A Caltech Library Service

γ Heavy Chain Disease in Man: cDNA Sequence Supports Partial Gene Deletion Model

Alexander, Alice and Steinmetz, Michael and Barritault, Denis and Frangione, Blas and Franklin, Edward C. and Hood, Leroy and Buxbaum, Joel N. (1982) γ Heavy Chain Disease in Man: cDNA Sequence Supports Partial Gene Deletion Model. Proceedings of the National Academy of Sciences of the United States of America, 79 (10). pp. 3260-3264. ISSN 0027-8424.

See Usage Policy.


Use this Persistent URL to link to this item:


Human gamma heavy chain disease (HCD) is characterized by the presence in serum of a short monoclonal Ig gamma chain unattached to light chains. Although most HCD proteins have internal deletions, in some the defect is NH2-terminal. The OMM gamma 3 HCD serum protein is of the latter type, having undergone an extensive NH2-terminal deletion with a sequence starting within the hinge. A cell line synthesizing the OMM protein has enabled us to study the biogenesis of the abnormal molecule. In vitro translation of isolated mRNA yields a protein containing a hydrophobic NH2-terminal leader sequence. In the intact cell, the precursor molecule is processed normally to yield a protein with an NH2-terminal sequence homologous to the beginning of the variable (V) region. The nucleotide sequence of cDNA prepared from the OMM mRNA encodes a 19-amino acid leader followed by the first 15 residues of the V region. An extensive internal deletion encompasses the remainder of the V and the entire CHl domain. Immediately following the short V region, there is information in the cDNA for the entire normal hinge. The primary synthetic product is thus an internally deleted molecule that undergoes postsynthetic degradation to yield the NH2-terminally deleted serum protein. The structure of the OMM mRNA suggests that the protein abnormality results from a partial gene deletion rather than defective splicing.

Item Type:Article
Related URLs:
URLURL TypeDescription
Hood, Leroy0000-0001-7158-3678
Additional Information:Copyright © 1982 by the National Academy of Sciences. Contributed by Edward C. Franklin, February 25, 1982. J.N.B. gratefully acknowledges the social and intellectual hospitality of L.H.'s colleagues in the Divisions of Biology and Chemistry at the California Institute of Technology during his sabbatical stay, without which the construction and cloning of the recombinant plasmids would not have been possible. The authors also acknowledge the technical expertise of Donald Hauser and the secretarial proficiency of Randi Klein. The studies were supported by Veterans Administration research funds and National Institutes of Health Grant AM01431. D.B. was a Fogarty International Fellow, M.S was a Fellow of the Deutsche Forschungsgemeinschaft, and J.N.B. was a Scholar in Cancer Research of the American Cancer Society. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Issue or Number:10
Record Number:CaltechAUTHORS:ALEpnas82
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:6605
Deposited By: Archive Administrator
Deposited On:14 Dec 2006
Last Modified:03 Mar 2020 13:01

Repository Staff Only: item control page