October 4, 2005
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University researchers develop customized DNA chip known as a microarray to diagnose eye disorders
By Rossitza lordanova For the Daily
E mbedded with DNA molecules, that can screen
thrugh thou sands of genetie suences amicrhar;-
rays have recently allowed University researchers
to diagnose an eye disease that once took several
years to detect.
In a study published in the September issue of Investiga-
tive Ophthalmology and Visual Science, a team of research-
ers lead by ophthalmology Prof. Rhada Ayyagari at the
University's Kellogg Eye Center successfully tested microar-
ray technology's ability to diagnose a specific type of retinitis
pigmentosa, also known as RP.
With the new technology, ophthalmology Prof. John
Heckenlively said, patients with the ocular disease can
receive more pre-
cise diagnoses that
will make treatment
"When we have much easier.
RP causes pro-
treatments we gressive retinal
would be better can lead to blind-
able t tellness. It is passed
able to tell
down and affects
who is eligible one out of 3,500
for treatment. wide according to
the Kellogg Eye
It is basically Center.
Currently, the cln-
speeding up cal diagnosis of RP
the process." is largely based
on an individual's
in the eye, loss of
- John Heckenlively, peripheral vision,
night blindness and
ophthalmology professor retinal changes.
and researcher at the But Ayyagari said
Kellogg Eye Center the symptoms of RP
overlap with those
of many other ocu-
lar disorders, making it challenging to provide a definite
While a clinical diagnosis is only the first step, molecu-
lar testing is needed to identify the gene and the mutations
involved that cause the disorder.
Since there are more than 90 different genetic forms of RP
and many forms look alike, manual sequencing techniques to
detect the disease are very time consuming and inefficient.
Rather than rely on arduous diagnosing processes, Ayya-
gari and her team aimed to devise a new technique to detect
the disease by directly analyzing the DNA of an individual
with a microarray.
Chips to Detect Mutations in Retinitis Pigmnentosa Patients
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' .COURTESY OF KELLOGG EYE CENTER
Diagram shows the genetic patterns of retinitis pigmentosa the microarray can detect.
With a microarraythe DNA of a patient can be screened
against multiple genes on a single platform, instead of the
traditional sequencing of one gene at a time.
There are many different genetic patterns that can
indicate the presence of RP. As result, the team used
a microarray to siphon through the genetic patterns.
Microarrays work by measuring changes in gene
expression patterns by comparing one gene pat-
tern with another. A normal microarray would not
be effective in a disease like RP because of the vast
number of mutations that can indicate the disease.
However, Ayyagari and her team employed a
microarray embedded with the specific gene patterns
to detect RP among the hundreds of different varia-
tions found within genes.
Heckenlively at the Kellogg Eye Center examined
the patients who participated in the study.
Thirty-five RP patients were screened using the
microarray containing 11 genes known to cause
RP. The sequences of the genes and mutations the
researchers obtained were 99 percent accurate. At the
same time, 506 sequence changes associated with RP
were detected and 120 of them were not previously
Ayyagari said this result emphasizes the usefulness
of the technique since it not only provides a definite
diagnosis, but also deepens the understanding of the
disorder on a molecular level.
"We're excited about finding mutations in different
genes that would modify other genes," she said.
But there are still drawbacks to the technique: inter-
pretation of the results is time consuming. Research-
ers expect to increase the number of genes that can
be included on the microarray chips to make the tech-
nique more effective.
Still, the use of DNA screening chips is likely to
become even more useful in the future because treat-
ments currently under development to treat RP will
be effective at-treating people with the specific genet-
"That in turn means that when we have treatments,
we would be better able to tell who is eligible for the
treatment. It is basically speeding up the treatment
process" Heckenlively said.
The Kellogg Eye Center is one of the leading cen-
ters for RP research and was among the first centers
to set up a certified molecular diagnostics unit for
retinal degenerations and glaucoma.
Astronomy rapper breaks it
down with dark matter mystery
Discussion is part of lecture
series examining the impact
of Einstein on astronomy
By Michael Kan
Daily Science Editor
While astronomers have yet to completely
deduce the nature of dark matter after more
than seven decades, David Weinberg can break
down its history into a 5-minute rap song.
"Dark matter. What is it? Do we need it?
Where is it?" Weinberg rapped, in the closing
minutes of his lecture on dark matter and dark
In commemoration of Einstein's contribu-
tion to astronomy, the astronomy department's
distinguished lecture series this semester will
examine Albert Einstein's legacy in the field.
Last Friday, Weinberg, an Ohio State Uni-
versity astronomy Prof., spoke on the myster-
ies of dark matter and dark energy that have
dogged astronomers for decades.
Weinberg began his lecture by detailing the
origins of dark matter, adding that astrono-
mers began to notice the phenomenon when
examining abnormal galaxy clusters.
In 1933 Swiss astrophysicist Fritz Zwicky
observed a cluster of galaxies called the
Coma Cluster that according to his measure-
ments, did not exhibit enough gravity to hold
the cluster together.
Zwicky concluded the cluster must contain
something that would produce enough gravity
to hold the galaxies together.
"The galaxies were moving so fast that there
was not enough gravity to hold them together.
So Zwicky decided to call it the missing mass
This "missing mass problem" would later
become known as dark matter,
Not until about the 1970s did the phenom-
enon re-emerge into the field of astronomy,.
Weinberg said. By then astronomers had
observed that the rotational speed of spiral
galaxies did not act according to the rules of
Weinberg used the example of a solar sys-
+em envna that ac nlnnatc mon na o m the
Doctors found that
infection, not stress,
(AP) - Two Australians won the
Nobel Prize in medicine yesterday for a
discovery that defied decades of medical
dogma and revolutionized the treatment
of ulcers. They showed that bacterial
infection - not stress - causes ulcers
in the stomach and intestine.
The 1982 discovery by Drs. Barry
Marshall and Robin Warren eventually
transformed peptic ulcer disease from a
chronic, frequently disabling condition to
one that can be cured by a short regimen
of antibiotics and other medicines, said the
Nobel Assembly of the Karolinska Insti-
tute in Stockholm.
Marshall, 54, and Warren, 68, discov-
ered the bacterium Helicobacter pylori and
uncovered its role in causing ulcers and
stomach inflammation. The prize, with its
$1.3 million check, gives the ultimate vali-
dation to an idea that initially drew skepti-
cism and derision.
The Australians' bacterial theory of
ulcers was "very much against prevail-
ing knowledge and dogma," Staffan Nor-
mark, a member of the Nobel Assembly,
said at a news conference in Stockholm.
Most doctors believed ulcers came from
stress and stomach acid.
To make his case, Marshall even delib-
erately infected himself by swallowing a
culture of H. pylori.
"I developed a vomiting illness and
had severe inflammation in the stomach
for about two weeks," he told The Associ-
"I didn't actually develop an ulcer, but
I did prove that a healthy person could be
infected by these bacteria, and that was
an advance because the skeptics were
saying that people with ulcers somehow
had a weakened immune system and that
the bacteria were infecting them after the
The two researchers began working
together in 1981. "After about three years
we were pretty convinced that these bac-
teria were important in ulcers and it was
a frustrating time for the next 10 years
though because nobody believed us," said
Marshall, a researcher with the University
of Western Australia.
"The idea of stress and things like that
was just so entrenched nobody could really
believe that it was bacteria. It had to come
from some weird place like Perth, West-
ern Australia, because I think nobody else
would have even considered it."
Dr. David Peura, president of the Ameri-
can Gastroenterological Association, said
the prize-winning work "revolutionized our
understanding of ulcer disease" and "gave
millions of people hope."
He read about the H. pylori theory in
1983 while serving as a gastroenterologist
in the Army, and "I thought it was crazy,"
he recalled yesterday.
But he and a colleague were intrigued,
and soon they discovered they could cure
ulcers in their own patients with antibiotics
targeted at H. pylori.
"It was such an intriguing theory that
everybody tried to disprove it and couldn't,
so we all became believers," said Peura,
now a professor of medicine at the Univer-
sity of Virginia at Charlottesville.
Peura, who met Marshall when both
worked at Virginia and considers him a
friend, said Marshall's perseverance was
responsible for the eventual acceptance of
the theory. "Any lesser of a person prob-
ably would not have been able to withstand
some of the ridicule and scorn that was
thrown at him initially," Peura said.
As the two Nobel winners celebrated
with family over champagne and beer in
Perth, the Western Australia state capital,
Warren said he was "very excited, also a
"Obviously, it's the best thing that can
ever happen to somebody in medical
research. It's just incredible," added Mar-
shall in a telephone interview.
Ohio State University astronomy Prof. David Weinberg talks about the history of dark matter
and dark energy.
Since those observations, astronomers
wolrlwide have attemnted to shed light on
other. This unknown force is called dark ener-
2v and has astronomers even more nuzzled.