title: A 500-kb region on chromosome 16p13.1 contains the pseudoxanthoma elasticum locus: high-resolution mapping and genomic structure.
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 16p 13.1. 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 PKDI) 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.
authors.affiliation: Department of Cardiology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: L
authors.initials: L
authors.lastname: Cai
authors.forename: B
authors.initials: B
authors.lastname: Struk
authors.forename: M D
authors.initials: MD
authors.lastname: Adams
authors.forename: W
authors.initials: W
authors.lastname: Ji
authors.forename: T
authors.initials: T
authors.lastname: Haaf
authors.forename: H L
authors.initials: HL
authors.lastname: Kang
authors.forename: S H
authors.initials: SH
authors.lastname: Dho
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.forename: F
authors.initials: F
authors.lastname: Ringpfeil
authors.forename: J
authors.initials: J
authors.lastname: Nancarrow
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authors.initials: S
authors.lastname: Zäch
authors.forename: L
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authors.lastname: Schaen
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authors.lastname: Stumm
authors.forename: T
authors.initials: T
authors.lastname: Niu
authors.forename: J
authors.initials: J
authors.lastname: Chung
authors.forename: K
authors.initials: K
authors.lastname: Lunze
authors.forename: B
authors.initials: B
authors.lastname: Verrecchia
authors.forename: L A
authors.initials: LA
authors.lastname: Goldsmith
authors.forename: D
authors.initials: D
authors.lastname: Viljoen
authors.forename: L E
authors.initials: LE
authors.lastname: Figuera
authors.forename: W
authors.initials: W
authors.lastname: Fuchs
authors.forename: M
authors.initials: M
authors.lastname: Lebwohl
authors.forename: J
authors.initials: J
authors.lastname: Uitto
authors.forename: R
authors.initials: R
authors.lastname: Richards
authors.forename: D
authors.initials: D
authors.lastname: Hohl
authors.forename: R
authors.initials: R
authors.lastname: Ramesar
mesh_terms: D000328:Adult; D000818:Animals; D018244:Chromosomes, Artificial, Yeast; D002885:Chromosomes, Human, Pair 16; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D051379:Mice; D018895:Microsatellite Repeats; D010375:Pedigree; D020161:Physical Chromosome Mapping; D016133:Polymerase Chain Reaction; D011561:Pseudoxanthoma Elasticum / Q000235:genetics*