Retrotransposons as controlling elements in mammals: a screen for expression in somatic cells and cancer

Funded Activity Summary

Differences between individual mammals are generally thought to be due to differences either between their genes, or between their environments. However, in many cases genetic or environmental factors cannot account for differences between individuals. We have studied mice in which dramatic differences between genetically identical individuals are due solely to the activity of a type of transposable element (transposon). There are tens of thousands of similar elements in the genomes of all mammals. A large body of evidence demonstrates that transposons can disrupt gene expression. To prevent this from occurring, most organisms have evolved mechanisms to keep transposons silent. However, fragmentary evidence indicates that transposons are at least sometimes expressed in normal and cancer cells. We hypothesize that activity of transposons in mammals alters gene expression sufficiently to cause variation between individuals, and that altered gene expression can cause disease (particularly cancer) and some manifestations of aging. As a first step toward testing this hypothesis, it is essential to acquire more complete information on the expression of transposons in normal and diseased cells. Furthermore, if transposon expression is closely linked to the development or progression of cancer or aging, then the ability to monitor such expression could have diagnostic utility. DNA array technology is coming into wide use to compare patterns of gene expression in different types of cells. We propose to adapt this method to the study of transposon expression. We will clone examples of all known classes of mouse and human transposon, and study transposon expression in: 1. Normal mice, at intervals from the earliest phase of development to old age, and 2. Human cancers of a variety of types. These studies will provide information of fundamental significance for mammalian biology, and also have the potential to lead to improved diagnosis of disease.

Funded Activity Details

Start Date: 01-01-2001

End Date: 01-01-2003

Funding Scheme: NHMRC Project Grants

Funding Amount: $452,545.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Gene Expression

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

Aging | Cancer | Development | Epigenetics | Gene regulation | Genetic Disease | Retrotransposon

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