ARCHIVED - Research About - Genetics

This page has been archived.

The Canadian Institutes of Health Research (CIHR) is the Government of Canada's agency for health research. CIHR's mission is to create new scientific knowledge and to catalyze its translation into improved health, more effective health services and products, and a strengthened Canadian health-care system. Composed of 13 Institutes, CIHR provides leadership and support to more than 13,000 health researchers and trainees across Canada. Through CIHR, the Government of Canada invested approximately $244.1 million in 2008-09 in genetics-related research.

---

The Facts

• The human genome contains about 20,000–25,000 genes.

• Genes contain instructions for how to make the proteins that carry out all of a cell's functions, such as facilitating chemical reactions, controlling growth and transporting substances through the body.

• Canadian scientists have been leaders in the study of human genetic diseases for the last 40 years and have participated in the identification of many important disease genes, including those for cystic fibrosis, muscular dystrophy, Alzheimer's disease, breast cancer, inherited forms of blindness and many types of congenital malformations.

• Six years after the completion of the Human Genome Project, scientists have crossed off another major item on the genetics to-do list: decoding the genome of the cow. The project involved scientists from 25 countries, including Canada.*

• Hutchinson-Gilford Progeria Syndrome, a rare genetic disease that causes premature aging, usually claims the lives of those who have it by age 13. Southern Alberta's Ashley Hegi defied the odds. She lived until April, one month short of her 18th birthday and three weeks before high school graduation.**

Sources: * New York Times, April 23, 2009. In the Genes of a Hereford, the Essence of Cow;
** CBC News, April 23, 2009, Alberta teen dies of premature aging disease.

Finding Solutions

How hereditary diseases can take hold

In the December 2008 issue of Nature Genetics, Dr. Eric Shoubridge of McGill University identified how genes can mutate as they move from mother to offspring, allowing hereditary diseases to take hold. The findings, based on mouse models, could help shed light on how stroke, epilepsy, diabetes, deafness and blindness get passed on.

Researchers identify mental retardation genes

CIHR-funded Dr. Jacques Michaud and his colleagues at Sainte-Justine Hospital in Montreal have successfully identified genes associated with mental retardation. In findings published in the New England Journal of Medicine, Dr. Michaud reported that a small but significant fraction of mentally retarded patients have genetic defects in a gene for the protein SYNGAP1, found in synapses – the specialized sites of communication between neurons. Dr. Michaud's team has also found mutations in at least 12% of the cohort of individuals they are studying. Identification of the genetic causes of mental retardation helps affected families cope with the disorder and provides the first step in developing effective treatments.

Grad student finds key to B12 uptake

Canadian researchers participating in an international effort to trace the source of a rare genetic disorder have identified a gene essential for the uptake of vitamin B12 in human cells. The research, funded in part by CIHR, involved collaboration with German, Swiss and French researchers trying to find the cause of cbIF combined homocystinuria and methylmalonic aciduria (cblF-Hcy-MMA). The disease robs people of the ability to metabolize vitamin B12, vital in making red blood cells and maintaining the nervous system. Isabelle R. Miousse, a graduate student working in the lab of McGill University's Dr. David Rosenblatt, confirmed that a gene on chromosome 6 could fix the cellular flaw in cbIF patients. The results were published in Nature Genetics in February.

Protein plays a leading role in learning

A team led by Dr. Roderick McInnes, Scientific Director of CIHR's Institute of Genetics, and Dr. Michael Salter, Head of Neurosciences and Mental Health at the University of Toronto, has found that a protein called Neto1 is critical for memory and learning in mice. Mice genetically engineered to be deficient in Neto1 show a dramatic decrease in learning and in the way their synapses – specialized sites of communication between neurons – adapt to brain activity. After giving the mice a drug being tested in patients with Alzheimer's disease, learning and memory were restored to normal. "It's part of a paradigm shift in neuroscience," said Dr. McInnes, a senior scientist at Toronto's SickKids Hospital. "Neurologists and neuroscientists have always tended to think that if the brain is abnormal at birth, nothing can be done to improve intellectual function." Their findings were published in PLoS Biology in February.

The Researchers

Dr. Ruth McPherson – The Genes of Heart Disease

One patient stands out in Dr. Ruth McPherson's mind. In his early 40s, he's athletic, fit and a non-smoker. He's also had a heart attack and two coronary artery stents.

"Based on the traditional risk factors there's no way he should have coronary heart disease," says Dr. McPherson, who leads the Ottawa Heart Institute's lipid clinic at the University of Ottawa.

However, this patient also has a father who experienced a heart attack in his 40s. In fact, about one in six Canadians who have early coronary disease don't have traditional risk factors, such as smoking, diabetes or high cholesterol levels.

It's these facts that inspired Dr. McPherson, also a molecular biologist, to explore the role genetics plays in cardiovascular disease. Her CIHR-supported research has put her at the forefront of the global search for ways to use genetic information to design new heart-health screening and treatment tools.

In 2004, her lab partnered with San Francisco-based Perlegen Sciences to conduct one of the first Genome-Wide Association Studies (GWAS) to search for heart disease-related genes. A GWAS uses high-throughput robotic molecular analysis that can analyze tens of thousands of genes combined with statistical techniques to identify regions of DNA linked to particular clinical characteristics.

The results were like an expensive Christmas present you don't know what to do with – Dr. McPherson's team discovered the strongest novel genetic link to heart disease, but with a bizarre twist: it was in a region of DNA that didn't code for a protein.

"At first we weren't very excited," recalls Dr. McPherson. "No one was expecting this result."

But after confirming the finding in more than 22,000 people, Dr. McPherson's group knew they'd hit genetic gold. The results show that an individual with two copies of this particular DNA sequence has double the chance of early heart disease as does someone without any copies. This is regardless of all other heart disease risk factors.

"That means that for two people with exactly the same other risk factors, this common genetic variant makes one person twice as likely to end up having coronary bypass surgery before the age of 55," says Dr. McPherson.

Now, she says, there's a global race to identify the molecular mechanisms at work. One possibility is that this gene sequence regulates the proliferation of cells, such as those that contribute to atherosclerosis, ultimately causing cardiovascular disease.

"For scientists this is what's the most exciting," says Dr. McPherson. "This may indicate a novel biological pathway. And this is key to understanding, and thus one day preventing and treating cardiovascular disease, both for those with traditional risk factors and those without."

For More Information

CIHR's Institute of Genetics (CIHR-IG) has identified six themes as research priorities for Canada: integrating the physical and applied sciences into health research; proteomics and bioinformatics; genomic medicine; population genetics, genetic epidemiology and complex diseases; health services for genetic diseases; and genetics and ethical, legal and social issues. To learn more about these priorities and other CIHR-IG activities, please visit the Institute's website.

For more information, go to ARCHIVED - Your Health Research Dollars at Work.