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Evolution and Organization of the Fibrinogen Locus on Chromosome 4: Gene Duplication Accompanied by Transposition and Inversion

Kant, Jeffrey A. and Fornace, Albert J., Jr. and Saxe, Debra and Simon, Melvin I. and McBride, O. Wesley and Crabtree, Gerald R. (1985) Evolution and Organization of the Fibrinogen Locus on Chromosome 4: Gene Duplication Accompanied by Transposition and Inversion. Proceedings of the National Academy of Sciences of the United States of America, 82 (8). pp. 2344-2348. ISSN 0027-8424. PMCID PMC397554. doi:10.1073/pnas.82.8.2344.

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Human fibrinogen cDNA probes for the alpha-, beta-, and gamma-polypeptide chains have been used to isolate the corresponding genes from human genomic libraries. There is a single copy of each gene. Restriction endonuclease analysis of isolated genomic clones and human genomic DNA indicates that the human alpha-, beta-, and gamma-fibrinogen genes are closely linked in a 50-kilobase region of a single human chromosome: the alpha-gene in the middle flanked by the beta-gene on one side and the gamma-gene on the other. The alpha- and gamma-chain genes are oriented in tandem and transcribed toward the beta-chain gene. The beta-chain gene is transcribed from the opposite DNA strand toward the gamma- and alpha-chain genes. The three genes have been localized to the distal third of the long arm of chromosome 4, bands q23-q32, by in situ hybridization with fibrinogen cDNAs and by examination of DNA from multiple rodent-human somatic cell hybrids. Alternative explanations for the present arrangement of the three fibrinogen genes involve either a three-step mechanism with inversion of the alpha /gamma-region or a two-step mechanism involving remote transposition and inversion. The second more simple mechanism has a precedent in the origin of repeated regions of the fibrinogen and immunoglobulin genes.

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Additional Information:© 1985 by the National Academy of Sciences. Communicated by K. M. Brinkhous, December 20, 1984. These studies were supported in part by Grant HL/GM 33942-01 from the National Institutes of Health. 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.
Funding AgencyGrant Number
NIHGM 33942-01
Subject Keywords:multigene families, gene evolution, somatic cell hybrids,in situ hybridization
Issue or Number:8
PubMed Central ID:PMC397554
Record Number:CaltechAUTHORS:KANpnas85
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:8730
Deposited By: Archive Administrator
Deposited On:11 Sep 2007
Last Modified:08 Nov 2021 20:52

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