Abstract
The present study investigates the molecular basis of the G3m polymorphism expressed by the heavy constant domains of human immunoglobulins gamma 3 chains. By using a new protocol allowing the specific cloning of IGHG3 genes, a total of 51 full-length IGHG3 genomic sequences (about 2 kb) isolated from African, Siberian, West Asian and European population samples were sequenced. IGHG3 sequences were assigned precise G3m haplotypes on the basis of specific associations between G3m allotypes and IGHG3 RFLPs. Specific DNA substitutions involved in the expression of G3m(5), G3m(6), G3m(15), G3m(16), G3m(21), G3m(24) and G3m(28) allotypes were then deduced, elucidating almost completely the determination of the G3m polymorphism at the DNA level. The molecular evolution of G3m haplotypes was investigated by a maximum likelihood phylogeny of IGHG3 sequences. Sequence clusters are shown to be G3m haplotype-specific, corroborating the Gm molecular model deduced from serology, and showing that populations differentiation is much more recent than G3m haplotypes differentiation. The widely distributed G3m5,10,11,13,14 haplotype is likely to be ancestral to the other G3m haplotypes presently found at high frequencies in different continental areas.
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Acknowledgements
This work was supported by FNRS grant 32-39720.93 to A Sanchez-Mazas, Switzerland. The expeditions in Siberia were financially supported by the rasnoselkup's Administration. We also thank Pr A Langaney for stimulating the present work, Dr L Excoffier for involvement in the study of Mandenka, Pr G Lefranc for revising the manuscript, Dr V Wiebe for long assistance in the study of Selkup populations, and anonymous reviewers for their helpful comments. Once again, we acknowledge the local populations (Mandenka and Selkup) and the other typed individuals for their consented collaboration.
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Dard, P., Lefranc, MP., Osipova, L. et al. DNA sequence variability of IGHG3 alleles associated to the main G3m haplotypes in human populations. Eur J Hum Genet 9, 765–772 (2001). https://doi.org/10.1038/sj.ejhg.5200700
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DOI: https://doi.org/10.1038/sj.ejhg.5200700
Keywords
- IgG immunoglobulins
- Gm allotypes
- IGHG3
- DNA polymorphism
- human genetic diversity
- evolution
- phylogeny
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