surti, A. Chakravarti, D. H. Ledbetter

Research output: Contribution to journalArticle

Abstract

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct mental retardation syndromes caused by paternal and maternal deficiencies, respectively, in chromosome 15q11-q13. Approximately 70% of these patients have a large deletion of ~4 Mb extending from D15S9 (ML34) through D15S12 (IR10). To further characterize the deletion breakpoints proximal to D1589, three new polymorphic microsatellite markers were developed that showed observed heterozygosities of 60%-87%. D15S541 and D15S542 were isolated from YAC A124A3 containing the D15S18 (IR39) locus. D15S543 was isolated from a cosmid cloned from the proximal right end of YAC 254B5 containing the D15S9 (ML34) locus. Gene-centromere mapping of these markers, using a panel of ovarian teratomas of known meiotic origin, extended the genetic map of chromosome 15 by 2-3 cM toward the centromere. Analysis of the more proximal S541/S542 marken on 53 Prader-Willi and 33 Angelman deletion patients indicated two classes of patients: 44% (35/80) of the informative patients were deleted for these marken (class I), while 56% (45/80) were not deleted (class II), with no difference between PWS and AS. In contrast, D15S543 was deleted in all informative patients (13/48) or showed the presence of a single allele (in 35/48 patients), suggesting that this marker is deleted in the majority of PWS and AS cases. These results confirm the presence of two common proximal deletion breakpoint regions in both Prader-Willi and Angelman syndromes and are consistent with the same deletion mechanism being responsible for paternal and maternal deletions. One breakpoint region lies between D15S541/S542 and D15S543, with an additional breakpoint region being proximal to D15S541/S542.

Original languageEnglish (US)
Pages (from-to)40-48
Number of pages9
JournalAmerican journal of human genetics
Volume57
Issue number1
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Christian, S. L., Robinson, W. P., Huang, B., Mutirangura, A., Line, M. R., Nakao, M., Surti, U., Chakravarti, A., & Ledbetter, D. H. (1995). Molecular characterization of two proximal deletion breakpoint regions in both Prader-Willi and Angelman syndrome patients. American journal of human genetics, 57(1), 40-48.