Refined Genetic Mapping of the Darier Locus to a !1-cM Region of Chromosome 12q24.1, and Construction of a Complete, High-Resolution P1 Artificial Chromosome/Bacterial Artificial Chromosome Contig of the Critical Region

Anavaj Sakuntabhai, Sarah Monk, Simon A. Carter, Steven D. Bryce, Roger Cox, Louise Harrington, Elaine Levy, Victor L. Ruiz-Perez, Eleni Katsantoni, Ahmer Kodvawala, Colin S. Munro, Susan Burge, Marc Larrègue, Gyula Nagy, Jonathan L. Rees, Mark Lathrop, Anthony P. Monaco, Tom Strachan, Alain Hovnanian

Research output: Contribution to journalArticle

Abstract

Darier disease (DD) (MIM 124200) is an autosomal
dominant skin disorder characterized by loss of adhesion
between epidermal cells and by abnormal keratinization.
We present linkage analysis showing, in four families,
key recombination events that refine the location of the
DD locus on chromosome 12q23-24.1 to a region of
!1 cM. We have constructed a YAC/P1 artificial
chromosome (PAC)/bacterial artificial chromosome
(BAC)–based physical map that encompasses this refined
DD region. The map consists of 35 YAC, 69 PAC, 16
BAC, and 2 cosmid clones that were ordered by mapping
54 anonymous sequence-tagged sites. The critical region
is estimated to be 2.4 Mb in size, with an average marker
resolution of 37.5 kb. The refinement of the critical interval
excludes the ALDH2, RPL6, PTPN11, and OAS
genes, as well as seven expressed sequence tags (ESTs)
previously mapped in the DD region. The three known
genes (ATP2A2, PPP1CC, and SCA2) and the 10 ESTs
mapped within the critical region are not obvious candidates
for the DD gene. Therefore, this detailed integrated
physical, genetic, and partial transcript map provides
an important resource for the isolation of the DD
gene and, possibly, other disease genes.
Original languageEnglish
Pages (from-to)890-903
JournalAmerican Journal of Human Genetics
Volume62
Issue number4
DOIs
Publication statusPublished - 22 Jan 1998

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