Also check out our latest Beaker post on our CDG research.
The three children in this study, from left to right: Oliver, Edward, and Amira-Zoe.
Children born with rare, inherited conditions known as Congenital Disorders of Glycosylation, or CDG, have mutations in one of the many enzymes the body uses to decorate its proteins and cells with sugars. Properly diagnosing a child with CDG and pinpointing the exact sugar gene that’s mutated can be a huge relief for parents—they better understand what they’re dealing with and doctors can sometimes use that information to develop a therapeutic approach. Whole-exome sequencing, an abbreviated form of whole-genome sequencing, is increasingly used as a diagnostic for CDG.
Liam
Finding the cause of Liam’s metabolic disease
Originally published February 7, 2012
Sequencing a patient’s entire genome to discover the source of his or her disease is not routine – yet. But geneticists are getting close.
A case report, published February 2 in the American Journal of Human Genetics, shows how researchers can combine a simple blood test with an “executive summary” scan of the genome to diagnose a type of severe metabolic disease. In the study, researchers at Emory University School of Medicine and Sanford-Burnham used whole-exome sequencing to find the mutations causing a glycosylation disorder affecting Liam, a boy born in 2004.
Whole-exome sequencing reads only the parts of the human genome that encode proteins, leaving the other 99 percent of the genome unread. This method is cheaper and faster than whole-genome sequencing, but is still an efficient strategy for reading the parts of the genome scientists believe are the most important for diagnosing disease. It is estimated that most disease-causing mutations (around 85 percent) are found within the regions of the genome that encode proteins, the workhorse machinery of the cell. The report illustrates how whole-exome sequencing, which was first offered commercially for clinical diagnosis in 2011, is entering medical practice. Emory Genetics Laboratory is now gearing up to start offering whole-exome sequencing as a clinical diagnostic service.
Normal cells containing green fluorescent protein (left) don't glow. In contrast, cells from a child with a glycosylation disorder (right) light up, signaling a genetic defect.
Just as Gotham City uses the Bat Signal to call for Batman’s aid, a new tool developed by Sanford-Burnham scientists should serve as the cellular equivalent for children with genetic diseases known as congenital disorders of glycosylation (CDG). In a new report appearing online June 12 in The FASEB Journal, the scientists describe how they used a green fluorescent protein originally isolated from jellyfish to identify the presence of genes—known and unknown—associated with CDG. By being able to identify exactly which genes are defective, researchers can develop therapies to correct the root causes of these diseases, rather than merely treating the symptoms.
Mason with Dr. Hudson Freeze (left) and philanthropist T. Denny Sanford, big supporter of children's health research, at Sanford-Burnham's third annual Rare Disease Day Symposium
Ten year-old Mason Barto is a sweet Pennsylvania fifth grader almost like any other. Except that he’s lived with a tracheotomy, a permanent feeding tube, and a number of other health problems since birth. Mason’s condition was inherited, but for most of his life no one could pinpoint the genetic cause of his health problems. They didn’t even have a name for it.
Then, a few months ago, Sanford-Burnham’s Dr. Hudson Freeze and his team finally discovered the genetic defect underlying Mason’s health problems and diagnosed him with what’s called a congenital disorder of glycosylation (CDG). In other words, Mason has a mutation in a gene that directs glycosylation—the process by which cells coat proteins with sugars. Lack of sugars disrupts cell growth, differentiation, and communication. There are several different types of CDG and symptoms and severity can vary widely.
While it doesn’t mean there’s an immediate cure for Mason, he is now taking a simple sugar therapy and is beginning to show early signs of improvement. The finding also gives new hope to other children living with this condition.
Liam
Sequencing a patient’s entire genome to discover the source of his or her disease is not routine – yet. But geneticists are getting close.
A case report, published February 2 in the American Journal of Human Genetics, shows how researchers can combine a simple blood test with an “executive summary” scan of the genome to diagnose a type of severe metabolic disease. In the study, researchers at Emory University School of Medicine and Sanford-Burnham used whole-exome sequencing to find the mutations causing a glycosylation disorder affecting Liam, a boy born in 2004.
Whole-exome sequencing reads only the parts of the human genome that encode proteins, leaving the other 99 percent of the genome unread. This method is cheaper and faster than whole-genome sequencing, but is still an efficient strategy for reading the parts of the genome scientists believe are the most important for diagnosing disease. It is estimated that most disease-causing mutations (around 85 percent) are found within the regions of the genome that encode proteins, the workhorse machinery of the cell. The report illustrates how whole-exome sequencing, which was first offered commercially for clinical diagnosis in 2011, is entering medical practice. Emory Genetics Laboratory is now gearing up to start offering whole-exome sequencing as a clinical diagnostic service.
Gianna Dragatto, a young patient with a rare disease called Congenital Disorders of Glycosylation
What: Third Annual Sanford-Burnham Rare Disease Day Symposium: Identifying and Treating Genetic Diseases in Children
Where: Sanford-Burnham Medical Research Institute, La Jolla, Calif., Building 12 (map)
When: February 24, 2012 – registration opens at 8:00 a.m. PT, program begins at 9:00 a.m. PT
Keynote speaker: Dr. Eric Green, director of the National Human Genome Research Institute
Program and free registration: click here
Symposium flyer: download PDF
Can’t make it? Submit your genetic disease-related questions for panel discussion to Nick at nburchfi@sanfordburnham.org. The symposium will be recorded and available on Sanford-Burnham’s website shortly after the event.
Sanford-Burnham’s successful series of Rare Disease Day symposia is based on the concept that treatment of rare diseases requires participation and exchange among all stakeholders—scientists, physicians, affected patients and their families, support groups, granting agencies, industry, and philanthropists. This year’s event, organized by Hudson Freeze, Ph.D., will focus on glycosylation-based disorders.
A few highlights:
- Attendance by several children with Congenital Disorders of Glycosylation who are now benefiting from new therapies
- Lunchtime panel discussion for patients and researchers
- Presentation by patient advocacy group
- Discussion of how one rare disorder relates to Parkinson’s disease
Video and media coverage of last year’s event are available here. For more information about Rare Disease Day USA (February 29, 2012), visit the National Organization for Rare Disorders.
Mayor Hall of Bakersfield cuts the ribbon to open Salon Gianna. Beside him is Gianna, with Dr. Hudson Freeze and her mother, Natalie. On the right are Rocket’s parents, Mia and Taylor Williams, and Gianna’s father, David.
People who care about curing disease can be very creative in finding ways to raise money for research. Whether someone raises money and awareness by walking 60 miles, growing a mustache, or spending $50,000 on a pair of novelty sneakers, people’s passions fuel research funding.
The family that owns Salon Gianna, a beauty salon in Bakersfield, California, is on a mission to find a cure for Congenital Disorders of Glycosylation (CDG). All of their proceeds are earmarked for The Rocket Fund at Sanford-Burnham, which is overseen by Dr. Hudson Freeze. CDG is actually a group of more than 30 rare diseases caused by inherited defects in glycosylation, the process cells use to coat proteins with sugars. Young patients have a broad spectrum of clinical problems often including developmental delay, serious intestinal and liver complications, clotting defects, eye, skin, and other defects. Dr. Freeze’s lab seeks to treat and cure these diseases, often working closely with the families of affected children.
Dr. Fred Levine, director of the Sanford Children's Health Research Center
The Kenneth Rainin Foundation announced that Sanford-Burnham’s Dr. Fred Levine and Dr. Hudson Freeze will receive a 2011 Innovator Award for Inflammatory Bowel Disease (IBD) Research. The team will receive a $100,000, one-year grant for their idea to develop new IBD treatments by targeting a protein called HNF-4a.
HNF-4a is a nuclear receptor, meaning that it directly binds DNA and turns genes on or off in response to outside signals. HNF4a is found throughout the intestine, where it helps maintain structural integrity of the intestinal lining. Previous studies suggest that HNF4a might play a role in IBD. In a mouse model of IBD, lack of HNF4a increased disease severity. HNF4a levels are also low in intestinal biopsy samples from IBD patients. Given this information, it makes sense that enhancing HNF4a function might have the opposite effect, diminishing the disease. However, there hasn’t been a practical way to do that—until now.
Gianna Dragatto, a young patient with a rare disease called Congenital Disorders of Glycosylation (CDG), hopes to see you at Sanford-Burnham's 3rd Annual Rare Disease Symposium on February 24, 2012.
Dr. Eric Green, keynote speaker (photo by Maggie Bartlett)
What: 3rd Annual Sanford-Burnham Rare Disease Symposium
Where: Sanford-Burnham Medical Research Institute, La Jolla, Calif.
When: February 24, 2012
Keynote speaker: Dr. Eric Green, director of the National Human Genome Research Institute (NHGRI) at the NIH
Sanford-Burnham’s successful series of Rare Disease symposia is based on the concept that treatment of rare diseases requires participation and exchange among all stakeholders—scientists, physicians, affected patients and their families, support groups, granting agencies, industry, and philanthropists.
This year’s event, organized by Dr. Hudson Freeze, will focus on Glycosylation-Based Disorders: Discovery, Patients, and Progress Toward Treatments.
Save the date now. Program and registration information will be available soon. In the meantime, video and media coverage of last year’s event are available here.
In the movie Extraordinary Measures, Harrison Ford plays a glycobiologist.
If brides and grooms can have destination weddings, then scientists should be able to have destination research conferences. These types of conferences are increasingly popular as opportunities for scientists to experience fun locales while also interacting and exchanging ideas with a relatively intimate group of expert colleagues. The Gordon Research Conferences have been trendsetters with this format since the 1930s, sponsoring scientific meetings on a variety of topics at sites within the U.S. Starting in 1990, Gordon Conferences have been held in more exotic foreign locations, including Italy, Switzerland, Japan, England, Hong Kong… and even Texas.
Earlier this summer, Dr. Hudson Freeze, program director in Sanford-Burnham’s Sanford Children’s Health Research Center, chaired the Gordon Conference on Glycobiology in Lucca, Italy. 170 glycobiologists from around the world gathered to hear about exciting new developments in the science of carbohydrates (sugar molecules) and the complex molecules like proteins and lipids whose properties are influenced by incorporation of carbohydrates. Once a rather understudied area of biology, glycobiology has been transformed by the realization that carbohydrates mediate many of the key molecular interactions that govern cellular function. Meeting topics included the effects of sugar modifications during development, the role of carbohydrates in normal adult physiology and the involvement of carbohydrates in tissue engineering and repair, including their importance in stem cell biology.
The students in this year's Preuss School UCSD intership program, in Bradley Plaza on the La Jolla campus.
A group of 12 San Diego high school students has been waking up early all week and making the most of their summer break. If you look at their Facebook pages you might see updates saying things things like, “OMG, silencing DAF2 gene in C. elegans–amazing.” An internship program taking place at Sanford-Burnham demonstrates that the right educational opportunities have the power to get young people excited about science and perhaps change their lives.
That was the case for Tony Chau, who completed the Sanford-Burnham/Preuss School UCSD Summer Internship program in 2009. This fall he heads to Duke University, complete with a scholarship, to double major in Biomedical Engineering and Economics. “The internship program helped me greatly through the rest of high school and in applying to college,” he recalls. “The people I met and the experiences I had will stay with me throughout my career.”
Sanford-Burnham scientists are leading several exciting symposia over the next few months. Please follow the links below for more event and registration information.
2011 Signaling, Metabolism and Hypoxia Symposium
Chaired by Dr. Ze’ev Ronai
May 6, 2011, 2:00 – 5:30 p.m. (PDT)
Sanford-Burnham Medical Research Institute
10901 North Torrey Pines Road
La Jolla, California
2011 Glycobiology Gordon Research Conference
Chaired by Dr. Hudson Freeze
May 8 – 13, 2011
Il Ciocco Hotel
Lucca (Barga), Italy
Sanford-Burnham’s 33rd Annual Symposium: Structural Systems Biology
Chaired by members of the Bioinformatics and Systems Biology Program
Drs. Adam Godzik, Dorit Hanein, Andrei Osterman, Niels Volkmann
June 7, 2011, 9:00 a.m. – 5:15 p.m. (PDT)
Hilton La Jolla Torrey Pines
La Jolla, California
Cardiomyocyte Regeneration and Protection
Chaired by Dr. Mark Mercola
Sponsored by Abcam
June 20 – 21, 2011
Hilton La Jolla Torrey Pines
La Jolla, California
2011 Molecular Therapeutics of Cancer Research Conference
Chaired by Dr. Sara Courtneidge
Sponsored by the Cancer Molecular Therapeutics Research Association
July 10 – 14, 2011
Asilomar Conference Center
Pacific Grove, California
Seventh General Meeting of the International Proteolysis Society
Chaired by Dr. Guy Salvesen and Dr. Matthew Bogyo
October 16 – 20, 2011
Hilton San Diego Resort and Spa
San Diego, California
Left: electron microscopy view of actin. Right: Dr. Dorit Hanein's 3-D view.
Life is complicated. Even one tiny cell has a lot going on at any given time, even when things are running smoothly. Normal cellular functions and their emergency responses (like to injury or infection) are mostly carried out by proteins. Proteins tell other proteins what to do by carrying signals, tagging one another with chemical groups, chewing up other proteins or helping assemble new ones, and so on. They also help orchestrate which genes are turned on or off and when.
The cell itself is constantly sensing and reacting to constant environmental fluctuations, as are the individual proteins and other molecules. So how do you connect these two things?
“You can see a cell by eye, using a standard microscope. But you can’t see individual molecules that way,” explains Sanford-Burnham’s Dr. Dorit Hanein. “A cell is on the micrometer scale (one-thousandth of a millimeter), while an individual molecule is on the nanometer scale (one-millionth of a millimeter). That’s like the difference between walking the 500 miles from here [San Diego] to San Francisco, versus walking from here to the moon.”
What Dr. Hanein and other scientists need are techniques that allow them to look not just at the moon, but at the earth, the moon and everything in between.
A video by high school student Daniel Osterman, son of Sanford-Burnham investigator Dr. Andrei Osterman, takes a quick look at the basic biomedical research being conducted at the Institute. In particular, the piece focuses on Dr. Hudson Freeze’s research. Dr. Freeze recently organized Sanford-Burnham’s 2nd Annual Rare Disease Symposium, and studies a group of rare conditions called Congenital Disorders of Glycosolation (CDG), in which sugars fail to attach properly to proteins.