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1、免疫球蛋白基因组第1页，共19页，编辑于2022年，星期五ImmunoglobulinStructuresHeavy chain and light chain(and)Constant regionClass:IgA,IgD,IgE,IgG and IgMVariable region Antigen binding site第2页，共19页，编辑于2022年，星期五Generation of diversitiesAIDN-Regions第3页，共19页，编辑于2022年，星期五Part 1 Immunoglobulin germline gene repertoire study第4页，
2、共19页，编辑于2022年，星期五IGHV gene repertoireHighly 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，共19页，编辑于2022年，星期五IGKV gene repertoire
3、analysisCompilation of Database Compilation of 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.Unreporte
4、d IGKV allelesUnreported IGKV alleles IGKV alleles with low number of unmutated sequences were IGKV alleles with low number of unmutated sequences were collectedcollected Multiple alignmentMultiple alignment Shared mismatchesShared mismatches Sequencing from genomic DNASequencing from genomic DNA第6页
5、，共19页，编辑于2022年，星期五Junction analysis of IGK genes435 low mutation sequences(3 IGKV mutations)were realigned to determine IGKJ genes using V-QUESTVJ gene useageN-Region第7页，共19页，编辑于2022年，星期五第8页，共19页，编辑于2022年，星期五Results5 reported genes may be the result of sequencing 5 reported genes may be the result o
6、f sequencing errorserrorsIGKV1D-13*01 and IGKV1-37*01 may be IGKV1D-13*01 and IGKV1-37*01 may be functional in some individualsfunctional in some individualsUnreported polymorphisms:IGKV1-16*02 and Unreported polymorphisms:IGKV1-16*02 and IGKV2-30*02.IGKV2-30*02.The existing IGKV repertoire is relat
7、ively complete and The existing IGKV repertoire is relatively complete and accurateaccurate第9页，共19页，编辑于2022年，星期五第10页，共19页，编辑于2022年，星期五ConclusionsNot only is there little diversity in the germline genes of Not only is there little diversity in the germline genes of the kappa locus,but little junction
8、al diversity is 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 The immunoglobulin gene repertoire can therefore be characterised as having extrao
9、rdinary diversity in be characterised as having extraordinary diversity in the heavy chain,and limited diversity in the light the heavy chain,and limited diversity in the light chain.chain.第11页，共19页，编辑于2022年，星期五Part 2Sequencing immunoglobulin genes from allergic and parasitised individuals第12页，共19页，
10、编辑于2022年，星期五IgE and AllergyNatural function of IgE Parasite infectionsIgE and Allergic diseaseAntigen selection in IgEThe relationship between IgE and IgG4第13页，共19页，编辑于2022年，星期五Understanding IgE mutations in PNGPNG IgE vs PNG IgGOther Factors Exposure to pathogensExposure to pathogens AgeAge第14页，共19
11、页，编辑于2022年，星期五Two QuestionsIs there a higher level of mutation in antibodies of PNG villagers,compared to Australia urban individuals?Are higher numbers of mutations seen in older individuals?第15页，共19页，编辑于2022年，星期五第16页，共19页，编辑于2022年，星期五Sample NameIgEIgGNo.of IgAverage Mutation No.No.of IgAverage Mut
12、ation 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，共19页，编辑于2022年，星期五AcknowledgementsAndrew Collins William SewellKatherine JacksonViveka SinghEllie PrattBruno GaetaJeanette VillanuevaJames LazenbyChristine WhittallAngela Higgins第18页，共19页，编辑于2022年，星期五Thank you!第19页，共19页，编辑于2022年，星期五