New consortium to investigate mechanisms of developmental disorders

A new consortium is to exploit ongoing research to identify genes that are essential for mouse development in order to investigate the origins of developmental diseases and birth defects in humans.

The Deciphering the Mechanisms of Developmental Disorders (DMDD) programme will make use of the Wellcome Trust Sanger Institute's Mouse Genetics Programme, which is creating mouse strains with targeted disruptions in each of the 20,000 genes in the mouse genome as part of the International Knockout Mouse Consortium. Research has shown that around one-third of genes are essential for the normal development of the mouse and without them, the mouse either does not survive beyond the embryonic stage or dies as a newborn.

DMDD will use high-resolution 3D imaging of embryos to identify the developmental abnormalities that occur after the removal of individual genes and to generate detailed descriptions of the physical changes that result. The database produced by this project will be freely available for the wider research community in order to catalyse new discoveries in developmental biology.

The project will interact with and be informed by existing research programmes such as the Deciphering Developmental Diseases consortia, which helps doctors to understand the genetic mutations that cause birth defects and developmental disorders in humans. DMDD will enable genes identified from these studies to be investigated in mice, to uncover the molecular mechanisms that lead to such developmental defects.

Around a quarter of all of our genes are essential for the development of babies in the womb. Around one in 40 infants in Europe are born with inherited or spontaneous defects in one or more of these genes, causing birth defects. These defects can affect organs such as the heart, lungs or kidneys, the positioning or growth of bones, or the formation of the spine and brain. Some defects are so severe that they result in miscarriage or stillbirth.

Identifying how defective genes cause these abnormalities by investigating the underlying molecular mechanisms will lead to the invention of better genetic screening strategies and diagnosis, and could potentially result in new therapies to alleviate or prevent developmental diseases.

The five-year study, which is due to begin in spring 2013, is being funded by a £5 million Strategic Award from the Wellcome Trust and will be led by researchers at the MRC National Institute for Medical Research. The consortium is described this week in an editorial published online in the journal 'Disease Models and Mechanisms'.