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

Citation
L. Cai et al., A 500-kb region on chromosome 16p13.1 contains the pseudoxanthoma elasticum locus: high-resolution mapping and genomic structure, J MOL MED-J, 78(1), 2000, pp. 36-46
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Journal title
JOURNAL OF MOLECULAR MEDICINE-JMM
ISSN journal
0946-2716 → ACNP
Volume
78
Issue
1
Year of publication
2000
Pages
36 - 46
Database
ISI
SICI code
0946-2716(2000)78:1<36:A5ROC1>2.0.ZU;2-M
Abstract
We have recently mapped the genetic defect underlying pseudoxanthoma elasti cum (PXE), an inherited disorder characterized by progressive calcification of elastic fibers in skin, eye, and cardiovascular system, to chromosome 1 6p13.1. Here we report further data on the fine-mapping and genomic structu re of this locus. Haplotype analysis of informative PXE families narrowed t he locus to an interval of less than 500 kb located between markers D16B962 1 and D16S764. Three overlapping YAC clones were found to cover this region through YAC-STS content mapping. An overlapping BAC contig was then constr ucted 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 int erval. By screening a somatic cell hybrid panel we were able to precision-m ap the breakpoint of Cy185 and the starting point of a chromosomal duplicat ion within 20 kb of BAC A962B4. The present data further refine the localiz ation of PXE, provide additional physical cloning resources, and will aid i n the eventual identification of the genetic defect causing PXE.