Imagine the day that you start to discover new genetic diseases and
perhaps get to name them. This is happening now! Please be aware
that gene testing will make the practice of medicine more exciting
than it has ever been, since there will be reasons for the problems
we see and ANSWERS, as to what we can do to improve the situation.
Please read this carefully, as Dr Yasko will be introducing the
excitement of gene testing combined with RNA based "personalized"
therapies at ACAM on Saturday, November 12 at 8:30 am along with the
introduction of her new book, available that day, for the first
time, on how to interpret genetic testing.
Garry F. Gordon MD, DO, MD(H)
President, Gordon Research Institute
http://www.gordonresearch.com October 10, 2005 08:00 AM US Eastern Timezone
Doctors in Pennsylvania Dutch Country Find New Genetic Links to Half
Dozen Diseases in Past Year
LANCASTER, Pa. & SANTA CLARA, Calif.--(BUSINESS WIRE)--
Oct. 10, 2005
Microarray-Based SNP Analysis Provides Researchers with
Faster, Cheaper and More Definitive Method to Identify and Diagnose
Genetic Disorders
In a corner of Pennsylvania Dutch country, doctors at the Clinic for
Special Children are using Affymetrix GeneChip(R) microarrays to
discover the genetic causes of disease at an unprecedented pace --
more than a half dozen diseases in the past 12 months. In last
month's early on-line issue of American Journal of Medical Genetics,
the small group of physicians reported their most recent discovery:
a mutated gene causing a mysterious developmental disorder in the
Mennonite population.
The non-profit, community-supported Clinic -- part of their budget
comes from their annual quilt sale -- is staffed by medical director
Holmes Morton, MD, pediatrician Kevin Strauss, MD, and geneticist
Erik Puffenberger, PhD. Morton and his wife Caroline started the
clinic nearly 20 years ago to try to find treatments for a variety
of rare genetic diseases that have long afflicted children in Plain
sect communities, such as the Amish. In just the past year though,
using a new GeneChip microarray technology from Affymetrix
(Nasdaq:AFFX), Morton and colleagues have made breakthrough
discoveries for genetic causes of at least six different diseases.
While these scientists are studying diseases far more common in the
Plain sects, their findings have worldwide ramifications, providing
the basis for genetic tests of rare diseases in the general
population.
The most recent discovery began when the parents of a 4 year-old
girl suffering from slow growth and developmental delay informed the
Clinic doctors of a cousin with similar symptoms, raising suspicion
that the disease was hereditary. While recent estimates place about
25,000 genes in the human genome, the team narrowed their search to
just 55 genes on chromosome 6 by using GeneChip Mapping 10K
microarrays to scan 10,000 genetic variations from the two affected
cousins and each of their parents. The team suspected two of the
genes were involved in the disease and found that one of them --
SLC17A5 -- was mutated in the developmentally-delayed patients. The
mutation turned out to be the identical one that causes Salla
disease in the Finnish population; the Clinic physicians were then
able to diagnose Salla disease in 4 additional individuals by
testing for the SLC17A5 mutation directly in patients who had
similar disease symptoms.
"Our most recent study using GeneChip arrays took less than one
month to complete and cost less than $4,000 dollars to make a
definitive diagnosis of Salla disease," said Strauss. "That same
patient had undergone four years of standard medical exams, totaling
nearly $20,000 dollars, but the diagnosis was elusive until we
looked at her genome with the 10K microarray."
Affymetrix Microarray Technology
The key to these doctors' genetic discoveries is that they used the
10K microarray to look at the genome more quickly, more affordably,
and in far greater detail than ever before. The experiments are not
complicated. The scientists process only a handful of DNA samples
and use little more than Microsoft(R) Excel for their statistical
analyses. However, these physician-scientists work closely with
their patients to understand disease symptoms; they then tease out
causative mutations using high-density GeneChip microarrays as a
powerful lens to view their patients' genomes, uncovering any hidden
mutations.
To accelerate their discoveries, Affymetrix has donated a GeneChip
system to the Clinic for Special Children; the donation comprises an
annual number of GeneChip microarrays, a FS400 Fluidics Station to
perform the microarray experiment, a GCS 3000 Scanner to image the
microarrays, and all the software required to control the system and
analyze array data.
"The goal is to identify the molecular lesions causing disease in
our patient population. With this information, we can perform
molecular genetic testing and identify affected individuals before
they are symptomatic," said Puffenberger. "Currently, the most
effective tool for us to map disease genes and identify the disease-
causing mutations is the GeneChip mapping array."
Other Recent Findings
1. Cortical Dysplasia and Focal Epilepsy
The Clinic team used the 10K to scan the genome of four Amish
patients and mapped the disease mutation to a small part of
chromosome 7 containing 83 genes. The scientists sequenced two of
those genes in their patients and identified a single base deletion
in all four patients. By screening all their seizure patients for
this mutation, they were able to diagnose six other children with
the same condition (research publication forthcoming).
2. "Pretzel" syndrome
Studying just seven families, each with at least one affected child,
the Clinic team discovered a small genetic deletion in a single gene
located on chromosome 17 that had been previously missed. They made
the discovery by noticing that one of the 10,000 SNPs on the
microarray was missing in all seven patients; that missing SNP was
part of the DNA deleted in the Pretzel syndrome patients (research
publication forthcoming).
Pretzel syndrome is a previously undescribed disorder characterized
by skeletal deformity, malformation of the brain (with accompanying
seizures), electrolyte imbalances, and variable malformations of the
heart and other organs.
3. Down Syndrome, Patau Syndrome and other chromosomal disorders
Using microarrays to genotype 10,000 SNPs from infants seen at the
Clinic, the team quickly detected chromosomal copy number disorders
like Trisomy 21 (Down syndrome) and Trisomy 13 (Patau syndrome) that
are caused by having too many or too few chromosomes. With a basic
10K microarray scan, they found one patient with trisomy 13,
confirmed two suspected cases of Down, identified a deletion on
chromosome 13 in another patient, and discovered a 23 megabase
duplication of chromosome 2 in yet another patient (research
publication forthcoming).
Trisomy occurs when a patient has three chromosomes instead of two,
and is typically diagnosed by looking for extra chromosomes with a
microscope. While SNP genotyping can confirm simple diagnoses of
common chromosome duplications, they can also detect duplications or
deletions of small parts of chromosomes that cause similar
hereditary disease and are more difficult to diagnose than having an
extra chromosome.
4. Sudden Infant Death with Dysgenesis of the Testes (SIDDT)
The scientists identified a gene linked to a form of the largely
mysterious sudden infant death syndrome (SIDS). While the genetic
basis of SIDS has eluded scientists for decades, the group used the
Affymetrix 10K array to analyze the DNA of just four infants, along
with their family members, and within two weeks had found the
mutation. The Clinic research team published these findings in the
August 2004 issue of PNAS.
Upcoming studies
The researchers are currently planning to study a group of over 200
children with undiagnosed developmental delays to find the inherited
mutations responsible for disease. Using the 10K array, the team
will compare SNP genotypes between their patients with unexplained
developmental delay. By grouping patients with the most similar
clinical features, they hope to identify shared genomic regions,
locate potential candidate genes, identify mutations, and ultimately
make a genetic diagnosis. Other ongoing studies include combined
variable immune deficiency, epilepsy, and cardiomyopathy.
"These Plain sect studies at the Clinic for Special children are a
perfect example of how GeneChip microarrays are enabling scientists
to explore the human genome and quickly discover the mutations
underpinning disease -- it's a glimpse into the future of medicine,"
said Greg Yap, vice president of DNA Products at Affymetrix. "While
10,000 SNPs work well for studying small familial populations,
100,000 SNP products and 500,000 SNP products are doing the same
thing for studies of complex diseases like diabetes and
hypertension."
Broader Implications
Scientists elsewhere are discovering the genetics behind common
complex diseases, like hypertension and diabetes, taking an approach
similar to the Clinic for Special Children doctors, but using
microarrays with far more processing power. Instead of 10,000 SNPs,
scientists like Josephine Hoh at Yale University are able to hone in
on disease associated mutations by using microarrays that genotype
hundreds of thousands of SNPs; these microarrays provide enough
genetic information to filter out the normal DNA differences between
unrelated people that share the same disease. Hoh's recent study,
published in the April 2005 issue of Science, scanned 100,000 SNPs
from just 146 people to find a mutation associated with age related
macular degeneration. Using previous technologies that looked at far
fewer SNPs to generate results with the same scientific significance
would have required Hoh to study thousands of people.
About The Clinic for Special Children:
The Clinic for Special Children is a non-profit diagnostic and
pediatric medical service for children with genetic disorders in
Lancaster County, PA. The clinic was established to provide
comprehensive medical care and affordable diagnostic and laboratory
services for children with chronic, complex health problems due to
inherited disorders. The mission of the clinic also includes
improving newborn screening and follow-up services, developing more
effective diagnostic methods, advancing clinical research, and
acting as an educational resource for those who seek to provide care
for children who suffer from rare, inherited diseases.
About Affymetrix:
Affymetrix scientists invented the world's first microarray in 1989
and began selling the first commercial microarray in 1994. Since
then, Affymetrix GeneChip(R) technology has become the industry
standard in molecular biology research. Affymetrix technology is
used by the world's top pharmaceutical, diagnostic and biotechnology
companies as well as leading academic, government and not-for-profit
research institutes. More than 1,200 GeneChip systems have been
shipped around the world and more than 3,000 peer-reviewed papers
have been published using the technology. Affymetrix' patented
photolithographic manufacturing process provides the most
information capacity available today on an array, enabling
researchers to use a whole-genome approach to analyze the
relationship between genetics and health. Headquartered in Santa
Clara, Calif., Affymetrix has subsidiaries in Europe and Asia in
addition to manufacturing facilities in Sacramento, Calif. and
Bedford, Mass. The company has about 900 employees worldwide. For
more information about Affymetrix, please visit the company's
website at
http://www.Affymetrix.com All statements in this press release that are not historical
are "forward-looking statements" within the meaning of Section 21E
of the Securities Exchange Act as amended, including statements
regarding Affymetrix' "expectations," "beliefs," "hopes," "intentions," "strate
gies" or the like. Such statements are subject to risks and
uncertainties that could cause actual results to differ materially
for Affymetrix from those projected, including, but not limited to
risks of the Company's ability to achieve and sustain higher levels
of revenue, higher gross margins, reduced operating expenses,
uncertainties relating to technological approaches, manufacturing,
product development (including uncertainties relating to the use of
the genotyping arrays and outcome of research discussed in this
press release), personnel retention, uncertainties related to cost
and pricing of Affymetrix products, dependence on collaborative
partners, uncertainties relating to sole source suppliers,
uncertainties relating to FDA and other regulatory approvals,
competition, risks relating to intellectual property of others and
the uncertainties of patent protection and litigation. These and
other risk factors are discussed in Affymetrix' Form 10-K for the
year ended December 31, 2004 and other SEC reports, including its
Quarterly Reports on Form 10-Q for subsequent quarterly periods.
Affymetrix expressly disclaims any obligation or undertaking to
release publicly any updates or revisions to any forward-looking
statements contained herein to reflect any change in Affymetrix'
expectations with regard thereto or any change in events,
conditions, or circumstances on which any such statements are based.
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