Title

Chromosomal Organization of the Human Dihydrofolate Reductase Genes: Dispersion, Selective Amplification, and a Novel Form of Polymorphism

Authors

Nicholas P. Anagnou, National Heart, Lung, and Blood Institute
Stephen J. O'Brien, National Cancer Institute at FrederickFollow
Takashi Shimada, National Heart, Lung, and Blood Institute
William G. Nash, National Cancer Institute at Frederick
Mann-Jy Chen, National Heart, Lung, and Blood Institute
Arthur W. Nienhuis, National Heart, Lung, and Blood Institute

Document Type

Article

Publication Date

8-15-1984

Publication Title

Proceedings of the National Academy of Sciences of the United States of America

Keywords

Gene mapping, Methotrexate resistance, Intronless pseudogenes, Gene amplification

ISSN

1091-6490

Volume

81

Issue/No.

16

First Page

5170

Last Page

5174

Abstract

The human dihydrofolate reductase (DHFR; tetrahydrofolate dehydrogenase; 5,6,7,8-tetrahydrofolate: NADP⁺ oxidoreductase, EC 1.5.1.3) gene family includes a functional gene (hDHFR) and at least four intronless genes. Three intronless genes (hDHFR-ψ₂, hDHFR-ψ₃, and hDHFR-ψ₄) are identifiable as pseudogenes because of DNA sequence divergence from the functional gene with introns, while one intronless gene (hDHFR-ψ₁) is completely homologous to the coding sequences of the functional gene. Analysis of genomic DNA from two panels of somatic human-rodent cell hybrids with specific molecular probes provide insight into the chromosomal organization and assignment of these genes. The five genes are dispersed in that each one is found on a different chromosome. The functional gene hDHFR has been assigned to chromosome 5, and one pseudogene (hDHFR-ψ₄), to chromosome 3. In a human cell line (HeLa) that was selected for methotrexate resistance, the functional locus became amplified, while there was no amplification of the four intronless pseudogenes. hDHFR-ψ₁ was found to be present in DNA of some individuals and absent from DNA of others, consistent with a recent evolutionary origin of this gene originally suggested by its sequence identity to the coding portions of the functional gene. The presence or absence of this intronless pseudogene represents a previously unreported form of DNA polymorphism.

NSUWorks Citation

Anagnou, Nicholas P.; Stephen J. O'Brien; Takashi Shimada; William G. Nash; Mann-Jy Chen; and Arthur W. Nienhuis. 1984. "Chromosomal Organization of the Human Dihydrofolate Reductase Genes: Dispersion, Selective Amplification, and a Novel Form of Polymorphism." Proceedings of the National Academy of Sciences of the United States of America 81, (16): 5170-5174. https://nsuworks.nova.edu/cnso_bio_facarticles/246

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015