Abstract
BackgroundMal 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.ResultsFrom 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).ConclusionProtein 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.
Highlights
Mal d 1 is a major apple allergen causing food allergic symptoms of the oral allergy syndrome (OAS) in birch-pollen sensitised patients
These sequences were denoted according to the occurrence of 1) DNA polymorphisms in the coding region of the gene leading to different protein variants; 2) polymorphism in the coding region that did not affect the protein sequence, and 3) polymorphism in the intron (Table 1, 2)
In order to create a basis for a better understanding of the genetics of Mal d 1 genes and their impact on allergenicity, we have studied the allelic diversity of the intron containing genes in 10 cultivars that are often used in breeding
Summary
Mal d 1 is a major apple allergen causing food allergic symptoms of the oral allergy syndrome (OAS) in birch-pollen sensitised patients. The prevalence of apple allergic individuals mounts up to ~3% in Central and Northern Europe This type of apple allergy is caused by cross reactivity of IgE antibodies against the major and sensitizing birch pollen allergen Bet v 1 with Mal d 1, the major allergen of apple. From patients' experience it is known for a long time that the severity of allergic reactions to apple was related to the specific sensitivity of the individual, and largely depended on the apple cultivar. This cultivar dependent allergenicity has been described in literature. In The Netherlands (where birch pollen-related apple allergy is by far the most common form of apple allergy), this cultivar has recently been marketed as 'suited for individuals with mild apple allergy' in order to meet the general desire of apple allergic persons to be able to add this common fruit to their daily diet
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