Important discovery for the diagnosis of genetic diseases

(Press-News.org) Contact information: Julie Langelier
julie.langelier@ircm.qc.ca
514-987-5555
Institut de recherches cliniques de Montreal
Important discovery for the diagnosis of genetic diseases IRCM researchers show the importance of the DNA architecture in controlling the activity of genes Montréal, January 16, 2014 – A study conducted by Marie Kmita's team at the IRCM, in collaboration with Josée Dostie at McGill University, shows the importance of the chromatin architecture in controlling the activity of genes, especially those required for proper embryonic development. This discovery, recently published in the scientific journal PLOS Genetics, could have a significant impact on the diagnosis of genetic diseases.

Each cell in the body contains a person's genetic information in the form of DNA molecules, wrapped around structures called nucleosomes. Together, the DNA and nucleosomes form the chromatin, which is the main component of chromosomes.

"Our work shows that the regulation of the activity of genes controlling embryonic development is linked to the three-dimensional organization of the chromatin," explains Dr. Kmita, Director of the Genetics and Development research unit at the IRCM. "In fact, this chromatin architecture, which varies according to the cell type, generates specific contacts between sequences of regulatory DNA and the genes they regulate."

To date, studying the causes of genetic diseases is mainly achieved through DNA sequencing and the analysis of gene sequences. However, the cause of such diseases could just as well be an anomaly in the DNA sequences that control the genes.

"It is now possible to identify regulatory DNA that controls a given gene," adds Dr. Kmita. "Our discovery paves the way for studying the mechanisms that control the architecture of chromatin, which should have a significant impact on identifying the causes and diagnosing genetic diseases."

The IRCM researchers' scientific breakthrough could have an impact on a large number of genetic diseases, including those associated with the Hox genes studied by Dr. Kmita, such as synpolydactyly (a congenital malformation characterized by the fusion of digits and the production of additional digits) and the hand-foot-genital syndrome (a genetic disease characterized by limb malformations and urogenital defects).

### About the research project The study was conducted in collaboration with Dr. Josée Dostie's team at Rosalind and Morris Goodman Cancer Research Centre – McGill University. The IRCM researchers who contributed to this project are Soizik Berlivet (first author), Annie Dumouchel and David Langlais. Dr. Kmita's research was funded by the Canadian Institutes of Health Research and the Canada Research Chairs Program.

For more information, please refer to the article published online by the PLOS Genetics: http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004018.

About Marie Kmita Marie Kmita obtained her PhD in cell and molecular biology from the Université de Reims in France. She is Associate IRCM Research Professor and Director of the Genetics and Development research unit. Dr. Kmita is associate research professor in the Department of Medicine (accreditation in molecular biology) at the Université de Montréal. She is also Adjunct Professor in the Department of Medicine (Division of Experimental Medicine) and the Department of Biology at McGill University. Dr. Kmita holds the Canada Research Chair in Molecular Embryology and Genetics. For more information, visit http://www.ircm.qc.ca/kmita.

About the IRCM Founded in 1967, the Institut de recherches cliniques de Montréal is currently comprised of 35 research units in various fields, namely immunity and viral infections, cardiovascular and metabolic diseases, cancer, neurobiology and development, systems biology and medicinal chemistry. It also houses four specialized research clinics, eight core facilities and three research platforms with state-of-the-art equipment. The IRCM employs 425 people and is an independent institution affiliated with the Université de Montréal. The IRCM Clinic is associated to the Centre hospitalier de l'Université de Montréal (CHUM). The IRCM also maintains a long-standing association with McGill University. The IRCM is funded by the Quebec ministry of Higher Education, Research, Science and Technology.

About the Canadian Institutes of Health Research The Canadian Institutes of Health Research (CIHR) is the Government of Canada's health research investment agency. CIHR's mission is to create new scientific knowledge and to enable its translation into improved health, more effective health services and products, and a strengthened health care system for Canadians. Composed of 13 Institutes, CIHR provides leadership and support to more than 12,600 health researchers and trainees across Canada. http://www.cihr-irsc.gc.ca