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Finding Phenotypes

Genes shared across species that produce different phenotypes—deafness in humans and directional growth in plants—may reveal new models of disease.


CANCER OR MORE BOYS: A mutated form of the human gene for breast cancer is also responsible for producing more male progeny in C. elegans worms, pictured here.
PHOTO RESEARCHERS, INC., SINCLAIR STAMMERS

EDITOR’S CHOICE IN GENETICS

The paper

K.L. McGary et al., “Systematic discovery of nonobvious human disease models through orthologous phenotypes,” PNAS, 107:6544-49, 2010.

The finding

Edward Marcotte, of the University of Texas at Austin, was always interested in how the same groups of conserved genes could be linked to such different traits in different organisms. For example, mutated forms of the BRCA1 gene, which are associated with breast cancer in humans, are also responsible for a higher frequency of male progeny in C. elegans. Searching for common gene networks or systems across very different species, Marcotte and his colleagues uncovered surprising relationships—coined phenologs—that could help locate new disease-related genes or be used to screen therapeutic compounds.

The common genes

Using a database of gene-phenotype relationships, as well as raw literature searches, the group found 3,755 phenologs between human and mouse gene mutations, 154 between human and yeast, and 9 between human and worm, many of which were previously discovered disease models, helping validate the approach.

The deaf plant

The search uncovered several new and unusual models. In humans, a gene mutation that causes deafness was also involved in detecting gravity and directional growth in plants. Though they give rise to different phenotypes, the genes are likely part of an “ancient machine,” said Marcotte. Studying the interacting genes and proteins in the plant could reveal novel genes associated with the human disease.

The implications

Published 2 years ago, Marcotte’s study is proving to be truly “reflective of a trend in genomic analysis in recent years” says Elissa Chesler of the Jackson Laboratory in an e-mail.

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TAGGED: GENETICS


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