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Archive for the ‘Gene Therapy Research’ Category

It's in their DNA: 'Speed gene' of greatest ever thoroughbreds traced back to ONE horse 300 years ago

Gene traced back to single 17th century British
mare

Experts analysed data from nearly 600
horses

By Chris Parsons

Last updated at 9:44 AM on 28th January 2012

They are some of the world's greatest ever horse racing
names, but new research has suggested that the likes of
Seabiscuit, Man O'War, Secretariat and Seattle Slew may all
have a distant genetic connection.

Researchers have claimed that all the best thoroughbreds
of racing are all very distantly related after tracing the
'speed gene' they all share to a single ancestor from the 17th
century.

Experts at University College Dublin analysed DNA from
nearly 600 horses and 22 modern breeds, and were able to
predict what the horses had in common genetically.

Scientists analysing horse DNA traced the 'speed gene' back
to a single British mare in the 17th century

Their results showed how the 'speed gene' which saw
racing greats like Man O'War and Seabiscuit power to victory
was passed to the famous horses from a single founder, a
British mare around 300 years ago.

The British ancestor was racing in the mid-17th century
at a time when local British breeds were pre-eminent in racing
horses and before the foundation of the thoroughbred
racehorse.

 

In finding the 'speed gene', a C type myostatin gene
variant, researchers studied genetic data from hundreds of
horses, as well as the skeletal remains of 12 thoroughbred
stallions born between 1764 and 1930.

Their research also included DNA from 330 elite
performing thoroughbreds, 40 donkeys and two zebras.

Legend: U.S. thoroughbred Seattle Slew remains the only horse
to win the Triple Crown while undefeated

Iconic: Man O'War, thought to be one of the greatest
thoroughbreds of all time, won 20 of his 21 races.

Record breaker: U.S. horse Secretariat set records in two
Triple Crown races which still stand to this day

Famous: Seabiscuit became the subject of a book and two films
followings its success

Modern variants recently traced successful thoroughbreds
back to legendary mare Nearctic, who lived between 1954 and
1973.

The variant branched out to Nearctic's son Northern
Dancer, which according to LiveScience was the most bred
stallion of modern times.

Norther Dancer never finished lower than third and won 14
of his 18 races.

But the new research has now traced the success of modern
thoroughbreds back to a single horse over 300 years ago.

Researcher Emmeline Hill, a genomics scientist at
University College Dublin who led the study, said: 'Changes in
racing since the foundation of the Thoroughbred have shaped the
distribution of 'speed gene' types over time and in different
racing regions.

Research: Dr Emmeline Hill, pictured with Irish trainer Jim
Bolger, conducted the study to discover the genetic links
between successful thoroughbreds

'But we have been able to identify that the original
'speed gene' variant entered the Thoroughbred from a single
founder, which was most likely a British mare about 300 years
ago.

'Having first identified the 'speed gene' in 2010, we
decided to see if we could trace the origin of the gene variant
using population genetics coupled with pedigree
analysis.

'We wanted to understand where speed in the Thoroughbred
came from.'

Researchers said all great sprinting horses shared two
genes associated with muscle development.

The genetic combination was not present in regular farm
horses, donkeys or zebras.

 

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It's in their DNA: 'Speed gene' of greatest ever thoroughbreds traced back to ONE horse 300 years ago

Body clock gene 'link' to diabetes

Defective versions of a "body clock" gene greatly increase the
risk of type 2 diabetes, a study has shown.

The discovery provides new evidence of a link between the
body's sleep cycle, governed by the hormone melatonin, and the
disease.

Previous research has found that people who work night shifts
are more at risk of type 2 diabetes and heart disease.
Volunteers who have their sleep disrupted repeatedly for three
days also develop temporary diabetic symptoms.

Melatonin controls the body's cycle of sleeping and waking,
inducing drowsiness and lowering body temperature. For this
reason melatonin supplements are often taken to combat jet-lag.

The new study focused on a gene called MT2 which codes for the
molecular cell receptor that allows melatonin to work. Carrying
any of four rare mutations in the gene increased the risk of
developing type 2 diabetes six times, the research showed.
Faulty MT2 is thought to disrupt the link between the body
clock and insulin release, leading to abnormal control of blood
sugar and diabetes.

The findings are published in the journal Nature Genetics.

Study leader Professor Philippe Froguel, from Imperial College
London, said: "We found very rare variants of the MT2 gene that
have a much larger effect than more common variants discovered
before. Although each mutation is rare, they are common in the
sense that everyone has a lot of very rare mutations in their
DNA. Cataloguing these mutations will enable us to much more
accurately assess a person's risk of disease based on their
genetics."

More than two million people in the UK are known to suffer from
type 2 diabetes, the most common form of the disease, which is
linked to obesity and lifestyle.

The Imperial team and other scientists from the UK and France
looked at the MT2 gene in the DNA of 7,632 people. They found
40 variants associated with type 2 diabetes, including four
that were very rare and rendered the receptor completely
incapable of responding to melatonin. The link with the four
mutations was then confirmed in an even bigger sample of 11,854
people.

The scientists tested the effects of the defective genes in
human cells in the laboratory. They found the mutations had a
major impact on type 2 diabetes risk.

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Body clock gene 'link' to diabetes

Body clock receptor linked to diabetes in new genetic study

Public
release date: 29-Jan-2012
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Contact: Sam Wong
sam.wong@imperial.ac.uk
44-207-594-2198
Imperial College
London

A study published in Nature Genetics today has found new
evidence for a link between the body clock hormone melatonin
and type 2 diabetes. The study found that people who carry rare
genetic mutations in the receptor for melatonin have a much
higher risk of type 2 diabetes.

The findings should help scientists to more accurately assess
personal diabetes risk and could lead to the development of
personalised treatments.

Previous research has found that people who work night shifts
have a higher risk of type 2 diabetes and heart disease.
Studies have also found that if volunteers have their sleep
disrupted repeatedly for three days, they temporarily develop
symptoms of diabetes.

The body's sleep-wake cycle is controlled by the hormone
melatonin, which has effects including drowsiness and lowering
body temperature. In 2008, a genetic study led by Imperial
College London discovered that people with common variations in
the gene for MT2, a receptor for melatonin, have a slightly
higher risk of type 2 diabetes.

The new study reveals that carrying any of four rare mutations
in the MT2 gene increases a person's risk of developing type 2
diabetes six times. The release of insulin, which regulates
blood sugar levels, is known to be regulated by melatonin. The
researchers suggest that mutations in the MT2 gene may disrupt
the link between the body clock and insulin release, leading to
abnormal control of blood sugar.

Professor Philippe Froguel, from the School of Public Health at
Imperial College London, who led the study, said: "Blood sugar
control is one of the many processes regulated by the body's
biological clock. This study adds to our understanding of how
the gene that carries the blueprint for a key component in the
clock can influence people's risk of diabetes.

"We found very rare variants of the MT2 gene that have a much
larger effect than more common variants discovered before.
Although each mutation is rare, they are common in the sense
that everyone has a lot of very rare mutations in their DNA.
Cataloguing these mutations will enable us to much more
accurately assess a person's risk of disease based on their
genetics."

In the study, the Imperial team and their collaborators at
several institutions in the UK and France examined the MT2 gene
in 7,632 people to look for more unusual variants that have a
bigger effect on disease risk. They found 40 variants
associated with type 2 diabetes, four of which were very rare
and rendered the receptor completely incapable of responding to
melatonin. The scientists then confirmed the link with these
four variants in an additional sample of 11,854 people.

Professor Froguel and his team analysed each mutation by
testing what effect they have on the MT2 receptor in human
cells in the lab. The mutations that completely prevented the
receptor from working proved to have a very big effect on
diabetes risk, suggesting that there is a direct link between
MT2 and the disease.

###

The research was funded by the Wellcome Trust, the National
Institute for Health Research and the Medical Research Council
in the UK and the Agence National de la Recherche, the Contrat
de Projets Etat-R?gion Nord-Pas-De-Calais, the Soci?t?
Francophone du Diab?te, the Fondation Recherche M?dicale and
the Centre National de la Recherche Scientifique in France.

For further information please contact:

Sam Wong
Research Media Officer
Imperial College London
Email: sam.wong@imperial.ac.uk
Tel: +44(0)20 7594 2198
Out of hours duty press officer: +44(0)7803 886 248

Notes to editors:

1. Journal reference
A. Bonnefond et al. 'Rare MTNR1B variants impairing melatonin
receptor 1B function contribute to type 2 diabetes' Nature
Genetics, published online 29 January 2012.

2. About Imperial College London

Consistently rated amongst the world's best universities,
Imperial College London is a science-based institution with a
reputation for excellence in teaching and research that
attracts 14,000 students and 6,000 staff of the highest
international quality. Innovative research at the College
explores the interface between science, medicine, engineering
and business, delivering practical solutions that improve
quality of life and the environment - underpinned by a dynamic
enterprise culture.

Since its foundation in 1907, Imperial's contributions to
society have included the discovery of penicillin, the
development of holography and the foundations of fibre optics.
This commitment to the application of research for the benefit
of all continues today, with current focuses including
interdisciplinary collaborations to improve global health,
tackle climate change, develop sustainable sources of energy
and address security challenges.

In 2007, Imperial College London and Imperial College
Healthcare NHS Trust formed the UK's first Academic Health
Science Centre. This unique partnership aims to improve the
quality of life of patients and populations by taking new
discoveries and translating them into new therapies as quickly
as possible.

Website: http://www.imperial.ac.uk
Twitter: http://www.twitter.com/imperialspark
Podcast: http://www.imperial.ac.uk/media/podcasts

3. About the Medical Research Council

For almost 100 years the Medical Research Council has improved
the health of people in the UK and around the world by
supporting the highest quality science. The MRC invests in
world-class scientists. It has produced 29 Nobel Prize winners
and sustains a flourishing environment for internationally
recognised research. The MRC focuses on making an impact and
provides the financial muscle and scientific expertise behind
medical breakthroughs, including one of the first antibiotics
penicillin, the structure of DNA and the lethal link between
smoking and cancer. Today MRC funded scientists tackle research
into the major health challenges of the 21st century. http://www.mrc.ac.uk

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Body clock receptor linked to diabetes in new genetic study

Jobs, genetics won't stop her from climbing

On her last day as a public defender, Marybeth Dingledy didn't
talk about court cases.

She talked about an 18,491-foot volcano in Mexico. She talked
about seeing a climbing partner fall 100 feet during a descent
of Mount Baker, the first of many peaks Dingledy has scaled.

She talked about being dealt bad genetic cards, but taking
charge of her health as much as possible.

Oh, and there's that new job. She talked about that, too.

"I never thought it was my goal," Dingledy said Friday. "But my
dad reminded me at Thanksgiving that I had said, 'One day I'll
be a judge or a teacher.' "

After 16 years as an attorney with the Snohomish County Public
Defender Association, the 42-year-old Dingledy is scheduled to
be sworn in Feb. 7 as the county's newest Superior
Court judge. She was chosen by Gov. Chris Gregoire earlier
this month to fill the seat held by Judge Ronald Castleberry,
who is retiring.

Over coffee Friday, Dingledy said people in Snohomish County's
legal community suggested in recent years that she put her name
in the running for the bench. The Superior Court will soon have
two new faces. Former Snohomish County Prosecutor Janice
Ellis was selected in December to fill the seat held by
Judge Kenneth Cowsert, who also retired.

Dingledy said she was struck by "a whole lot of emotions" when
she was appointed to the bench. "I was incredibly excited and
honored, but also sad to be leaving a great job," she said.

Because of her judicial duties, Dingledy put a personal goal on
hold. This coming summer, she had planned to climb Alaska's
Mount McKinley, also known as Denali. The trip
would have taken her away for three weeks.

That wasn't practical while settling into her judicial role.
Also, Dingledy said, she may be in a campaign this summer and
fall if someone files for election to her seat on the bench.

Still, she plans a two-day climb of Mount Rainier this summer.

A mountain climber since 2006, Dingledy has raised money for
the Fred
Hutchinson Cancer Research Center through the
Climb to Fight Breast Cancer. She climbed Mount Baker in
2006 and Rainier in 2007. In 2008, Dingledy went to Mexico to
climb two inactive volcanoes, the 18,491-foot Pico de Orizaba and the
smaller Iztaccihuatl.

She traveled to Tanzania in 2009 to climb Mount Kilimanjaro. In
2010, a dangerous turn in the weather kept her group from
making it to the top of California's Mount Shasta. Last summer,
Dingledy climbed Mount
Olympus on the Olympic Peninsula.

"I've raised over $60,000" for the Hutchinson center, she said.

Those fundraising days are over. Dingledy said that as a judge,
it isn't appropriate to raise money, even for a cause as noble
as fighting breast cancer. Others are welcome to donate to the
effort that remains close to her heart.

For Dingledy, the battle against breast cancer is personal.

In 2003, she learned she inherited an altered BRCA2 gene. That
means she has a much higher than average chance of getting
breast cancer and ovarian cancer. Her father's mother died of
breast cancer, and two of her father's sisters developed the
disease.

According to the National
Cancer Institute, a gene on chromosome 13 normally helps
suppress cell growth. With a mutated BRCA1 or BRCA2 gene, there
is high risk of breast, ovarian or prostate cancer.

In October, Dingledy did something about it. Doctors had
recommended that her ovaries be removed by age 45. On Oct. 26,
she underwent a hysterectomy, which is removal of the uterus,
and removal of her ovaries.

The surgery, she said, cut her risk of breast cancer in half
and greatly reduced her risk of ovarian cancer. In a 2009
Herald interview, Dingledy said that without surgery she
would have at least an 80 percent lifetime risk of breast
cancer and a 20 percent chance of ovarian cancer.

"On the same day I scheduled the surgery, I signed up to climb
Denali," she said.

She won't get there this summer, but Dingledy is excited to
step up to the Superior Court.

As a public defender, she said, "I've become a really good
listener." She feels ready for the next step. Being a judge,
she said, requires listening, being respectful and
compassionate, figuring out the issues, and "trying to make
sure you are doing justice to everybody."

Denali can wait. Still, Dingledy isn't about to quit climbing,
even as her day job has her wearing a judge's robes.

She often trains by biking 16 miles to work from her Bothell
home, then taking a bus home. "I don't think any of the other
judges take a bike and the bus to work," she said.

Dingledy hasn't yet climbed up onto the bench, but she has
shown courage and fortitude climbing mountains and standing up
to health risks.

"I can't change my genes, but I'm not going to feel sorry for
myself," she said. "There's plenty to do."

Julie Muhlstein: 425-339-3460; muhlstein@heraldnet.com.

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Jobs, genetics won't stop her from climbing

Genetics study reveals how bacteria behind serious childhood disease evolve to evade vaccines

Public
release date: 29-Jan-2012
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Contact: Craig Brierley
c.brierley@wellcome.ac.uk
44-207-611-7329
Wellcome Trust

Genetics has provided surprising insights into why vaccines
used in both the UK and US to combat serious childhood
infections can eventually fail. The study, published today in
Nature Genetics, which investigates how bacteria change
their disguise to evade the vaccines, has implications for how
future vaccines can be made more effective.

Pneumococcus (Streptococcus pneumoniae) causes
potentially life-threatening diseases including pneumonia and
meningitis. Pneumococcal infections are thought to kill around
a million young children worldwide each year, though the
success of vaccination programmes has led to a dramatic fall in
the number of cases in countries such as the UK and US. These
vaccines recognise the bacteria by its polysaccharide, the
material found on the outside of the bacterial cell. There are
over ninety different kinds ? or 'serotypes' ? of the bacteria,
each with a different polysaccharide coating.

In 2000, the US introduced a pneumococcal vaccine which
targeted seven of the ninety serotypes. This '7-valent' vaccine
was extremely effective and had a dramatic effect on reducing
disease amongst the age groups targeted. Remarkably, the
vaccine has also prevented transmission from young children to
adults, resulting in tens of thousands fewer cases of
pneumococcal disease each year. The same vaccine was introduced
in the UK in 2006 and was similarly successful.

In spite of the success of the vaccine programmes, some
pneumococcal strains managed to continue to cause disease by
camouflaging themselves from the vaccine. In research funded by
the Wellcome Trust, scientists at the University of Oxford and
at the Centers for Disease Control and Prevention in Atlanta
studied what happened after the introduction of this vaccine in
the US. They used the latest genomic techniques combined with
epidemiology to understand how different serotypes of the
pneumococcus bacteria evolve to replace those targeted by the
initial vaccine.

The researchers found bacteria that had evaded the vaccine by
swapping the region of the genome responsible for making the
polysaccharide coating with the same region from a different
serotype, not targeted by the vaccine. This effectively
disguised the bacteria, making it invisible to the vaccine.
This exchange of genome regions occurred during a process known
as recombination, whereby one of the bacteria replaces a piece
of its own DNA with a piece from another bacterial type.

Dr Rory Bowden, from the University of Oxford, explains:
"Imagine that each strain of the pneumococcus bacteria is a
class of schoolchildren, all wearing the school uniform. If a
boy steals from his corner shop, a policeman ? in this case the
vaccine ? can easily identify which school he belongs to by
looking at his uniform. But if the boy swaps his sweater with a
friend from another school, the policemen will no longer be
able to recognise him and he can escape. This is how the
pneumococcus bacteria evade detection by the vaccine."

Dr Bowden and colleagues identified a number of recombined
serotypes that had managed to evade the vaccine. One in
particular grew in frequency and spread across the US from east
to west over several years. They also showed that during
recombination, the bacteria also traded a number of other parts
of the genome at the same time, a phenomenon never before
observed in natural populations of pneumococcus. This is of
particular concern as recombination involving multiple
fragments of DNA allows rapid simultaneous exchange of key
regions of the genome within the bug, potentially allowing it
to quickly develop antibiotic resistance.

The original 7-valent vaccine in the US has now been replaced
by a 13-valent vaccine, which targets thirteen different
serotypes, including the particular type which had escaped the
original vaccine. In the UK, the 7-valent vaccine resulted in a
substantial drop in disease overall. This overall effect was a
mixture of a large drop in frequency of the serotypes targeted
by the vaccine with some growth in serotypes not targeted by
the vaccine. The 13-valent vaccine was introduced in the UK in
2010.

Derrick Crook, Professor of Microbiology at the University of
Oxford and Infection Control Doctor at the Oxford University
Hospitals NHS Trust, adds: "Childhood vaccines are very
effective at reducing disease and death at a stage in our lives
when we are susceptible to serious infections. Understanding
what makes a vaccine successful and what can cause it to fail
is important. We should now be able to understand better what
happens when a pneumococcal vaccine is introduced into a new
population. Our work suggests that current strategies for
developing new vaccines are largely effective but may not have
long term effects that are as successful as hoped."

Dr Bernard Beall, a scientist at the Centers for Disease
Control and Prevention commented: "The current vaccine strategy
of targeting predominant pneumococcal serotypes is extremely
effective, however our observations indicate that the organism
will continue to adapt to this strategy with some measurable
success."

The Wellcome Trust, which part-funded this research, views
combating infectious disease and maximising the health benefits
of genetic research as two of its strategic priorities. Dr
Michael Dunn, Head of Molecular and Physiological Sciences at
the Wellcome Trust commented: "New technologies allow us to
rapidly sequence disease-causing organisms and see how they
evolve. Coupled with collaborations with epidemiologists, we
can then track how they spread and monitor the potential impact
this will have on vaccine efficiency. This will provide useful
lessons for vaccine implementation strategies."

###

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Genetics study reveals how bacteria behind serious childhood disease evolve to evade vaccines

Gene bank rehab gets P5 M

By MARVYN N. BENANING

MANILA, Philippines — The National Plant Genetics Resources
Laboratory (NPGRL) at the University of the Philippines at Los
Baños (UPLB) is undergoing a P5-million upgrading by the
Department of Agriculture (DA).

NPGRL is the country’s principal repository of genetic
resources for crops crucial to agriculture and food security.

Located at the Institute of Plant Breeding, College of
Agriculture (IPB-CA) of UPLB, the project is scheduled to be
completed by April.

Agriculture Assistant Scretary and National Rice Program
Cordinator Dante S. Delima said the project involves the repair
of facilities and equipment for seed processing
characterization and NPGRL in vitro units.

“NPGRL is at the forefront of plant genetic resources
management and conservation,” Delima said, “and repairs are
necessary to ensure the smooth flow of operations at the
laboratory which was damaged by a strong typhoon a few years
ago,” Delima said.

Project leader Visitacion Huelgas thanked DA for the support
and vowed to complete the repair, rehabilitation, electrical
work and purchase of needed equipment by April.

UPLB Vice Chancellor for Research and Extension Ma. Victoria
Espaldon, UPLB Dean Domingo Angeles, and Director Jose
Hernandez also signed the letter.

Agriculture Secretary Proceso J. Alcala initiated the project
to upgrade research stations, stock farms, and experimental
stations in the countryside for possible funding.

“Ito ang magiging mukha ng ating kagawaran sa bawa’t lugar.
Ayusin natin ito at gawing sentro ng teknolohiya na ipamamahagi
sa mga magsasaka,” Alcala said.

The NPGRL is the national leader in plant genetic resource
activities. It identifies important and potentially useful
agricultural crops used by plant breeders and other researchers
in their crop improvement and breeding activities.

NPGRL holds the largest national germplasm collection in
Southeast Asia, comprised of more than 45,000 accessions of 600
agricultural crop species and their relatives such as corn,
mungbean, tomato, eggplant, yardlong bean, cowpea, and edible
and wild Musa, which includes banana and plantain, mongo and
root crops.

It also conducts research on the conservation and sustainable
use of agricultural biodiversity.

NPGRL also introduced and evaluated improved and superior
landraces of banana and identified cultivars that have good
potential in terms of yield and acceptability.

It was also identified as National Repository, Multiplication
and Distribution Center by Bioversity International, an
international non-profit organization that undertakes research
aimed at improving people’s lives through the use and
conservation of agricultural biodiversity.

Go here to read the rest:
Gene bank rehab gets P5 M

Genetic abnormalities may cause cerebral palsy, study suggests

ScienceDaily (Jan. 26, 2012) — For
years it was thought that a difficult birth and other perinatal
factors were the leading causes of cerebral palsy (CP), a group
of disorders that can involve brain and nervous system
functions such as movement, learning, hearing, seeing and
thinking. Now, researchers at Geisinger Health System find that
the majority of cerebral palsy causes may in fact be caused by
genetic abnormalities.

Published in the The Lancet Neurology, Geisinger
researchers find that CP -- the most common physical disability
of childhood -- is probably caused by multiple genetic factors,
similar to other neurodevelopmental disorders such as autism
and intellectual disability. The paper suggests physicians
should consider performing genetic testing when children
present with CP and CP-like conditions.

"There is a widespread misconception that most cases of CP are
caused by difficult delivery leading to birth asphyxia," said
Andres Moreno De Luca, M.D., research scientist at the Genomic
Medicine Institute, Geisinger Health System, and lead author of
the paper. "What we're finding is a growing body of evidence
that suggests mutations in multiple genes are responsible for
CP. In fact, we suspect these genetic abnormalities may also be
the cause of some difficult births to begin with."

Despite substantial improvements in obstetric and neonatal
care, the paper finds the worldwide prevalence of cerebral
palsy has remained stable at 2 to 3 per 1,000 livebirths for
more than 40 years. Inadequate oxygen supply to fetuses, known
as birth asphyxia, remains the most studied factor associated
with CP, though electronic fetal monitoring and other
technologies have been developed to detect fetal distress.

"What we're finding is even though more preventative efforts
have been put in place, like fetal monitoring, the incidence of
CP has not decreased," said David Ledbetter, Ph.D., chief
scientific officer, Geisinger Health System. "We've seen a
five-fold increase in the rate of caesarean sections, which are
done in part to avoid potentially difficult delivery, and
again, the CP rates remain steady. These findings lead us to
believe genetics play a much bigger role than previously
thought."

The paper also reports that even though most cases of CP are
not caused by birth asphyxia and those that are can rarely be
prevented by obstetric intervention, between 1999 and 2003 an
estimated 76 percent of obstetricians in the U.S. faced medical
malpractice litigation, most often for alleged birth
mismanagement resulting in CP.

"We now know of six genes that can cause CP when disrupted, and
we estimate that many other developmental brain genes probably
contribute to the genetic heterogeneity of this disorder," said
Dr. Moreno De Luca. "Many capable obstetricians face legal
action even though research is telling us genetics is the
likely cause of most cases of CP."

As the paradigm shift continues and more researchers,
clinicians, and the general population start to consider the
cerebral palsies as a group of neurogenetic disorders, the
paper states we will probably witness an increase in research
efforts, a change in the diagnostic approach, and eventually
novel therapies for treating CP.

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Story Source:

The above story is reprinted[1] from
materials[2] provided
by Geisinger Health System[3], via
Newswise[4].

Note: Materials may be edited for content and length. For
further information, please contact the source cited
above.


Journal Reference:

  1. Andres Moreno-De-Luca, David H Ledbetter, Christa L Martin.
    Genomic insights into the causes and classification of
    the cerebral palsies
    . The Lancet Neurology,
    2012; DOI: 10.1016/S1474-4422(11)70287-3[5]

Note: If no author is given, the source is cited
instead.

Disclaimer: This article is not intended
to provide medical advice, diagnosis or treatment. Views
expressed here do not necessarily reflect those of ScienceDaily
or its staff.

References

  1. ^ reprinted
    (webapps.geisinger.org)
  2. ^ materials
    (www.newswise.com)
  3. ^ Geisinger Health System
    (www.geisinger.org)
  4. ^ Newswise
    (www.newswise.com)
  5. ^ 10.1016/S1474-4422(11)70287-3
    (dx.doi.org)

Read more from the original source:
Genetic abnormalities may cause cerebral palsy, study suggests

Genetic variation that raises risk of serious complication linked to osteoporosis drugs identified

ScienceDaily (Jan. 27, 2012) — New
York, NY (January 26, 2012) — Researchers at the Columbia
University College of Dental Medicine have identified a genetic
variation that raises the risk of developing serious necrotic
jaw bone lesions in patients who take bisphosphonates, a common
class of osteoclastic inhibitors. The discovery paves the way
for a genetic screening test to determine who can safely take
these drugs. The study appears in the online version of the
journal The Oncologist.

Oral bisphosphonates are currently taken by some 3 million
women in the United States for the prevention or treatment of
osteoporosis. In addition, intravenous bisphosphonates are
given to thousands of cancer patients each year to control the
spread of bone cancer and prevent excess calcium
(hypercalcemia) from accumulating in the blood. Bisphosphonates
work by binding to calcium in the bone and inhibiting
osteoclasts, bone cells that break down the bone’s mineral
structure.

“These drugs have been widely used for years and are generally
considered safe and effective,” said study leader Athanasios I.
Zavras, DMD, MS, DMSc, associate professor of Dentistry and
Epidemiology and Director of the Division of Oral Epidemiology
& Biostatistics at the Columbia University College of
Dental Medicine. “But the popular literature and blogs are
filled with stories of patients on prolonged bisphosphonate
therapy who were trying to control osteoporosis or
hypercalcemia only to develop osteonecrosis of the jaw.”

Osteonecrosis of the jaw, or ONJ, often leads to painful and
hard-to-treat bone lesions, which can eventually lead to loss
of the entire jaw. Among people taking bisphosphonates, ONJ
tends to occur in those with dental disease or those who
undergo invasive dental procedures.

There are no reliable figures on the incidence of ONJ in
patients taking oral bisphosphonates. Estimates range from 1 in
1,000 to 1 in 100,000 patients for each year of exposure to the
medication, according to the American College of Rheumatology.
ONJ is more common among cancer patients taking the intravenous
form of the drug, affecting about 5 to 10 percent of these
individuals, noted Dr. Zavras.

Studies have suggested that genetic factors play a major role
in predisposing patients to ONJ.
Delving deeper into this question, Dr. Zavras and his
colleagues performed genome-wide analyses of 30 patients who
were taking bisphosphonates and had developed ONJ and compared
them with several bisphosphonate users who were disease free.

The researchers found that patients who had a small variation
in the RBMS3 gene were 5.8 times more likely to develop ONJ
than those without the variation. The study also identified
small variations in two other genes, IGFBP7 and ABCC4, that may
contribute to ONJ risk.

“Our ultimate goal is to develop a pharmacogenetic test that
personalizes risk assessment for ONJ, a test that you could
give to people before they start to use bisphosphonates,” said
Dr. Zavras. “Those who are positive for this genetic variation
would select some other treatment, while those who are negative
could take these medications with little fear of developing
ONJ.”

“At the moment, many women discontinue or avoid treatment for
serious osteoporosis because they are afraid of losing their
jaw bones,” added Dr. Zavras. “There even are reports of
dentists who have refused to perform certain invasive
procedures in patients taking bisphosphonates. So there is a
great need for a pharmacogenetic screening test to determine
which patients are really at risk for ONJ.”

The current study looked only at Caucasians. Further studies
are needed to determine whether the RBMS3 gene variation is
seen in other racial groups, according to the researchers.

The paper is entitled, “Genome-wide pharmacogenetics of
bisphosphonate-induced osteonecrosis of the jaw: the role of
RBMS3.” The lead authors are Paola Nicoletti of CUMC and
Vassiliki M. Cartsos of Tufts School of Dental Medicine. The
other contributors are Penelope K. Palaska of Tufts and Yufeng
Shen and Aris Floratos at the Columbia University Medical
Center Bioinformatics Department.

This research was supported by grant number 7R21DE018143-03
from the National Institute of Dental and Craniofacial
Research.
Columbia University has filed a patent application with the
United States Patent and Trademark Office relating to a genetic
screening test for predisposition to ONJ, and, through its
technology transfer office, Columbia Technology Ventures, is
actively seeking partners to collaborate, license and
commercialize the technology.
-####-

Columbia University College of Dental Medicine (CDM) was
established in 1916 as the School of Dental and Oral Surgery,
when the School became incorporated into Columbia University.
The College’s mission has evolved into a tripartite commitment
to education, patient care, and research. The mission of the
College of Dental Medicine is totrain general dentists, dental
specialists, and dental assistants in a setting that emphasizes
comprehensive dental care delivery and stimulates professional
growth; inspire, support, and promote faculty, pre- and
postdoctoral student, and hospital resident participation in
research to advance the professional knowledge base; and
provide comprehensive dental care for the underserved community
of northern Manhattan. For more information, please visit:
http://dental.columbia.edu/[1]

Columbia University Medical Center provides international
leadership in basic, pre-clinical and clinical research, in
medical and health sciences education, and in patient care. The
medical center trains future leaders and includes the dedicated
work of many physicians, scientists, public health
professionals, dentists, and nurses at the College of
Physicians and Surgeons, the Mailman School of Public Health,
the College of Dental Medicine, the School of Nursing, the
biomedical departments of the Graduate School of Arts and
Sciences, and allied research centers and institutions.
Established in 1767, Columbia's College of Physicians and
Surgeons was the first institution in the country to grant the
M.D. degree and is among the most selective medical schools in
the country. Columbia University Medical Center is home to the
largest medical research enterprise in New York City and State
and one of the largest in the United States.

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The above story is reprinted from materials[2] provided
by Columbia
University Medical Center
[3], via
Newswise[4].

Note: Materials may be edited for content and length. For
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above.


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to provide medical advice, diagnosis or treatment. Views
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References

  1. ^ http://dental.columbia.edu/
    (dental.columbia.edu)
  2. ^ materials
    (www.newswise.com)
  3. ^ Columbia University Medical
    Center
    (www.cumc.columbia.edu)
  4. ^ Newswise
    (www.newswise.com)

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