Bedouin tribe reveals secrets to McGill's GA-JOE
'RaDiCAL' approach to gene discovery opens doors to
better understanding of human diversity and
health.
Van Den Ende-Gupta syndrome (VDEGS) is an extremely rare genetic
disorder that is characterized by distinctive head and facial
features, such as unusual eyelids, narrow and beaked noses, flat
nasal bridges, jaw deformities, and a turned out lower lip. As part
of McGill's "RaDiCAL" project (Rare Disease Consortium for
Autosomal Loci), collaborators in Qatar conducted field research
with three patients from biologically interrelated Bedouin
families, and sent samples to Canada for analysis by GA JOE – a
high-tech genome analyzing machine. The research effort was led by
husband and wife team Dr. Jacek Majewski and Dr. Loydie A.
Jerome-Majewska, both of Ï㽶ÊÓƵ's Department of Human
Genetics and the Research Institute of the Ï㽶ÊÓƵ Health
Centre. The team discovered that mutations in the gene SCARF2 are
responsible for the condition, and published their findings online
today in the American Journal of Human Genetics.
"Why is this interesting? One of my roles at McGill is to implement
new genomic technologies in human genetics research," explained
Majewski. "Essentially, with a new technique known as exome capture
and sequencing, we can now quickly sequence all of the coding
portions of the human genome. This approach allows us to identify
mutations responsible for rare genetic disorders. While they were
too rare to attract much interest, these disorders hold in fact a
lot of promise for the identification of the genes and pathways
that are involved in generating human diversity. Moreover, knowing
the mutations will be essential for future genetic testing and
potential therapeutic intervention."
SCARF2 may for instance be involved in DiGeorge Syndrome, a much
more common disorder affecting 1:3000 live births. DiGeorge
syndrome causes deformities such as congenital heart defects. The
researchers caution however that drawing links at this stage
amounts to nothing more than "tantalizing speculation."
In anticipation of the fast advances in technology, McGill is
identifying as many of the genes responsible for rare disorders as
possible. "Over the past couple of years we've been identifying
collaborators worldwide and collecting patients and DNA samples for
mutation hunting," Majewski said. "This is one of the earliest
successes of this project, which is still a hybrid of old and new
technologies. In this particular case, although we found the
mutation the old fashioned way, we had immediate confirmation using
exome sequencing."
"To me the current manuscript is an early example of the enormous
power of new exome/genome sequencing approaches and of the
involvement of McGill researchers in this field," Majewski
concluded. "It really is a harbinger of more to come."
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This research received funding from the Canada Institutes for
Health Research, the Research Institute of the Ï㽶ÊÓƵ
Health Centre, and a Canada Research Chair award to Majewski. Field
research was carried out by the Qatar Medical Genetic Center. Led
by Dr. Tawfeg Ben-Omran, the Qatar Medical Genetic Center is
staffed by expert clinical geneticists and dysmorphologists, who
have developed specific areas of expertise, providing a foundation
for excellent family-centred care. The sequencing was carried out
in close collaboration with the staff of the Genome Quebec
sequencing facility.