title: 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.
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.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, Oxford, OX3 7BN, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Monk
authors.forename: A
authors.initials: A
authors.lastname: Sakuntabhai
authors.forename: S A
authors.initials: SA
authors.lastname: Carter
authors.forename: S D
authors.initials: SD
authors.lastname: Bryce
authors.forename: R
authors.initials: R
authors.lastname: Cox
authors.forename: L
authors.initials: L
authors.lastname: Harrington
authors.forename: E
authors.initials: E
authors.lastname: Levy
authors.forename: V L
authors.initials: VL
authors.lastname: Ruiz-Perez
authors.forename: E
authors.initials: E
authors.lastname: Katsantoni
authors.forename: A
authors.initials: A
authors.lastname: Kodvawala
authors.forename: C S
authors.initials: CS
authors.lastname: Munro
authors.forename: S
authors.initials: S
authors.lastname: Burge
authors.forename: M
authors.initials: M
authors.lastname: Larrègue
authors.forename: G
authors.initials: G
authors.lastname: Nagy
authors.forename: J L
authors.initials: JL
authors.lastname: Rees
authors.forename: M
authors.initials: M
authors.lastname: Lathrop
authors.forename: A P
authors.initials: AP
authors.lastname: Monaco
authors.forename: T
authors.initials: T
authors.lastname: Strachan
authors.forename: A
authors.initials: A
authors.lastname: Hovnanian
mesh_terms: D002874:Chromosome Mapping; D018244:Chromosomes, Artificial, Yeast; D002876:Chromosomes, Bacterial; D002881:Chromosomes, Human, Pair 12; D004274:DNA, Recombinant; D007644:Darier Disease / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D010375:Pedigree
chemical_list: D004274:DNA, Recombinant