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| TASC Genetic Study
Uncovers Two New Genes Implicated In Ankylosing
Spondylitis |
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Good news, in 2007 two new genes
identified as ARTS1* and IL-23R* have been implicated in
ankylosing spondylitis. This new finding means that
researchers now have uncovered roughly 70% of the
genetic contribution toward susceptibility toward AS.
What does this mean for patients?
This new information resulting from the work coming out
of the TASC genetic study, headed by Drs. John D.
Reveille and Matthew Brown, provides two more critical
pieces of the puzzle with regard to unraveling the
mystery of how AS develops. Further, the discovery of
IL-23R could very likely lead to new biological
medicines in the treatment of AS with new clinical
trials beginning as early as within two years. The
reason for this likelihood is that IL-23R has already
been implicated in Crohn’s Disease and as a result
research has already begun to develop a class of drugs
specific to this gene target. What is more, researchers
are suggesting that eventually these findings very
likely will lead to a faster diagnosis for people who
show early symptoms of AS.
Who conducted the study?
Work done in part by the Australo-Anglo-American
Spondylitis Consortium (TASC), which includes the SAA,
led to the discovery of the two genes. The findings,
which were announced in the
Nov. 2007 issue of Nature,
Genetics, resulted from the largest and most
comprehensive genome-wide association scan ever
conducted to date. Several other unrelated diseases were
included in this scan. These included breast cancer and
multiple sclerosis, but according to the AS researchers,
it is encouraging to note that most significant findings
were in AS.
How did genetic studies all get started?
In 1944, three researchers at Rockefeller University
published a paper that laid a foundation for the modern
revolution called molecular biology. By discovering that
DNA is the material that is involved in transmitting
genetic information, the good and the not-so-good, from
one generation to the next, Avery, MacLoed and McCarty
paved the way for the work later picked up by Crick,
Watson and Wilkins in the early 1950s, which eventually
led to a Nobel Prize award for elucidating DNA’s
structure.
What many people do not realize is that the original
pivotal work actually was driven by the quest to
understand a specific disease; pneumonia. During that
epoch—in the early decades of the 20th century,
pneumonia was the leading cause of death in America. It
was responsible for the premature death of more people
than cancer or heart disease.
Without the investigation of how certain types of
pneumonia “transformed” into others, the discovery that
DNA carried genetic information would most likely not
have been uncovered as early as it did.
Fast forward to the 1970s
Humans have roughly between 20,000 and 25,000 genes, but
according to researchers, fewer than a dozen most likely
play any significant role in AS. The first of these
genes, HLA-B27, was discovered in the 1970s. At that
time this was a spectacular and important discovery to
aid diagnosis in some patients, and also led to be
better understanding of the worldwide distribution of
the disease in different populations, since it was
recognized early on that the rate of HLA-B27 in
population largely determined the likely prevalence of
AS.
It is thought that HLA-B27 accounts for approximately 40
percent of the overall cause of AS, and now with this
new discovery, according to Drs Reveille and Brown,
together with B27, the identified genetic susceptibility
toward AS now stands at roughly 70 percent of the
overall cause.
What does the future hold?
Research typically advances in micro-steps that are
barely perceptible even within the scientific community
itself. However, this discovery is much more significant
with far reaching potential. Indeed, the researchers
tell us that the identification of these new genes will
become part of the AS permanent record upon which new
and important future advances will be made.
In an interview with Spondylitis Plus from Brisbane,
Australia, Dr. Matthew Brown stated that the scan that
identified these two genes looked at around 15% of the
genetic diversity between individuals, and that going
forward the Australo-Anglo-American Spondyloarthritis
Consortium study (TASC) will survey 80-85% of that
diversity, and so is likely to find still more genes. He
concluded, “We can expect really major advances then
over the next 5 years in AS research on the back of
these genetic studies - these are very exciting times
indeed.”
The SAA acknowledges with deep gratitude the work of
Drs. Reveille and Brown and their TASC team, in addition
to the researchers at the Wellcome Trust in Oxford, UK,
who have made this discovery possible.
How is AS triggered in a person?
Many AS researchers think that AS occurs because people
carrying particular combinations of genes are exposed to
some common environmental trigger, most likely some
bacteria that we carry in the gut. This suggests that It
is likely that nearly everyone is exposed to the
trigger, but only those with particular combinations of
genes develop the disease.
What is DNA?
DNA, or deoxyribonucleic acid, is the hereditary
material in humans and most other organisms. Most DNA is
located in the cell nucleus (where it is called nuclear
DNA), but a small amount of DNA can also be found in the
mitochondria, where it is called mitochondrial DNA or
mtDNA.
The information in DNA is stored as a code made up of
four chemical bases: adenine (A), guanine (G), cytosine
(C), and thymine (T). Human DNA consists of about 3
billion bases, and more than 99 percent of those bases
are the same in all people. The order, or sequence, of
these bases determines the information available for
building and maintaining an organism, similar to the way
in which letters of the alphabet appear in a certain
order to form words and sentences.
DNA bases pair up with each other, A with T and C with
G, to form units called base pairs. Each base is also
attached to a sugar molecule and a phosphate molecule.
Together, a base, sugar, and phosphate are called a
nucleotide. Nucleotides are arranged in two long strands
that form a spiral called a double helix. The structure
of the double helix is somewhat like a ladder, with the
base pairs forming the ladder’s rungs and the sugar and
phosphate molecules forming the vertical sidepieces of
the ladder.
An important property of DNA is that it can replicate,
or make copies of itself. Each strand of DNA in the
double helix can serve as a pattern for duplicating the
sequence of bases. This is critical when cells divide
because each new cell needs to have an exact copy of the
DNA present in the old cell.
Reference: NIH.gov
Glossary:
The unabbreviated name for the IL23R gene is
“interleukin 23 receptor”
The unabbreviated name for the ARTS1 gene is “type 1
tumor necrosis factor receptor shedding aminopeptidase
regulator”
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