Biology Faculty Articles

Title

Molecular Evolution of ets Genes from Avians to Mammals and Their Cytogenetic Localization to Regions Involved in Leukemia

Document Type

Article

Publication Date

1986

Publication Title

Gene Amplification and Analysis

ISSN

0275-2778

Volume

4

First Page

207

Last Page

238

Abstract

The mammalian homologues of the ets-region from the transforming gene of avian erythroblastosis virus, E26, consists of two distinct domains located on different chromosomes. Using somatic cell hybrid panels, the mammalian homolog of the 5' v-ets-domain (ets-1) was mapped to chromosome 11 in man, to chromosome 9 in mouse, and to chromosome D1 in cat. The mammalian homolog of the 3' v-ets domain (ets-2) was similarly mapped to human chromosome 21, to mouse chromosome 16, and to feline chromosome C2. To better define the human proto-ets domains, the genomic DNA was molecularly cloned and sequences analyzed. The ets-related sequences of human DNA on chromosomes 11 and 21 were found to be discontiguous, unlike that of the chicken and avian E26 virus genome, except for a small overlap region. We conclude that the ets sequence shared by the virus, the chicken and man is likely to contain at least two dissociable functional domains, identifiable as ets-1 and ets-2. The human ets-1 locus is transcriptionally active and encodes a single mRNA of 6.8 kb, while the second locus, human ets-2 encodes three mRNAs of 4.7, 3.2 and 2.7 kb. By contrast, the chicken homolog, having a contiguous ets-1 and ets-2 sequence, is primarily expressed in normal chicken cells as a single 7.5 kb mRNA. Because chromosome translocations have been associated with different human disorders, we have used our human probes with two panels of rodent-human cell hybrids to study specific translocations occurring in acute myeloid leukemias (AML). The human ets-1 gene was found to translocate from chromosome 11 to 4 in t(4;11)(q21;q23) and the human ets-2 gene was found to translocate from chromosome 21 to 8 in t(8;21)(q22;q22). Both translocations were found associated with the altered expression of ets.

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015

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