DNA sequence variability of IGHG3 alleles associated to the main G3m haplotypes in human populations

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 fr...

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Veröffentlicht in:European journal of human genetics : EJHG 2001-10, Vol.9 (10), p.765-772
Hauptverfasser: Dard, P, Lefranc, M P, Osipova, L, Sanchez-Mazas, A
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Lefranc, M P
Osipova, L
Sanchez-Mazas, A
description 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 G3m(5,10,11,13,14) haplotype is likely to be ancestral to the other G3m haplotypes presently found at high frequencies in different continental areas.
doi_str_mv 10.1038/sj.ejhg.5200700
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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; SpringerLink Journals - AutoHoldings
subjects Alleles
Allotypes
Asia, Western
Base Sequence
Cloning
Deoxyribonucleic acid
DNA
Ethnic Groups - genetics
Europe
Female
Gene Frequency
Gene polymorphism
Genes
Genetics
Haplotypes
Haplotypes - genetics
Humans
Immunoglobulin gamma-Chains - genetics
Immunoglobulins
Male
Molecular evolution
Multiple myeloma
Nucleotide sequence
Phylogeny
Polymorphism, Genetic - genetics
Polymorphism, Restriction Fragment Length
Population genetics
Population studies
Senegal
Serology
Siberia
Studies
title DNA sequence variability of IGHG3 alleles associated to the main G3m haplotypes in human populations
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