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- Posted Friday December 12, 2014
New test developed at TGen uses the unique genetics of women to uncover a devastating neurologic disorder
Study published today by investigators with TGen's Dorrance Center for Rare Childhood Disorders
PHOENIX, Ariz. - Dec. 12, 2014 - Using a
basic genetic difference between men and women, the Translational
Genomics Research Institute (TGen) has uncovered a way to track
down the source of a neurological disorder in a young girl.
TGen's discovery relies on a simple genetic fact: Men have one X
and one Y chromosome, while women have two X chromosomes. This
women-only factor was leveraged by TGen investigators to develop a
highly accurate method of tracking down a previously unrecognized
disorder of the X-chromosome.
The study of a pre-teen girl, who went years with an undiagnosed
neurobehavioral condition, was published today in the scientific
journal PLOS ONE.
TGen's findings were made within its Dorrance Center for Rare
Childhood Disorders, where investigators and clinicians apply the
latest tools of genomic medicine to provide answers for parents
seeking to identify the disease or disorder affecting their
child.
The scientists sequenced, or spelled out in order, the complete
genetic codes of DNA and RNA of the girl. Because girls inherit an
X chromosome from each of their parents (boys inherit a Y
chromosome from their father), they also sequenced her mother and
father. On average, about half of all X chromosomes active in a
female come from the mother and the other half from the
father.
"We now have the tools to significantly accelerate the diagnostic
process, reducing the need for children to undergo multiple tests
that can be emotionally and physically taxing for the entire
family," said Dr. David Craig, TGen's Deputy Director of
Bioinformatics, Co-Director of the Dorrance Center and the paper's
senior author.
Sequencing would reveal the proportion of X chromosomes, and if
disproportionate, whether the more abundant of the two were damaged
in some way, which often leads to X-linked genetic
conditions.
"At the time of enrollment, we suspected the girl had a complex
neurobehavioral condition, based on her attention deficit, and
delays in development and learning," said Dr. Vinodh Narayanan,
Medical Director of the Dorrance Center. "Her brain MRI scans were
normal. We needed to find out more - at the genetic level - about
what might be causing her disorder."
By sequencing the DNA and RNA, TGen investigators were able to
precisely identify which cells contained active X chromosomes from
the girl's mother, which contained active X chromosomes from the
father, in what proportions, and whether they were associated with
any known disorders.
They discovered that the X chromosome from the father contained a
segment shown to be associated with neurobehavioral conditions.
Interestingly, however, the proportion of X chromosomes active in
the girl's cells skewed toward the normal X inherited from her
mother. This skewing may have led to a milder, harder to diagnose
condition undetected by conventional methods.
"This study shows the power sequencing holds when scanning for
potential disease causing and disease-modifying genetic
variations," said Dr. Matt Huentelman, the other Co-Director of the
Dorrance Center and an author of the PLOS ONE paper. "I'm
most excited to see the pace at which TGen has pushed the genome
sequencing technology to where it can help patients - today."
TGen Research Associate Szabolcs Szelinger, an Arizona State
University graduate student in Molecular and Cellular Biology and
the paper's lead author, said: "With just a small bio sample, we
are now able to provide a comprehensive evaluation of the effects
that genetic variation has on patients, leading to highly
personalized treatment options, while at the same time providing
researchers with insights into the underlying molecular
processes."
Since opening in October 2013, TGen's Dorrance Center for Rare
Childhood Disorders Dorrance Center has enrolled nearly 300
families. And with the rapid decrease in sequencing costs and
improved analytical methods, comprehensive, integrative sequencing
approaches will likely be used more in the future. Information on
the Dorrance Center is available at www.c4rcd.org.
Funding for the study came from the State of Arizona, the Stardust
Foundation, and donations to the TGen Foundation.
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About TGen
Translational Genomics Research Institute (TGen) is a Phoenix,
Arizona-based non-profit organization dedicated to conducting
groundbreaking research with life changing results. TGen is focused
on helping patients with cancer, neurological disorders and
diabetes, through cutting edge translational research (the process
of rapidly moving research towards patient benefit). TGen
physicians and scientists work to unravel the genetic components of
both common and rare complex diseases in adults and children.
Working with collaborators in the scientific and medical
communities literally worldwide, TGen makes a substantial
contribution to help our patients through efficiency and
effectiveness of the translational process. For more information,
visit:www.tgen.org.
Press Contact:
Steve Yozwiak
TGen Senior Science Writer
602-343-8704
[email protected]