Elusive platelet count and limb development gene discovered
Posted: February 27, 2012 at 1:11 am
Public release date: 26-Feb-2012
[ | E-mail | Share ]
Contact: Aileen Sheehy
press.office@sanger.ac.uk
44-122-349-6928
Wellcome Trust Sanger Institute
Researchers have identified an elusive gene responsible for Thrombocytopenia with Absent Radii (TAR), a rare inherited blood and skeletal disorder. As a result, this research is now being transformed into a medical test that allows prenatal diagnosis and genetic counselling in affected families.
The team used genetic sequencing to discover that TAR results from low levels of the protein called Y14. They found that the syndrome occurs by a unique inherited mechanism.
Platelets are the second most abundant cell in the blood. Their main task is to survey the blood vessel wall for damage and to plug and repair it where required. Some people are born with low numbers of platelets and these rare conditions are thought to be inherited. TAR syndrome combines the unique features of low platelet count and prominent bleeding, especially in infancy, and skeletal abnormalities affecting the upper limb ranging from absence of the radial bone in the forearm to virtually total absence of upper limb. The genetic basis of TAR syndrome has eluded researchers for 50 years.
"Without the use of modern genomics technologies, the discovery of this unexpected mechanism of disease inheritance would have been much more difficult", said Dr Cornelis Albers, from the Sanger Institute and the University of Cambridge. "To achieve our latest findings, we deciphered about 40 million letters of genetic code in five patients."
Many people with TAR were known to have a deletion in one copy of chromosome 1, but this was thought not to be the whole story because parents who carry the same deletion are not suffering from TAR: other variants had to be involved. The team sequenced the genomes of people affected by the disorder who also carried the deletion and discovered that the vast majority of them had one of two variants of a gene called RBM8A. They found that when the genetic deletion and one of the variants are co-inherited by a child, TAR results.
RBM8A controls the production of the protein Y14. They found that the combination of the genetic deletion of one copy of the RBM8A gene and the variants on the other copy greatly reduces the level of Y14. The team concluded that it is low levels of Y14 that affect platelet formation and cause TAR disorder.
"The lack of production of adequate amounts of the protein Y14 in TAR patients only seems to effect the formation of platelets but not of other blood cells." said Dr Cedric Ghevaert from the University of Cambridge. "We have shed some light on how some inherited disorders can present with such striking features associating seemingly unconnected characteristics such as skeletal and blood defects"
This is the first human disorder identified to be caused by a presumed defect of the Exon Junction Complex, part of the cellular machinery that contributes to producing messages that direct protein production. This study opens the path that could lead to the identification of the genetic basis of other similar inherited syndromes, which will help improvements in diagnosis, genetic counselling and patient care in the NHS and beyond.
"The discovery of the gene for TAR will make it simpler to diagnose more accurately future cases with a simple DNA test. This new test is currently being developed for the NHS as part of the international ThromboGenomics initiative led by Professor Ouwehand" commented Dr Ruth Newbury-Ecob, Honorary Reader in Medical Genetics and Consultant in Clinical Genetics at the University of Bristol Hospitals.
###
Notes to Editors
The findings were made following a collaborative study by the NHS Blood and Transplant platelet research team at the University of Cambridge and the Wellcome Trust Sanger Institute, which is led by Dr Cedric Ghevaert and Professor Willem Ouwehand. The Cambridge researchers joined forces with Dr Ruth Newbury-Ecob from the University of Bristol and worked together with various other European research partners from Belgium, France, Germany and the Netherlands.
Publication
Nature Genetics website, 26 February 2012
Albers et al 'Compound inheritance of a low-frequency regulatory SNP and a rare null mutation in exon-junction complex subunit RBM8A causes TAR syndrome' DOI 10.1038/ng.1083
Funding
The platelet research team in Cambridge is supported by the British Heart Foundation, the European Commission, the National Institute for Health Research for England (NIHR), NHS Blood and Transplant and the Wellcome Trust.
Dr Cedric Ghevaert and Prof Willem Ouwehand are also consultant Haematologists for NHS Blood and Transplant (NHSBT). NHSBT collects blood and platelets from non-remunerated volunteer donors. Every day about 8,000 units of blood are needed by the NHS and 1100 platelet concentrates. For the latter about 600 donors attend a special clinic at which platelets are harvested from the blood of the donor by a process called apheresis.
The National Institute for Health Research (NIHR) http://www.nihr.ac.uk) is the major governmental fund provider for clinical translational research in the NHS. The mission of the NIHR is to maintain a health research system in which the NHS supports outstanding individuals, working in world-class facilities, conducting leading-edge research, focussed on the needs of patients and the public.
The Wellcome Trust is a global charity dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust's breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests. http://www.wellcome.ac.uk
The Wellcome Trust Sanger Institute, which receives the majority of its funding from the Wellcome Trust, was founded in 1992. The Institute is responsible for the completion of the sequence of approximately one-third of the human genome as well as genomes of model organisms and more than 90 pathogen genomes. In October 2006, new funding was awarded by the Wellcome Trust to exploit the wealth of genome data now available to answer important questions about health and disease. http://www.sanger.ac.uk
[ | E-mail | Share ]
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.
See the rest here:
Elusive platelet count and limb development gene discovered
- Gene Therapy Could Prevent Blindness [Last Updated On: June 10th, 2010] [Originally Added On: June 10th, 2010]
- Gene Brodland Sits with Cambridge Who's Who in a Revealing Interview [Last Updated On: June 16th, 2010] [Originally Added On: June 16th, 2010]
- Researchers Make Colon Cancer Breakthrough [Last Updated On: July 20th, 2010] [Originally Added On: July 20th, 2010]
- Pro abortion- Antiabortion myth8 - Fly to India for safe abortion! [Last Updated On: October 16th, 2010] [Originally Added On: October 16th, 2010]
- New Fertility Test / Whooping Cough Alert / Gene Therapy for Depression [Last Updated On: October 21st, 2010] [Originally Added On: October 21st, 2010]
- Alzheimer's Breakthrough? [Last Updated On: October 23rd, 2010] [Originally Added On: October 23rd, 2010]
- Audio Genetics Lab - Native Flute - MP3Tera Forums [Last Updated On: December 8th, 2010] [Originally Added On: December 8th, 2010]
- Gene Therapy - Cortical Studios [Last Updated On: May 8th, 2011] [Originally Added On: May 8th, 2011]
- There Shall Be Physicians for the Spirit: USC Institute for Genetic Medicine Art Gallery [Last Updated On: May 8th, 2011] [Originally Added On: May 8th, 2011]
- IRRI: Rice genetic diversity and discovery [Last Updated On: May 8th, 2011] [Originally Added On: May 8th, 2011]
- Research Symposium: Mork Depart - 2006 - Video 1 [Last Updated On: May 8th, 2011] [Originally Added On: May 8th, 2011]
- Mendelian Genetics [Last Updated On: May 8th, 2011] [Originally Added On: May 8th, 2011]
- Ayurveda [Last Updated On: May 8th, 2011] [Originally Added On: May 8th, 2011]
- Drs. Kaspar and MacKenzie discuss the promise and path forward for SMA Gene Therapy [Last Updated On: May 8th, 2011] [Originally Added On: May 8th, 2011]
- 3. Genetic Engineering [Last Updated On: May 8th, 2011] [Originally Added On: May 8th, 2011]
- Prof. Martinez Cruzado Lecture Part 3 "Amerindian Gene Study In Puerto Rico" [Last Updated On: May 8th, 2011] [Originally Added On: May 8th, 2011]
- Gene Therapy Research Makes Nationwide Children's Worthy of Wellstone Center [Last Updated On: May 8th, 2011] [Originally Added On: May 8th, 2011]
- Gene Therapy Example [Last Updated On: May 9th, 2011] [Originally Added On: May 9th, 2011]
- Sweet Tooth Gene [Last Updated On: May 9th, 2011] [Originally Added On: May 9th, 2011]
- OHSU's video of new gene therapy method developed at the Oregon National Primate Research Center [Last Updated On: May 9th, 2011] [Originally Added On: May 9th, 2011]
- Gregor Mendel's Punnett Squares [Last Updated On: May 9th, 2011] [Originally Added On: May 9th, 2011]
- Ethical Concerns With Genetic Engineering [Last Updated On: May 9th, 2011] [Originally Added On: May 9th, 2011]
- Dr. Laura Niklason on the importance of her AFAR grants for telomerase gene therapy research [Last Updated On: May 9th, 2011] [Originally Added On: May 9th, 2011]
- What is the future of genetic medicine? [Last Updated On: May 9th, 2011] [Originally Added On: May 9th, 2011]
- Prof. Martinez Cruzado Lecture Part 2 "Amerindian Gene Study In Puerto Rico" [Last Updated On: May 9th, 2011] [Originally Added On: May 9th, 2011]
- Jewish DNA - Genetic Research and The Origins of the Jewish People [Last Updated On: May 9th, 2011] [Originally Added On: May 9th, 2011]
- Future of genetic engineering - by Futurist Dr Patrick Dixon. Genetic mutations and genetic disorders. Gene science by conference keynote speaker [Last Updated On: May 11th, 2011] [Originally Added On: May 11th, 2011]
- annstewart82's Genetic Medicine and God [Last Updated On: May 13th, 2011] [Originally Added On: May 13th, 2011]
- Genetic research could unlock breeding seasons in sheep [Last Updated On: May 13th, 2011] [Originally Added On: May 13th, 2011]
- Genetics 101 Part 1: What are genes? [Last Updated On: May 13th, 2011] [Originally Added On: May 13th, 2011]
- Molecular and Cellular Foundations of Medicine, 1 of 2 [Last Updated On: May 13th, 2011] [Originally Added On: May 13th, 2011]
- Dan Arking of Johns Hopkins Medicine [Last Updated On: May 17th, 2011] [Originally Added On: May 17th, 2011]
- Genetics : How Is Gene Therapy Done? [Last Updated On: May 19th, 2011] [Originally Added On: May 19th, 2011]
- Gene Therapy Shows Promise for Blindness [Last Updated On: May 19th, 2011] [Originally Added On: May 19th, 2011]
- Tomato suicide gene therapy [Last Updated On: May 19th, 2011] [Originally Added On: May 19th, 2011]
- Cancer Alternative Treatment - Gene Therapy for Cancer a Report from Channel 4 News [Last Updated On: May 19th, 2011] [Originally Added On: May 19th, 2011]
- Muscular Dystrophy Gene Therapy: ScienCentral News Video [Last Updated On: May 19th, 2011] [Originally Added On: May 19th, 2011]
- Sickle Cell Anemia -- Hope from Gene Therapy [Last Updated On: May 19th, 2011] [Originally Added On: May 19th, 2011]
- Challenges of gene therapy [Last Updated On: May 19th, 2011] [Originally Added On: May 19th, 2011]
- Pain Gene Therapy [Last Updated On: May 19th, 2011] [Originally Added On: May 19th, 2011]
- Gene therapy success 'reverses' blindness [Last Updated On: May 19th, 2011] [Originally Added On: May 19th, 2011]
- DNA Gene Therapy [Last Updated On: May 19th, 2011] [Originally Added On: May 19th, 2011]
- The Neural Circuitry of Perception [Last Updated On: May 19th, 2011] [Originally Added On: May 19th, 2011]
- Resetting Metabolism- Nuclear Receptors and AMPK: A Lecture by Ronald Evans, PhD [Last Updated On: May 19th, 2011] [Originally Added On: May 19th, 2011]
- Islands at Risk (Part 2) - Genetic Engineering in Hawai'i [Last Updated On: May 19th, 2011] [Originally Added On: May 19th, 2011]
- Gene Therapy journal videocast from ASGCT 2011 Xiao Xiao on gene therapy for muscular dystrophy [Last Updated On: May 20th, 2011] [Originally Added On: May 20th, 2011]
- HYBRID HUMANS-Hair Follicle Gene Therapy [Last Updated On: May 20th, 2011] [Originally Added On: May 20th, 2011]
- Genetics 101 Part 4: What is phenotype? [Last Updated On: May 20th, 2011] [Originally Added On: May 20th, 2011]
- Lloyd Pye - Ancient Genetic Engineering [Last Updated On: May 20th, 2011] [Originally Added On: May 20th, 2011]
- Study Designs: Genetic Association Studies [Last Updated On: May 20th, 2011] [Originally Added On: May 20th, 2011]
- Gene Therapy for Genetic Disease: The Long and Winding Road [Last Updated On: May 20th, 2011] [Originally Added On: May 20th, 2011]
- Introduction to Population Genetics [Last Updated On: May 20th, 2011] [Originally Added On: May 20th, 2011]
- Islands at Risk (Part 1) - Genetic Engineering in Hawai'i [Last Updated On: May 20th, 2011] [Originally Added On: May 20th, 2011]
- Genetics Based Research on Treatment-Resistant Epilepsy [Last Updated On: May 20th, 2011] [Originally Added On: May 20th, 2011]
- Science in Action: Gene Therapy for Color Blindness [Last Updated On: May 21st, 2011] [Originally Added On: May 21st, 2011]
- Gregg Semenza of Johns Hopkins Medicine on HIF 1 [Last Updated On: May 21st, 2011] [Originally Added On: May 21st, 2011]
- The Sleepiness Gene [Last Updated On: May 21st, 2011] [Originally Added On: May 21st, 2011]
- Blind Gene Therapy [Last Updated On: May 21st, 2011] [Originally Added On: May 21st, 2011]
- Richard Dawkins and Dr Yan on genetic ancestry (extended version) - Bang Goes the Theory - BBC One [Last Updated On: May 22nd, 2011] [Originally Added On: May 22nd, 2011]
- Joshua Mendell of Johns Hopkins Medicine [Last Updated On: May 22nd, 2011] [Originally Added On: May 22nd, 2011]
- Genetic/Genomic Faculty Champion Initiative (PM session) [Last Updated On: May 22nd, 2011] [Originally Added On: May 22nd, 2011]
- euronews science - Epigenetics [Last Updated On: May 22nd, 2011] [Originally Added On: May 22nd, 2011]
- The Genetic Age, Panel 1 [Last Updated On: May 22nd, 2011] [Originally Added On: May 22nd, 2011]
- Biobanking and Bioethics: When Genetics Research Hits the Courts [Last Updated On: May 22nd, 2011] [Originally Added On: May 22nd, 2011]
- Gene Therapy journal videocast from ASGCT 2011 Darren Wolfe on gene therapy for pain.m4v [Last Updated On: May 23rd, 2011] [Originally Added On: May 23rd, 2011]
- Genetics 101 Part 3: Where do your genes come from? [Last Updated On: May 23rd, 2011] [Originally Added On: May 23rd, 2011]
- ASHG 2010 Mtg.: "Complex Disease Genetics Research in Populations" (Dr. Carlos Bustamente) [Last Updated On: May 23rd, 2011] [Originally Added On: May 23rd, 2011]
- Public Talk - Prof Leonard Seymour, Oxford [Last Updated On: May 23rd, 2011] [Originally Added On: May 23rd, 2011]
- A New Era in Medicine: Genetics [Last Updated On: May 23rd, 2011] [Originally Added On: May 23rd, 2011]
- Genetic Engineering Animation [Last Updated On: May 23rd, 2011] [Originally Added On: May 23rd, 2011]
- Linda Brzustowicz - Genetic Causes of Schizophrenia [Last Updated On: May 23rd, 2011] [Originally Added On: May 23rd, 2011]
- Hadassah Gene Therapy Center [Last Updated On: May 23rd, 2011] [Originally Added On: May 23rd, 2011]
- Gene Therapy journal videocast from ASGCT 2011 Robin Ali on gene therapy for retinal disease [Last Updated On: May 23rd, 2011] [Originally Added On: May 23rd, 2011]
- UF cardiologists study gene-modified stem cells to help Dobermans with common heart condition [Last Updated On: May 23rd, 2011] [Originally Added On: May 23rd, 2011]
- Akhilesh Pandey of Johns Hopkins Medicine [Last Updated On: May 23rd, 2011] [Originally Added On: May 23rd, 2011]
- China's Cancer Drug - China [Last Updated On: May 23rd, 2011] [Originally Added On: May 23rd, 2011]
- Genetic Therapy Restored Boy's Sight [Last Updated On: May 24th, 2011] [Originally Added On: May 24th, 2011]
- Molecular and Cellular Foundations of Medicine Class, 2 of 2 [Last Updated On: May 24th, 2011] [Originally Added On: May 24th, 2011]
- Talking Research - Professor George Ebers - Vitamin D and genetics in MS [Last Updated On: May 24th, 2011] [Originally Added On: May 24th, 2011]
- Designing Humanity - Genetic Engineering [Last Updated On: May 30th, 2011] [Originally Added On: May 30th, 2011]