An international research team, including scientists from the Research Institute of the McGill University Health Centre (RI MUHC), has identified a new disease related to an inability to process vitamin B12. The discovery is important because it could help doctors diagnose the disease and, eventually, could lead to prevention or treatment. The discovery, published today in The American Journal of Human Genetics, illustrates the complex and relatively new realm of medical discovery where researchers peer into the genetic make-up of patients to discern what went wrong to cause a disease.
“Our colleagues at the University of Colorado, who led this study, informed us of a 9-year-old called Max, who was a patient at their Anschutz Medical Campus in Aurora in the US,” says Dr. David Rosenblatt, one of the study’s co-authors and a medical genetics and genomics scientist at the RI MUHC.
Max was born with symptoms that resembled a rare genetic vitamin B12 problem called cobalamin C deficiency, or cblC for short, which can cause serious health problems such as developmental delay, epilepsy, anemia, stroke, psychosis and dementia. Max’s story can be read here: www.maxwatson.org, and on Facebook: www.facebook.com/maxwatsontrust.
But Max’s symptoms seemed too severe even for cblC, and the doctors’ suspicions were confirmed when genetic testing revealed that Max did not have the mutation for that disease. “Once all our data was pooled, we were aware of 16 other individuals around the world that matched Max’s profile,” says Dr. Rosenblatt, who is also holder of the Dodd Q. Chu and Family Chair in Medical Genetics in the Department of Human Genetics at McGill University.
With the consent of Max’s parents, who cooperated with the study knowing that the results likely would not help their son but might help future patients, a research team led by University of Colorado geneticist Tamim Shaikh, PhD, used next generation genetic sequencing to delve into Max’s DNA. His genes were compared to those of other patients who did not fit the cobalamin C model. All of the patients carried mutations that hadn’t been identified before. The problem was due to flaws in a gene designed to control the workings of an enzyme that, in turn, helps the body metabolize B12.
The researchers were finally able to give a name to Max’s disease – cobalamin X, or cblX – so named because it only occurs on the X chromosome and therefore only affects males. “This study highlights the growing importance of advances in genomic technology that allows the sequencing of even fragments of the human genome to detect the underlying genetic causes of disease,” said Shaikh, who is the senior author of the study and an Associate Professor in the Department of Pediatrics at the University of Colorado.
“This discovery will lead to the correct diagnosis of this serious genetic disorder and will change the way that genetic counseling is given in these families because we now know it is x-linked,” says Dr. Rosenblatt. “It also helps explain how vitamin B 12 functions in the body, even for those without the disorder.” The next step is to determine how mutations in the gene lead to the symptoms seen in patients with cblX in hopes of better understanding the disease and – some day – being able to head it off or treat it.
Vitamin B12, also known as cobalamin, is essential for human health because it helps the body convert food into fuel. It is also vital to the healthy functioning of the human nervous system and red blood cell synthesis. Unable to produce the vitamin itself, the human body has to obtain it from animal-based foods such as milk products, eggs, red meat, chicken, fish, and shellfish – or vitamin supplements. Vitamin B12 is not found in vegetables.
Montreal Scientists develop a novel approach for scanning the entire genome
Recent technological developments in genomics have revealed a large number of genetic influences on common complex diseases, such as diabetes, asthma, cancer or schizophrenia. However, discovering a genetic variant predisposing to a disease is only a first step. To apply this knowledge towards prevention or cure, including tailoring treatment to the patient’s genetic profile –also known as personalized medicine – we need to know how this genetic variant affects health.
In a study published on July 31 in Nature Communications, Dr. Constantin Polychronakos from the Research Institute of the McGill University Health Centre (RI-MUHC), and collaborators from McGill University and The University of Texas, propose a novel approach for scanning the entire genome that will help us understand the effect of genes on human traits.
“This completely new methodology really opens up different ways of understanding how the genome affects the biology of the human body”, says Dr. Polychronakos, corresponding author of the study and Director of the Endocrine Genetics Laboratory at the Montreal Children’s Hospital and Professor in the Departments of Pediatrics and Human Genetics at McGill University.
DNA is the blueprint according to which our body is constructed and functions. Cells “read” this blueprint by transcribing the information into RNA, which is then used as a template to construct proteins – the body’s building blocks. Genes are scanned based on the association of their RNA with ribosomes – particles in which protein synthesis takes place.
“Until now, researchers have been focusing on the effects of disease-associated genomic variants on DNA-to-RNA transcription, instead of the challenging question of effects on RNA-to-protein translation,” says Dr. Polychronakos. “Thanks to this methodology, we can now better understand the effect of genetic variants on translation of RNA to protein – a powerful way of developing biomarkers for personalized medicine and new therapies.”
About this study:
Supported by the McGill University and Genome Québec Innovation Centre, the research team applied this method to a diabetes gene and discovered that at least one of the 50 genetic loci that confer risk to type-1 diabetes shows an effect on the human body by altering RNA translation to protein.
This paper is one of six that were chosen, from approximately 4000, for presentation at the plenary session of the 2012 conference of the American Society of Human Genetics.
This work was funded by Genome Canada, Génome Québec (GRiD project) and the DP3 program of the USA National Institutes of Health (NIDDK).
Click here to access the online study.
(Photo: Jaesung Kim, Alison Brebner, Moria Belanger, Peg Illson, Lena Dolman, Tracy Wang, Kush Prithipaul, Wayne Mah, Francis Petrella)
Message from Moria Belanger:
I would like to thank everyone who came out to skate, cheer, and donate on Saturday for the Free Skate/Shootout to support CanSupport. It was immensely successful and over $300 were raised! Special thanks to Francis for being our goalie and for booking the ice time, as well as to everyone who brought extra skates and helmets for people to use. I had a great time and I hope that everyone else did too! Congratulations on the trophy Alison! Hip hip hooray! I hope we can do this again!
The annual Department of Human Genetics Teaching Award is given to one member of the clinical faculty and one member of the research faculty to recognize their contributions in the teaching, supervision and mentorship of students.
This year’s winners were chosen from among several nominations submitted by students, residents and faculty members, and were announced at the Department meeting on March 14th and at the Graduate Student research Day on June 21st.
David Rosenblatt, MD
Patricia Tonin, PhD
Congratulations to the winners!
Please keep your ideas in mind for next year’s award nominees.
The Faculty Awards Committee:
Congratulations to the Winners of our Research Day Prizes:
Xiaoyang Liu – 1st prize, oral presentation
Jaeseung Kim – 1st prize, poster presentation
Juan Pablo Lopez – 2nd prize, oral presentation
Lena Dolman – 2nd prize, poster presentation
Gregory Boivin – 3rd prize, oral presentation
Jeremy Saban – 3rd prize, poster presentation
It is our pleasure to announce that Bartha Maria Knoppers, Director of the Centre of Genomics & Policy and Professor in the Department of Human genetics received the Order of Québec on June 7th, 2012 in Québec City. Please see her profile here.
David L. Rimoin, MD, PhD
The American College of Medical Genetics and Genomics (ACMG) Mourns the Loss of Founding President and Genetics Pioneer David L. Rimoin, MD, PhD
After a career that spanned nearly half a century, Dr. David L. Rimoin, founding president of ACMG and in many ways the founder of one of the most fast- paced specialties in modern clinical medicine, passed away on Sunday May 27, 2012 in Los Angeles of pancreatic cancer, which had only been diagnosed a few days before.
Dr. Rimoin was a giant in the field of medical genetics. He leaves not only an enduring legacy but also a void in the hearts of the many who loved him, including his beloved wife Ann of 32 years and their three cherished children, Anne, Michael and Lauren.
Clarke Fraser was inducted to the Canadian Medical Hall of Fame in 2012 http://www.cdnmedhall.org/list-name?year=2012
If you haven’t heard it already, Dr. Fraser was interviewed by CBC radio. The podcast can be heard here (fast forward to about 19 minutes 30 seconds) http://podcast.cbc.ca/w6/worldatsix.mp3
On April 24, during a ceremony at the Montreal Children’s Hospital, Mary Argent-Katwala, Director of Research at the Canadian Cancer Society Research Institute, presented the William E. Rawls Prize to Dr Nada Jabado, researcher at the Montreal Children’s Hospital of the McGill University Health Centre (MUHC) and Associate Professor of Pediatrics at McGill University.
The Canadian Cancer Society wants to recognize “Dr Nada Jabado’s remarkable contribution to our understanding of brain cancers in children in the last decade,” Mary Argent-Katwala said at the award ceremony.
At the Montreal Children’s Hospital, Dr Jabado diagnoses fatal tumours. Brain cancers are the leading cause of cancer-related deaths among children because existing treatments are often ineffective. A caring doctor, Dr Jabado focuses on research to one day give hope to the children she treats. “What I am hopeful and proud of is that my work might one day help cure these cancers,” the researcher said.
Innovative in her research, Dr Jabado established a multidisciplinary team composed of pediatric oncologists, bioinformaticians, pathologists and basic scientists. She then equipped the laboratory with a database of childhood tumours, thanks to the collaboration of her peers in Canada and abroad.
To this day, her work has led to great progress in the understanding of brain cancers in children and paved the way for promising treatments. Dr Jabado’s team has most notably identified a genetic mutation present in 40% of glioblastomas, a type of brain cancer. It explains the resistance of glioblastomas to radiation and chemotherapy.
Her recent work has also been the subject of several articles, notably two that appeared in Nature magazine (January and February 2012 issues).
She also won the Maude Abbott prize which was established in 2010 by the Faculty of Medicine in order to recognize outstanding female Faculty Members who excel in Education, Research or Administration with a focus at the early career stage.