Immunoglobulin heavy chain genes in humans are located on chromosome 14

Hobart, M. J.; Rabbitts, Terence H.; Goodfellow, Peter N.; Solomon, Ellen; Chambers, Scott R.; Spurr, Nigel K.; Povey, S.

doi:10.1111/j.1469-1809.1981.tb00346.x

Cited by 95 publications

(22 citation statements)

References 18 publications

(11 reference statements)

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“…For lymphoid tumours, one of the ®rst clues came from the mapping of the human immunoglobulin (Ig) heavy chain locus to the long arm of chromosome 14 (Croce et al, 1979;Hobart et al, 1981). At the time, gene mapping by chromosome in situ hybridization was restricted to multi-copy genes but we used the technique to map the human K light chain genes to chromosome 2, band p12 (Malcolm et al, 1982), using a variable region probe (which is e ectively multi-copy due to cross hybridization between di erent V genes (Bentley and Rabbitts, 1981)).…”

Section: Cloning Genes At Chromosomal Translocation Breakpointsmentioning

confidence: 99%

Chromosomal translocation master genes, mouse models and experimental therapeutics

Rabbitts

2001

Oncogene

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Molecular biologists have elucidated general principles about chromosomal translocations by cloning oncogenes or fusion genes at chromosomal translocation junctions. These genes invariably encode intracellular proteins and in acute cancers, often involve transcription and developmental regulators, which are master regulators of cell fate (e.g. LMO2 which is involved in acute leukaemia). Chromosomal translocations are usually associated with speci®c cell types. The reason for this close association is under investigation using mouse models. We are trying to emulate the cell-speci®c consequences of chromosomal translocations in mice using homologous recombination in embryonic stem cells to generate de novo chromosomal translocations or to mimic the consequence of these translocations. In addition, chromosomal translocation genes and their products are important targets for therapy. We have designed new therapeutic strategies which include antigen-speci®c recruitment of endogenous cellular pathways to a ect cellular viability and a novel structured form of antisense to ablate the function of fusion mRNAs. We will evaluate these procedures in the mouse models of chromosomal translocations and the long term aim is to perfect rapid procedures for characterizing patient-speci®c chromosomal translocations to tailor therapy to individual patients. Oncogene (2001) 20, 5763 ± 5777.

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Section: Cloning Genes At Chromosomal Translocation Breakpointsmentioning

confidence: 99%

Chromosomal translocation master genes, mouse models and experimental therapeutics

Rabbitts

2001

Oncogene

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“…A principle example of this is the translocation t(8;14)(q24;q32.1) invariably found in the human B cell tumor Burkitt's lymphoma (Manolov and Manolov 1972;Zech et al 1976). The link with the immunoglobulin H-chain locus on chromosome 14, band q32.1 (Croce et al 1979;Hobart et al 1981) and subsequently with the K light-chain locus on chromosome 2, band p12 (Malcolm et al 1982), suggested that the immunoglobulin genes might be associated with the translocation breakpoints. The cloning of the CMYC proto-oncogene associated with the IgH locus from Burkitt's lymphoma translocation breakpoint t(8;14)(q24;q32) confirmed this.…”

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confidence: 99%

LMO T-cell translocation oncogenes typify genes activated by chromosomal translocations that alter transcription and developmental processes

Rabbitts¹

1998

Genes Dev.

158

146

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“…The VH genes have been localized to chromosome 14 by somatic cell hybrids (23) and several have been cloned and sequenced. Matthyssens and Rabbitts (24) found several instances in which two Ig VHIII genes were found within a single phage, separated by 12-16 kilobases (kb) of spacer DNA (25).…”

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confidence: 99%

“…We next wanted to test for linkage between the VH polymorphic loci and the CH loci also present on chromosome 14 in humans (23). All of the informative families for VH region loci had been typed previously for CH region markers and all were informative at the latter locus for testing linkage between the two clusters.…”

mentioning

confidence: 99%

Polymorphisms of a human variable heavy chain gene show linkage with constant heavy chain genes.

Johnson¹,

Natali²,

Cann³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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In this study, restriction fragment length polymorphisms (RFLPs) were identified with an immunoglobulin variable heavy chain region (Ig VH) probe and the inheritance of the polymorphisms was analyzed in families. Linkage within the VHII gene cluster and between the VHII and Ig CH genes was investigated by lod (logarithm of odds) score analysis. In addition, the position of the VHII genes was determined in relation to another polymorphic locus-D14S1, which is tightly linked and centromeric to the CH genes. Genetic associations between genes in the CH and VH clusters were analyzed.These RFLPs represent genetically characterized VH region polymorphisms and it is hoped that they will facilitate the study of disease correlations as well as further the understanding of the genetics of the immunoglobulin heavy chain genes in humans.The immunoglobulins consist of four polypeptide chains, two heavy (H) and two light (L), each of which contains a variable (V) region-encoded amino terminus covalently attached to a constant (C) region-encoded carboxyl terminus. The V region polypeptides can be divided into functional segments categorized as framework regions (FR1-4) and hypervariable or complementarity-determining regions (CDR1-3). Each VH polypeptide is composed of sequences encoded by three different genetic elements. These are (i) V region sequences coding for amino acids 1-98, which form FR1-3 and CDR1 and CDR2; (it) diversity (D) region sequences coding for amino acids 99-103, which form CDR3; and (iil) joining (J) region sequences coding for amino acids 103-110, forming FR4 (1-3). A rearranged VH sequence can be recombined subsequently to the 5' end of any CH subclass region sequence by a process known as class switching (4), which illustrates that a single VH gene can be combined with any of the CH genes (5, 6).Antibody specificity is determined by genetic differences in the V region genes (idiotypes) (6)(7)(8)(9). This idiotypic variation has been studied extensively in mice and rabbits. As early as 1963, antigenic determinants located on V regions of rabbit IgH chains were found (10). Pedigree analysis of rabbits homozygous for two different VH region allotypes demonstrated that VH and CH region allotypes were linked, although recombinants were observed (11).Mendelian studies involving idiotypic determinants of mice have determined that the Ig CH and Ig VH loci are also linked (9, 12-15), although separated by a substantial distance (2). Mouse strains of the same allotype have identical VH gene families; however, in comparisons between inbred strains, each VH gene family is comparable in number but not in the composition of the individual VH genes (16).Utilizing molecular data, it was shown that polytnorphisms in VH coding sequences are directly responsible for two major anti-arsonate idiotypes in A/J mice (17) as well as for different responses to proteins bearing the hapten (4-hydroxy-3-nitrophenyl)acetyl (18). Furthermore, a molecular genetic study of germline variation in six inbred mouse strains demons...

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Immunoglobulin heavy chain genes in humans are located on chromosome 14

Abstract: The human immunoglobulin heavy chain gene complex has been assigned to chromosome 14 by filter hybridization of restriction digests of mouse-human somatic cell hybrids. Cloned DNA probes for both variable and constant regions were used.

Cited by 95 publications

References 18 publications

Chromosomal translocation master genes, mouse models and experimental therapeutics

Chromosomal translocation master genes, mouse models and experimental therapeutics

LMO T-cell translocation oncogenes typify genes activated by chromosomal translocations that alter transcription and developmental processes

Polymorphisms of a human variable heavy chain gene show linkage with constant heavy chain genes.

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