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Journal of Molecular Medicine

, Volume 78, Issue 1, pp 36–46 | Cite as

A 500-kb region on chromosome 16p13.1 contains the pseudoxanthoma elasticum locus: high-resolution mapping and genomic structure

  • Li Cai
  • Berthold Struk
  • Mark D. Adams
  • Wan Ji
  • Thomas Haaf
  • Hyung-Lyun Kang
  • So Hee Dho
  • Xuequn Xu
  • Franziska Ringpfeil
  • Julie Nancarrow
  • Stéphanie Zäch
  • Lori Schaen
  • Markus Stumm
  • Tianhua Niu
  • Joon Chung
  • Karsten Lunze
  • Bradford Verrecchia
  • Lowell A. Goldsmith
  • Denis Viljoen
  • Luis E. Figuera
  • Wayne Fuchs
  • Mark Lebwohl
  • Jouni Uitto
  • Robert Richards
  • Daniel Hohl
  • Raj Ramesar
  • David F. Callen
  • Ung-Jin Kim
  • Norman A. Doggett
  • Kenneth H. Neldner
  • Klaus Lindpaintner
Original Article

Abstract.

We have recently mapped the genetic defect underlying pseudoxanthoma elasticum (PXE), an inherited disorder characterized by progressive calcification of elastic fibers in skin, eye, and cardiovascular system, to chromosome 16p13.1. Here we report further data on the fine-mapping and genomic structure of this locus. Haplotype analysis of informative PXE families narrowed the locus to an interval of less than 500 kb located between markers D16B9621 and D16S764. Three overlapping YAC clones were found to cover this region through YAC-STS content mapping. An overlapping BAC contig was then constructed to cover this interval and the surrounding region. About 80% of this chromosomal region has been fully sequenced using the BAC shotgun technique. Gene content and sequence analysis predicted four genes (MRP1, MRP6, PM5, and a novel transcript) and two pseudogenes (ARA and PKD1) within this interval. By screening a somatic cell hybrid panel we were able to precision-map the breakpoint of Cy185 and the starting point of a chromosomal duplication within 20 kb of BAC A962B4. The present data further refine the localization of PXE, provide additional physical cloning resources, and will aid in the eventual identification of the genetic defect causing PXE.

Pseudoxanthoma elasticum Genetic mapping Physical mapping BAC contigs YAC contigs 

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Copyright information

© Springer-Verlag 2000

Authors and Affiliations

  • Li Cai
    • 1
  • Berthold Struk
    • 1
  • Mark D. Adams
    • 3
  • Wan Ji
    • 1
  • Thomas Haaf
    • 15
  • Hyung-Lyun Kang
    • 4
  • So Hee Dho
    • 4
  • Xuequn Xu
    • 4
  • Franziska Ringpfeil
    • 7
  • Julie Nancarrow
    • 6
  • Stéphanie Zäch
    • 11
  • Lori Schaen
    • 12
  • Markus Stumm
    • 16
  • Tianhua Niu
    • 1
  • Joon Chung
    • 1
  • Karsten Lunze
    • 1
  • Bradford Verrecchia
    • 1
  • Lowell A. Goldsmith
    • 12
  • Denis Viljoen
    • 14
  • Luis E. Figuera
    • 13
  • Wayne Fuchs
    • 10
  • Mark Lebwohl
    • 8
  • Jouni Uitto
    • 7
  • Robert Richards
    • 6
  • Daniel Hohl
    • 11
  • Raj Ramesar
    • 9
  • David F. Callen
    • 6
  • Ung-Jin Kim
    • 4
  • Norman A. Doggett
    • 5
  • Kenneth H. Neldner
    • 2
  • Klaus Lindpaintner
    • 1
  1. 1.Department of Cardiology, Children's Hospital, Cardiovascular Division, Brigham and Women's Hospital, Departments of Cardiology and Medicine, Harvard Medical School, Boston, MA 02115, USAUSA
  2. 2.Department of Dermatology, Health Sciences Center, Texas Tech University, Lubbock, TX 79430, USAUSA
  3. 3.Institute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850, USAUSA
  4. 4.Caltech Genome Research Laboratory, Division of Biology, California Institute of Technology, Pasadena, CA 91125, USAUSA
  5. 5.Life Sciences Division and Center for Human Genome Studies, Los Alamos National Laboratory, Los Alamos, NM 87545, USAUSA
  6. 6.Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, 71 King William Road, North Adelaide S.A. 5006, AustraliaAustralia
  7. 7.Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USAUSA
  8. 8.Department of Dermatology, Mount Sinai School of Medicine, New York, NY 10029, USAUSA
  9. 9.Department of Human Genetics, Medical School, University of Cape Town, Observatory 7925, South AfricaSouth Africa
  10. 10.Department of Ophthalmology, Mount Sinai School of Medicine, New York, NY 10029, USAUSA
  11. 11.Department of Dermatology, University of Lausanne, 1011 Lausanne, SwitzerlandSwitzerland
  12. 12.Department of Dermatology, University of Rochester, Rochester, NY 14642, USAUSA
  13. 13.Divisions of Genetics and Molecular Medicine, CIBO-IMSS, University of Guadalajara Medical School, Guadalajara, Jal MexicoMexico
  14. 14.South African Institute for Medical Research, JohannesburgSouth Africa
  15. 15.Max Plank Institute for Molecular Genetics, Berlin, GermanyGermany
  16. 16.Human Genetics Institute, Otto von Guericke University, Magdeburg, GermanyGermany

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