Personalized Medicine “It doesn't get more personal than this.”

Prof. Karen
Avraham
6
Specific Pathogen Free (SPF) Facility
housed in the David and Inez Meyers
Building for Transgenic Modeling of
Human Disease, won the Israel Prize
for 2011 and EMET Prize in 2005 for
his work.
Diagnosing or preventing
common diseases
Mining people’s genetic material can
unearth the cause of prevalent disorders,
not just rare ones.
Prof. Karen Avraham began working
on hereditary deafness when she
joined the Sackler Faculty of Medicine’s
Department of Human Molecular
Genetics and Biochemistry in 1996.
About 50% of hearing impairment
can be traced to genetic causes, and
Avraham was intrigued to learn that,
in the Middle East, many extended
families and clans were known to have
a much higher incidence of deafness
than the rest of the population.
Prof. Avraham quickly established
connections with clinical genetic labs all
over Israel, as
well as in the
Palestinian
Aut horit y,
and has since
performed a
number of
studies on
families and
villages that
generated scientific gold: the discovery
of 10 new genes implicated in hearing
loss. Major funding for this work has
come from the United States’ Office of
American Schools and Hospitals Abroad
(ASHA), which supports a Laboratory
for Middle Eastern Genetic Diseases
at TAU.
One Jewish clan that Avraham studied
came originally from Mosul, Iraq.
Intermarriage among extended family
members had led to 40% of all offspring
going deaf by the age of 20 – compared
to less than 1% in the general population.
Avraham and her team found the
responsible gene and also determined
that it was recessive, that is, both parents
had to have it. Armed with this
information, medical geneticists could
provide genetic counseling.
“Here’s the most satisfying part,”
says Avraham. “By working with doctors
and fine-tuning genetic testing for
family members, we could break the
chain of inheritance.”
Among Avraham’s latest discoveries
is the mechanism by which auditory
cells die in the ear. This finding is important
for possibly rescuing these cells,
or regenerating them, in the future.
But what excites her most is a method
she’s developed in collaboration with
Prof. Moien Kanaan from Bethlehem
University for improved diagnosis of
genetic hearing loss in patients. “Until
fairly recently, researchers could test for
one or a few deafness genes at a time,
a costly, hit-or-miss process that could
take years,” explains Avraham. “With
our new method, we can scan all the 250
known genes for deafness – simultaneously
– for less than $500 per person,
and provide results in a few weeks.”
The joint Israeli-Palestinian research,
funded by the United States’ National
Institutes of Health (NIH), capitalizes
on a shortcut gene sequencing technology
called “exome sequencing.” It scans
just those regions of DNA that encode
proteins – regions that comprise only
1% of the human genome but that are
implicated in about 85% of diseasecausing
mutations.
“The important thing about this
technology – and about genomic
medicine in general – is that the faster,
cheaper methods can bring about
much earlier diagnoses for diseases,”
says Avraham. “And the earlier and
more accurate the diagnosis, the better
doctors can predict the course of the
disease and prescribe treatment.
Determining risk
Pinpointing who is at greater genetic
risk for complex diseases such as
This machine reads faster than
you do. Dr. Noam Shomron by
the genome high-throughput
sequencing machine on campus.
cancer, diabetes and heart disease is
“tricky” says new faculty member Eran
Halperin. He combines his knowledge
in human genetics, computer science
and mathematics to sleuth out diseasecausing
mutations.
“We might find a common gene variant
that seems to be associated with a
certain type of cancer,” Dr. Halperin
elaborates, “but there’s no one-to-one
correspondence. We can’t say with certitude
that people who have the mutated
gene will get the disease, or that people
who don’t have the mutated gene will
not get the disease.
“Other, more hard-to-find mutations
may also be involved in triggering
the cancer, in combination with
each other or with environmental and
lifestyle factors.”
Halperin, who has a joint appointment
at the Blavatnik School of
Computer Science and the Department