title: Assessment of allelic diversity in intron-containing Mal d 1 genes and their association to apple allergenicity.
abstract: BACKGROUND
  Mal d 1 is a major apple allergen causing food allergic symptoms of the oral allergy syndrome (OAS) in birch-pollen sensitised patients. The Mal d 1 gene family is known to have at least 7 intron-containing and 11 intronless members that have been mapped in clusters on three linkage groups. In this study, the allelic diversity of the seven intron-containing Mal d 1 genes was assessed among a set of apple cultivars by sequencing or indirectly through pedigree genotyping. Protein variant constitutions were subsequently compared with Skin Prick Test (SPT) responses to study the association of deduced protein variants with allergenicity in a set of 14 cultivars.
  
  
  RESULTS
  From the seven intron-containing Mal d 1 genes investigated, Mal d 1.01 and Mal d 1.02 were highly conserved, as nine out of ten cultivars coded for the same protein variant, while only one cultivar coded for a second variant. Mal d 1.04, Mal d 1.05 and Mal d 1.06 A, B and C were more variable, coding for three to six different protein variants. Comparison of Mal d 1 allelic composition between the high-allergenic cultivar Golden Delicious and the low-allergenic cultivars Santana and Priscilla, which are linked in pedigree, showed an association between the protein variants coded by the Mal d 1.04 and -1.06A genes (both located on linkage group 16) with allergenicity. This association was confirmed in 10 other cultivars. In addition, Mal d 1.06A allele dosage effects associated with the degree of allergenicity based on prick to prick testing. Conversely, no associations were observed for the protein variants coded by the Mal d 1.01 (on linkage group 13), -1.02, -1.06B, -1.06C genes (all on linkage group 16), nor by the Mal d 1.05 gene (on linkage group 6).
  
  
  CONCLUSIONS
  Protein variant compositions of Mal d 1.04 and -1.06A and, in case of Mal d 1.06A, allele doses are associated with the differences in allergenicity among fourteen apple cultivars. This information indicates the involvement of qualitative as well as quantitative factors in allergenicity and warrants further research in the relative importance of quantitative and qualitative aspects of Mal d 1 gene expression on allergenicity. Results from this study have implications for medical diagnostics, immunotherapy, clinical research and breeding schemes for new hypo-allergenic cultivars.
authors.affiliation: Department of Horticulture/Allergy Research Center, Zhejiang University, Hangzhou 310029, PR China. gaozhongshan@zju.edu.cn
authors.forename: Zhongshan
authors.initials: Z
authors.lastname: Gao
authors.forename: Eric W
authors.initials: EW
authors.lastname: van de Weg
authors.forename: Catarina I
authors.initials: CI
authors.lastname: Matos
authors.forename: Paul
authors.initials: P
authors.lastname: Arens
authors.forename: Suzanne T H P
authors.initials: ST
authors.lastname: Bolhaar
authors.forename: Andre C
authors.initials: AC
authors.lastname: Knulst
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Li
authors.forename: Karin
authors.initials: K
authors.lastname: Hoffmann-Sommergruber
authors.forename: Luud J W J
authors.initials: LJ
authors.lastname: Gilissen
mesh_terms: D000483:Alleles; D000485:Allergens / Q000235:genetics* / Q000276:immunology; D052179:Antigens, Plant; D003001:Cloning, Molecular; D018628:Gene Dosage; D005819:Genetic Markers; D014644:Genetic Variation; D006801:Humans; D007438:Introns; D027845:Malus / Q000009:adverse effects* / Q000235:genetics* / Q000276:immunology; D010940:Plant Proteins / Q000235:genetics* / Q000276:immunology; D012882:Skin Tests; D013045:Species Specificity
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D005819:Genetic Markers; C095551:MALD1 protein, Malus domestica; D010940:Plant Proteins