Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. 1986 Jun; 83(12): 4408–4412.
PMCID: PMC323742

Isolation of molecular probes associated with the chromosome 15 instability in the Prader-Willi syndrome.


Flow cytometry and recombinant DNA techniques have been used to obtain reagents for a molecular analysis of the Prader-Willi syndrome (PWS). HindIII total-digest libraries were prepared in lambda phage Charon 21A from flow-sorted inverted duplicated no. 15 human chromosomes and propagated on recombination-proficient (LE392) and recBC-, sbcB- (DB1257) bacteria. Twelve distinct chromosome 15-specific probes have been isolated. Eight localized to the region 15q11----13. Four of these eight sublocalized to band 15q11.2 and are shown to be deleted in DNA of one of two patients examined with the PWS. Heteroduplex analysis of two of these clones, which grew on DB1257 but not on LE392, revealed stem-loop structures in the inserts, indicative of inverted, repeated DNA elements. Such DNA repeats might account for some of the cloning instability of DNA segments from proximal 15q. Analysis of the genetic and physical instability associated with the repeated sequences we have isolated from band 15q11.2 may elucidate the molecular basis for the instability of this chromosomal region in patients with the PWS or other diseases associated with chromosomal abnormalities in the proximal long arm of human chromosome 15.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Ledbetter DH, Riccardi VM, Airhart SD, Strobel RJ, Keenan BS, Crawford JD. Deletions of chromosome 15 as a cause of the Prader-Willi syndrome. N Engl J Med. 1981 Feb 5;304(6):325–329. [PubMed]
  • Ledbetter DH, Mascarello JT, Riccardi VM, Harper VD, Airhart SD, Strobel RJ. Chromosome 15 abnormalities and the Prader-Willi syndrome: a follow-up report of 40 cases. Am J Hum Genet. 1982 Mar;34(2):278–285. [PMC free article] [PubMed]
  • Mattei JF, Mattei MG, Giraud F. Prader-Willi syndrome and chromosome 15. A clinical discussion of 20 cases. Hum Genet. 1983;64(4):356–362. [PubMed]
  • Mattei MG, Souiah N, Mattei JF. Chromosome 15 anomalies and the Prader-Willi syndrome: cytogenetic analysis. Hum Genet. 1984;66(4):313–334. [PubMed]
  • Fraccaro M, Zuffardi O, Bühler E, Schinzel A, Simoni G, Witkowski R, Bonifaci E, Caufin D, Cignacco G, Delendi N, et al. Deficiency, transposition, and duplication of one 15q region may be alternatively associated with Prader-Willi (or a similar) syndrome. Analysis of seven cases after varying ascertainment. Hum Genet. 1983;64(4):388–394. [PubMed]
  • Wisniewski LP, Witt ME, Ginsberg-Fellner F, Wilner J, Desnick RJ. Prader-Willi syndrome and a bisatellited derivative of chromosome 15. Clin Genet. 1980 Jul;18(1):42–47. [PubMed]
  • de France HF, Beemer FA, Ippel PF. Duplication in chromosome 15q in a boy with the Prader-Willi syndrome; further cytogenetic confusion. Clin Genet. 1984 Oct;26(4):379–382. [PubMed]
  • Young BD. Chromosome analysis by flow cytometry: a review. Basic Appl Histochem. 1984;28(1):9–19. [PubMed]
  • Stetten G, Sroka-Zaczek B, Corson VL. Prenatal detection of an accessory chromosome identified as an inversion duplication (15). Hum Genet. 1981;57(4):357–359. [PubMed]
  • Lalande M, Schreck RR, Hoffman R, Latt SA. Identification of inverted duplicated #15 chromosomes using bivariate flow cytometric analysis. Cytometry. 1985 Jan;6(1):1–6. [PubMed]
  • Wyman AR, Wolfe LB, Botstein D. Propagation of some human DNA sequences in bacteriophage lambda vectors requires mutant Escherichia coli hosts. Proc Natl Acad Sci U S A. 1985 May;82(9):2880–2884. [PMC free article] [PubMed]
  • Nader WF, Edlind TD, Huettermann A, Sauer HW. Cloning of Physarum actin sequences in an exonuclease-deficient bacterial host. Proc Natl Acad Sci U S A. 1985 May;82(9):2698–2702. [PMC free article] [PubMed]
  • Benton WD, Davis RW. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. [PubMed]
  • Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. [PubMed]
  • Feinberg AP, Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. [PubMed]
  • Sealey PG, Whittaker PA, Southern EM. Removal of repeated sequences from hybridisation probes. Nucleic Acids Res. 1985 Mar 25;13(6):1905–1922. [PMC free article] [PubMed]
  • Litt M, White RL. A highly polymorphic locus in human DNA revealed by cosmid-derived probes. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6206–6210. [PMC free article] [PubMed]
  • Tantravahi U, Kirschner DA, Beauregard L, Page L, Kunkel L, Latt S. Cytologic and molecular analysis of 46,XXq- cells to identify a DNA segment that might serve as a probe for a putative human X chromosome inactivation center. Hum Genet. 1983;64(1):33–38. [PubMed]
  • Bruns GA, Mintz BJ, Leary AC, Regina VM, Gerald PS. Human lysosomal genes: arylsulfatase A and beta-galactosidase. Biochem Genet. 1979 Dec;17(11-12):1031–1059. [PubMed]
  • Harper ME, Saunders GF. Localization of single copy DNA sequences of G-banded human chromosomes by in situ hybridization. Chromosoma. 1981;83(3):431–439. [PubMed]
  • Donlon TA, Litt M, Newcom SR, Magenis RE. Localization of the restriction fragment length polymorphism D14S1 (pAW-101) to chromosome 14q32.1 leads to 32.2 by in situ hybridization. Am J Hum Genet. 1983 Nov;35(6):1097–1106. [PMC free article] [PubMed]
  • Westmoreland BC, Szybalski W, Ris H. Mapping of deletions and substitutions in heteroduplex DNA molecules of bacteriophage lambda by electron microscopy. Science. 1969 Mar 21;163(3873):1343–1348. [PubMed]
  • Brunk CF, Jones KC, James TW. Assay for nanogram quantities of DNA in cellular homogenates. Anal Biochem. 1979 Jan 15;92(2):497–500. [PubMed]
  • Lalande M, Dryja TP, Schreck RR, Shipley J, Flint A, Latt SA. Isolation of human chromosome 13-specific DNA sequences cloned from flow sorted chromosomes and potentially linked to the retinoblastoma locus. Cancer Genet Cytogenet. 1984 Dec;13(4):283–295. [PubMed]
  • Houck CM, Rinehart FP, Schmid CW. A ubiquitous family of repeated DNA sequences in the human genome. J Mol Biol. 1979 Aug 15;132(3):289–306. [PubMed]
  • Schmid CW, Jelinek WR. The Alu family of dispersed repetitive sequences. Science. 1982 Jun 4;216(4550):1065–1070. [PubMed]
  • Schreck RR, Breg WR, Erlanger BF, Miller OJ. Preferential derivation of abnormal human G-group-like chromosomes from chromosome 15. Hum Genet. 1977 Apr 7;36(1):1–12. [PubMed]
  • Botstein D, White RL, Skolnick M, Davis RW. Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet. 1980 May;32(3):314–331. [PMC free article] [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • OMIM
    OMIM record citing PubMed
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...