Multiple regulatory variants located in cell type-specific enhancers within the PKP2 locus form major risk and protective haplotypes for canine atopic dermatitis in German shepherd dogs.

BACKGROUND Canine atopic dermatitis (CAD) is a chronic inflammatory skin disease triggered by allergic reactions involving IgE antibodies directed towards environmental allergens. We previously identified a ~1.5 Mb locus on canine chromosome 27 associated with CAD in German shepherd dogs (GSDs). Fine-mapping indicated association closest to the PKP2 gene encoding plakophilin 2. RESULTS Additional genotyping and association analyses in GSDs combined with control dogs from five breeds with low-risk for CAD revealed the top SNP 27:19,086,778 (p = 1.4 × 10(-7)) and a rare ~48 kb risk haplotype overlapping the PKP2 gene and shared only with other high-risk CAD breeds. We selected altogether nine SNPs (four top-associated in GSDs and five within the ~48 kb risk haplotype) that spanned ~280 kb forming one risk haplotype carried by 35 % of the GSD cases and 10 % of the GSD controls (OR = 5.1, p = 5.9 × 10(-5)), and another haplotype present in 85 % of the GSD cases and 98 % of the GSD controls and conferring a protective effect against CAD in GSDs (OR = 0.14, p = 0.0032). Eight of these SNPs were analyzed for transcriptional regulation using reporter assays where all tested regions exerted regulatory effects on transcription in epithelial and/or immune cell lines, and seven SNPs showed allelic differences. The DNA fragment with the top-associated SNP 27:19,086,778 displayed the highest activity in keratinocytes with 11-fold induction of transcription by the risk allele versus 8-fold by the control allele (pdifference = 0.003), and also mapped close (~3 kb) to an ENCODE skin-specific enhancer region. CONCLUSIONS Our experiments indicate that multiple CAD-associated genetic variants located in cell type-specific enhancers are involved in gene regulation in different cells and tissues. No single causative variant alone, but rather multiple variants combined in a risk haplotype likely contribute to an altered expression of the PKP2 gene, and possibly nearby genes, in immune and epithelial cells, and predispose GSDs to CAD.

Shoreline plant establishment and use of a wave-stilling device /

"January 1978."

Seed list : a list of forage plant seeds and the incidental seeds commonly found with them.

Cover title.

Radioisotopes in agriculture : analytical procedures, animal husbandry, entomology, fertilizer uptake, general studies, photosynthesis, plant genetics, and plant physiology : a selected bibliography /

"TID-3078(Suppl. 1). Biology and Medicine, TID-4500 (31st edition)."

National plant, flower and fruit guild magazine,

Mode of access: Internet.

Soviet publications in plant pathology and closely related fields; titles published from 1925 through early 1953 and available in the Library of the U.S. Department of Agriculture.

Mode of access: Internet.

Wisconsin soil testing plant analysis and feed and forage analysis procedures /

"Revised 1977"--cover.

Report and recommendations of the Plant Science and Entomology Research Advisory Committee : developed at its meeting, February 6-10, 1967, Wheaton, Maryland.

Mode of access: Internet.

A reference guide to federal plant quarantines and regulations administered by the Plant Quarantine Division.

Description based on: No. 2 published December 1970; title from cover.

Report on the school plant survey and the school building program for City of Reading, Berks county, Pennsylvania ...

Mode of access: Internet.

Wood's illustrated plant record and guide to analysis. Adapted to any American botany.

Mode of access: Internet.

A botanical survey of U.S. route 45 [FAP 332, section 31-1, 42-1], from Harrisburg to Eldorado [from IL route 13 to IL route 142], Saline County, Illinois, with emphasis on threatened and endangered plant species and natural areas /

Cover title.

The flower and the bee; plant life and pollination,

Mode of access: Internet.

Organizational maintenance repair parts and special tools lists : crusher, roll, diesel and electric driven, wheel mounted, pneumatic tires, 75 ton per hour, NSN 3820-00-788-5999, Eagle crusher model 5230B, NSN 3820-00-876-7876, Eagle crusher model 5230C and model 5230D, component of crushing and screening plant, diesel and electric driven, wheel mounted, 75 ton per hour.

Includes index.