Open Access Research article

Assessment of allelic diversity in intron-containing Mal d 1 genes and their association to apple allergenicity

Zhongshan Gao123, Eric W van de Weg23*, Catarina I Matos2, Paul Arens3, Suzanne THP Bolhaar4, Andre C Knulst4, Yinghui Li35, Karin Hoffmann-Sommergruber6 and Luud JWJ Gilissen23

Author Affiliations

1 Department of Horticulture/Allergy Research Center, Zhejiang University, Hangzhou 310029, PR China

2 Allergy Consortium Wageningen, Wageningen University and Research Centre, P.O. Box 16, 6700AA, Wageningen, the Netherlands

3 Plant Research International, Wageningen University and Research Centre, P.O. Box 16, 6700AA, Wageningen, the Netherlands

4 Department of Dermatology/Allergology, University Medical Center Utrecht, P.O. Box 85500, 3508GA Utrecht, the Netherlands

5 The National Key Facility for Crop Gene Resources and Genetic Improvement (NFCRI)/Key Lab of Germplasm & Biotechnology (MOA), Institute of Crop Science, China Academy of Agricultural Science, Beijing, 100081, PR China

6 Department of Pathophysiology, Medical University of Vienna, AKH-EBO-3Q, Währinger Gürtel 18-20, A-1090 Vienna, Austria

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BMC Plant Biology 2008, 8:116  doi:10.1186/1471-2229-8-116

Published: 13 November 2008



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.


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).


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.