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1、免疫球蛋白基因组第1页，此课件共19页哦ImmunoglobulinStructuresHeavy chain and light chain(and)Constant regionClass:IgA,IgD,IgE,IgG and IgMVariable region Antigen binding site第2页，此课件共19页哦Generation of diversitiesAIDN-Regions第3页，此课件共19页哦Part 1 Immunoglobulin germline gene repertoire study第4页，此课件共19页哦IGHV gene repertoir
2、eHighly polymorphic226 reported genes and allelic variants104 was reported in error 12 putative new polymorphisms,3 have been sequencedConclusion:The existing IGHV gene repertoire is full of incorrectly reported sequences.第5页，此课件共19页哦IGKV gene repertoire analysisCompilation of Database Compilation o
3、f Database 1863 rearranged IGKV sequences from the EMBL1863 rearranged IGKV sequences from the EMBL 66 germline genes from the IMGT66 germline genes from the IMGTAlignments using Smith-Waterman algorithm.Alignments using Smith-Waterman algorithm.Unreported IGKV allelesUnreported IGKV alleles IGKV al
4、leles with low number of unmutated sequences were collectedIGKV alleles with low number of unmutated sequences were collected Multiple alignmentMultiple alignment Shared mismatchesShared mismatches Sequencing from genomic DNASequencing from genomic DNA第6页，此课件共19页哦Junction analysis of IGK genes435 lo
5、w mutation sequences(3 IGKV mutations)were realigned to determine IGKJ genes using V-QUESTVJ gene useageN-Region第7页，此课件共19页哦第8页，此课件共19页哦Results5 reported genes may be the result of sequencing errorsIGKV1D-13*01 and IGKV1-37*01 may be functional in some individualsUnreported polymorphisms:IGKV1-16*02
6、 and IGKV2-30*02.The existing IGKV repertoire is relatively complete and The existing IGKV repertoire is relatively complete and accurateaccurate第9页，此课件共19页哦第10页，此课件共19页哦ConclusionsNot only is there little diversity in the germline genes Not only is there little diversity in the germline genes of th
7、e kappa locus,but little junctional diversity is of the kappa locus,but little junctional diversity is generated during the process of gene rearrangement.generated during the process of gene rearrangement.The immunoglobulin gene repertoire can therefore be characterised as having extraordinary diver
8、sity in the heavy chain,and limited diversity in the light chain.第11页，此课件共19页哦Part 2Sequencing immunoglobulin genes from allergic and parasitised individuals第12页，此课件共19页哦IgE and AllergyNatural function of IgE Parasite infectionsIgE and Allergic diseaseAntigen selection in IgEThe relationship between
9、 IgE and IgG4第13页，此课件共19页哦Understanding IgE mutations in PNGPNG IgE vs PNG IgGOther Factors Exposure to pathogensExposure to pathogens AgeAge第14页，此课件共19页哦Two QuestionsIs there a higher level of mutation in antibodies of PNG villagers,compared to Australia urban individuals?Are higher numbers of muta
10、tions seen in older individuals?第15页，此课件共19页哦第16页，此课件共19页哦Sample NameIgEIgGNo.of IgAverage Mutation No.No.of IgAverage Mutation No.Australia1812.85217.6A000001019.5A0021102418.8A006910.61815.1A007815.600PNG2017.76619.8P002(Old)423620.3P008(Old)1417.11423.1P011(young)211.54618.8第17页，此课件共19页哦AcknowledgementsAndrew Collins William SewellKatherine JacksonViveka SinghEllie PrattBruno GaetaJeanette VillanuevaJames LazenbyChristine WhittallAngela Higgins第18页，此课件共19页哦Thank you!第19页，此课件共19页哦