Familial Clustering of IGHC Deletions and Duplications: Functional and Molecular Analysis

Overview

Journal Immunogenetics

Specialties Allergy & Immunology
Genetics

Date 1993 Jan 1

PMID 8428768

Citations 5

Authors

A Bottaro

R GALLINA

A Brusco

U Cariota

C BOCCAZZI

M R Barilaro

A Plebani

A G Ugazio

A M van Leeuwen

G G deLange

Affiliations

Soon will be listed here.

Abstract

The human immunoglobulin heavy chain constant region locus (IGHC) comprises nine genes and two pseudogenes clustered in a 350 kilobase (kb) region on chromosome 14q32. Several IGHC haplotypes with single or multiple gene deletions and duplications have been characterized. The most likely mechanism accounting for these unusual haplotypes is the unequal crossing-over between homologous regions within the locus. Here we report the analysis of an unusual case of familial clustering of deletions/duplications. In the two branches of the BON family, three duplicated and two deleted haplotypes, all probably independent in origin, have been characterized. The structure of the haplotypes, one of which is described here for the first time, supports the hypothesis of homologous unequal crossing-over as the origin of recombinant haplotypes. The analysis of serological markers in a subject carrying one deleted and one duplicated haplotype allowed us the first direct inferences concerning the functions of the duplicated IGHC haplotypes.

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References

Bottaro A, GALLINA R, Demarchi M, Carbonara A . Genetic analysis of new restriction fragment length polymorphisms (RFLP) in the human IgH constant gene locus. Eur J Immunol. 1989; 19(11):2151-7. DOI: 10.1002/eji.1830191127. View

Smith C, Hammarstrom L, Henter J, de Lange G . Molecular and serologic analysis of IgG1 deficiency caused by new forms of the constant region of the Ig H chain gene deletions. J Immunol. 1989; 142(12):4514-9. View

Keyeux G, Lefranc G, Lefranc M . A multigene deletion in the human IGH constant region locus involves highly homologous hot spots of recombination. Genomics. 1989; 5(3):431-41. DOI: 10.1016/0888-7543(89)90006-2. View

Bottaro A, De Marchi M, De Lange G, BOCCAZZI C, Caldesi F, GALLINA R . New types of multiple and single gene deletions in the human IgCH locus. Immunogenetics. 1989; 29(1):44-8. DOI: 10.1007/BF02341612. View

Kawamura S, Omoto K, Ueda S . Evolutionary hypervariability in the hinge region of the immunoglobulin alpha gene. J Mol Biol. 1990; 215(2):201-6. DOI: 10.1016/S0022-2836(05)80336-5. View

Rautonen N, Sarvas H, Makela O . One allele [G2m(n)] of the human IgG2 locus is more productive than the other. Eur J Immunol. 1989; 19(5):817-22. DOI: 10.1002/eji.1830190506. View

Callard R, Turner M . Cytokines and Ig switching: evolutionary divergence between mice and humans. Immunol Today. 1990; 11(6):200-3. DOI: 10.1016/0167-5699(90)90082-k. View

Hendriks R, van Tol M, de Lange G, Schuurman R . Inheritance of a large deletion within the human immunoglobulin heavy chain constant region gene complex and immunological implications. Scand J Immunol. 1989; 29(5):535-41. DOI: 10.1111/j.1365-3083.1989.tb01156.x. View

Rautonen N, Seppala I, HALLBERG T, GRUBB R, Makela O . Determination of homozygosity or heterozygosity for the G2m(n) allotype by a monoclonal, precipitating antibody. Exp Clin Immunogenet. 1989; 6(1):31-8. View

10.

Kirsch I, Morton C, Nakahara K, Leder P . Human immunoglobulin heavy chain genes map to a region of translocations in malignant B lymphocytes. Science. 1982; 216(4543):301-3. DOI: 10.1126/science.6801764. View

11.

Engstrom P, Norhagen G, Bottaro A, Carbonara A, Lefranc G, Steinitz M . Subclass distribution of antigen-specific IgA antibodies in normal donors and individuals with homozygous C alpha 1 or C alpha 2 gene deletions. J Immunol. 1990; 145(1):109-16. View

12.

Olsson P, Hofker M, Walter M, Smith S, Hammarstrom L, Smith C . Ig H chain variable and C region genes in common variable immunodeficiency. Characterization of two new deletion haplotypes. J Immunol. 1991; 147(8):2540-6. View

13.

Lefranc M, Rabbitts T . Human immunoglobulin heavy chain A2 gene allotype determination by restriction fragment length polymorphism. Nucleic Acids Res. 1984; 12(3):1303-11. PMC: 318578. DOI: 10.1093/nar/12.3.1303. View

14.

Hisajima H, Nishida Y, Nakai S, Takahashi N, Ueda S, Honjo T . Structure of the human immunoglobulin C epsilon 2 gene, a truncated pseudogene: implications for its evolutionary origin. Proc Natl Acad Sci U S A. 1983; 80(10):2995-9. PMC: 393960. DOI: 10.1073/pnas.80.10.2995. View

15.

Hofker M, Walter M, Cox D . Complete physical map of the human immunoglobulin heavy chain constant region gene complex. Proc Natl Acad Sci U S A. 1989; 86(14):5567-71. PMC: 297663. DOI: 10.1073/pnas.86.14.5567. View

16.

Ueda S, Watanabe Y, Hayashida H, Miyata T, Matsuda F, Honjo T . Hominoid evolution based on the structures of immunoglobulin epsilon and alpha genes. Cold Spring Harb Symp Quant Biol. 1986; 51 Pt 1:429-32. DOI: 10.1101/sqb.1986.051.01.051. View

17.

Takahashi N, Ueda S, Obata M, Nikaido T, Nakai S, Honjo T . Structure of human immunoglobulin gamma genes: implications for evolution of a gene family. Cell. 1982; 29(2):671-9. DOI: 10.1016/0092-8674(82)90183-0. View

18.

Flanagan J, Rabbitts T . Arrangement of human immunoglobulin heavy chain constant region genes implies evolutionary duplication of a segment containing gamma, epsilon and alpha genes. Nature. 1982; 300(5894):709-13. DOI: 10.1038/300709a0. View

19.

Hofker M, Smith S, Nakamura Y, Teshima I, White R, Cox D . Physical mapping of probes within 14q32, a subtelomeric region showing a high recombination frequency. Genomics. 1990; 6(1):33-8. DOI: 10.1016/0888-7543(90)90445-z. View

20.

Hammarstrom L, Carbonara A, Demarchi M, Lefranc G, Lefranc M, Smith C . Generation of the antibody repertoire in individuals with multiple immunoglobulin heavy chain constant region gene deletions. Scand J Immunol. 1987; 25(2):189-94. DOI: 10.1111/j.1365-3083.1987.tb01063.x. View