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Opinion

Split Immunoglobulin Genes and Human Heavy Chain Deletion-Mutants¹

From the Irvington House Institute, Departments of Medicine and Pathology, New York University Medical Center, 550 First Avenue, New York, New York 10016

Abstract

In 1965, the "two gene-one polypeptide" theory for the synthesis of antibody chains was first proposed (1). Since then, amino acid sequence studies and genetic analyses of the variable (V)² and constant (C) regions of light (L) and heavy (H) chains have been consistent with this hypothesis (2). A direct demonstration of the existence of separate genetic units was achieved in 1977 (3), when it was shown that the DNA segments (exon DNA) coding for V and C regions of mouse L chains ( type) are separated from one another by a large DNA segment (intron or intervening sequence or IVS) that is missing from the mRNA that serves as the template for the L chain. In addition, in DNA derived from embryonic cells, the V gene is shorter than expected (4, 5), ending at the codon specifying position 98 instead of 112 commonly accepted at the VC joining region.

Footnotes

¹ This work was supported by United States Public Health Service Research Grants AM 01431 and AM 02594.

² Abbreviations used in this paper: V, variable; C, constant; L, light; H, heavy; IVS, intron or intervening sequence; HCD, heavy chain disease.