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

• Published in: American journal of human genetics Vol. 62; no. 4; pp. 890 - 903
• Main Authors: Monk, Sarah, Sakuntabhai, Anavaj, Carter, Simon A., Bryce, Steven D., Cox, Roger, Harrington, Louise, Levy, Elaine, Ruiz-Perez, Victor L., Katsantoni, Eleni, Kodvawala, Ahmer, Munro, Colin S., Burge, Susan, Larrègue, Marc, Nagy, Gyula, Rees, Jonathan L., Lathrop, Mark, Monaco, Anthony P., Strachan, Tom, Hovnanian, Alain
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01-04-1998; University of Chicago Press
• Subjects: Bacterial artificial chromosome contig; Biological and medical sciences; Chromosome 12; Chromosome Mapping; Chromosomes, Artificial, Yeast; Chromosomes, Bacterial; Chromosomes, Human, Pair 12; Darier disease; Darier Disease - genetics; Dermatology; DNA, Recombinant; Female; Haplotypes; Hereditary diseases of the skin. Congenital diseases of the skin. Haemangioma of the skin, of mucosae and of soft tissue; Humans; Male; Mapping, refined; Medical sciences; P1 artificial chromosome contig; Pedigree; YAC contig; P1 artificial chromosome contig; Bacterial artificial chromosome contig; Chromosome 12; YAC contig; Darier disease; Mapping, refined; Genetic mapping; Human; Skin disease; High resolution; Linkage; Family study; Hyperkeratosis; Chromosome C12; Artificial chromosome; Genetic determinism; Genetic disease; Gene; Cytogenetics; Technique; Molecular biology; Locus
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/301794

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.