Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Extra Chromosome 21 Removed from Down Syndrome Cell Line

Published: Monday, November 12, 2012
Last Updated: Monday, November 12, 2012
Bookmark and Share
Scientists have succeeded in removing the extra copy of chromosome 21 in cell cultures derived from a person with Down syndrome, a condition in which the body’s cells contain three copies of chromosome 21.

A triplicate of any chromosome is a serious genetic abnormality called a trisomy. Trisomies account for almost one-quarter of pregnancy loss from spontaneous miscarriages, according to the research team. Besides Down syndrome (trisomy 21), some other human trisomies are extra Y or X chromosomes, and Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13), both of which have extremely high newborn fatality rates.

In their report appearing in the Nov. 2 edition of Cell Stem Cell, a team led by Dr. Li B. Li of the UW Department of Medicine described how they corrected trisomy 21 in human cell lines they grew in the lab.  The senior scientists on the project were gene therapy researchers Dr. David W. Russell, professor of medicine and biochemistry, and Dr. Thalia Papayannopoulou, professor of medicine.

The targeted removal of a human trisomy, they noted, could have both clinical and research applications.

In live births, Down syndrome is the most frequent trisomy. The condition has characteristic eye, facial and hand features, and can cause many medical problems, including heart defects, impaired intellect, premature aging and dementia, and certain forms of leukemia, a type of blood cancer.

“We are certainly not proposing that the method we describe would lead to a treatment for Down syndrome,” Russell said.  “What we are looking at is the possibility that medical scientists could create cell therapies for some of the blood-forming disorders that accompany Down syndrome.”

For example, he said, someday Down syndrome leukemia patients might have stem cells derived their own cells, and have the trisomy corrected in these lab-cultured cells.  They could then receive a transplant of their own stem cells – minus the extra chromosome – or healthy blood cells created from their fixed stem cells and that therefore don’t promote leukemia, as part of their cancer care.

He added that the ability to generate stem cells with and without trisomy 21 from the same person could lead to better understanding of how problems tied to Down syndrome originate.  The cell lines would be genetically identical, except for the extra chromosome. Researcher could contrast, for example how the two cell lines formed brain nerve cells, to learn the effects of trisomy 21 on neuron development, which might offer insights into the lifelong cognitive impairments and adulthood mental decline of Down syndrome. Similar comparative approaches could seek the underpinnings of untimely aging or defective heart tissue in this genetic condition.

The formation of trisomies is also a problem in regenerative medicine research using stem cells. Russell and his team observed that their approach could also be used to revert the unwanted trisomies that often arise in creating stem cell cultures.

Figuring out the exact techniques for removing the extra chromosome was tricky, Russell said, but his colleague Li worked hard to solve several challenges during his first attempts at deriving the engineered cell lines.

“Dr. Li’s achievement was a tour de force,” Russell said.

The researchers used an adeno-associated virus as a vehicle to deliver a foreign gene called TKNEO into a particular spot on chromosome 21, precisely within a gene called APP, which sits on the long arm of the chromosome.  The TKNEO transgene was chosen because of its predicted response to positive and negative selection in specific laboratory growth mediums.  When grown in conditions that selected against TKNEO, the most common reason for cells to survive was the spontaneous loss of the chromosome 21 harboring the transferred gene. Other survival tactics were point mutations, which are single, tiny alterations in DNA base pairs; gene silencing, which meant TKNEO was “turned off” by the cell; or deletion of the TKNEO.

Russell explained a key advantage of this technique for getting rid of the entire extra chromosome: Once it was gone, nothing was left behind.

“Gene therapy researchers have to be careful that their approaches do not cause gene toxicity,” he said. This means, for example, that removal of a chromosome must not break or rearrange the remaining genetic code. This method shouldn’t do that.”


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,000+ scientific posters on ePosters
  • More Than 4,400+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Immune Booster Tested in Advanced Merkel Cell Cancer
The immunotherapy drug produced durable responses in many patients.
Thursday, April 21, 2016
Pandemic E. coli Strain Cloaks its Stealth Strategies
Antibiotic resistance and weakened immunity only partially explain persistent, harmful infection.
Wednesday, April 20, 2016
Oral Swabs for TB Diagnosis
Bill & Melinda Gates Foundation grant to UW supports project conducted in partnership with South African team.
Thursday, April 07, 2016
Conflicting Views on Breast Biopsies
Initial indications of atypia and ductal carcinoma in situ are prone to disagreement among pathologists.
Wednesday, March 23, 2016
TAxI Shuttles Protein Cargo into Spinal Cord
A small peptide, TAxI, holds hope for administering treatments for motor neuron disorders via a muscle injection.
Wednesday, February 17, 2016
Neanderthal DNA Influences Human Disease Risk
Large-scale, evolutionary analysis compares genetic data alongside electronic health records.
Friday, February 12, 2016
Mitochondrial Troublemakers Unmasked in Lupus
Drivers of autoimmune disease inflammation discovered in the traps of pathogen-capturing white blood cells.
Monday, January 25, 2016
Draining Speeds up Bioassays
New methodology means biological assays that once took hours could instead take minutes.
Thursday, January 14, 2016
Progress Toward Creating Broad-Spectrum Antiviral
UW researchers working in collaboration with Kineta Inc. and the University of Texas at Galveston have shown that making a drug-like molecule to turn on innate immunity can induce genes to control infection in several -known viruses.
Monday, December 21, 2015
Compound Found to Trigger Innate Immunity Against Viruses
Success at inducing gene action to suppress Ebola, West Nile and other RNA viruses.
Monday, December 21, 2015
Big Moves in Protein Structure Prediction and Design
Custom design with atomic level accuracy enables researchers to craft a whole new world of proteins.
Friday, December 18, 2015
$12-Million Awarded to Study the Human Genome in 4-D
Project seeks to understand how a 6.5 feet of DNA folds to fit inside a cell.
Tuesday, October 20, 2015
First Results Describing Sick Sea Star Immune Response
Though millions of sea stars along the West Coast have perished in the past several years from an apparent wasting disease, scientists still don’t know why.
Monday, October 12, 2015
Editing Genes to Create HIV Killers
Seattle scientists have managed to genetically transform human cells in the lab from HIV targets to HIV killers, and the technique could have implications for cancer and other diseases.
Monday, October 05, 2015
A New Single-Molecule Tool to Observe Enzymes at Work
A team of scientists at the University of Washington and the biotechnology company Illumina have created an innovative tool to directly detect the delicate, single-molecule interactions between DNA and enzymatic proteins.
Wednesday, September 30, 2015
Scientific News
Releasing Cancer Cells for Better Analysis
A new device developed at the University of Michigan could provide a non-invasive way to monitor the progress of an advanced cancer treatment.
Releasing Cancer Cells for Better Analysis
A new device developed at the University of Michigan could provide a non-invasive way to monitor the progress of an advanced cancer treatment.
Apricot Kernels Pose Risk of Cyanide Poisoning
Eating more than three small raw apricot kernels, or less than half of one large kernel, in a serving can exceed safe levels. Toddlers consuming even one small apricot kernel risk being over the safe level.
Cell Transplant Treats Parkinson’s in Mice
A University of Wisconsin—Madison neuroscientist has inserted a genetic switch into nerve cells so a patient can alter their activity by taking designer drugs that would not affect any other cell.
Understanding Female HIV Transmission
Glowing virus maps points of entry through entire female reproductive tract for first time.
Genetic Markers Influence Addiction
Differences in vulnerability to cocaine addiction and relapse linked to both inherited traits and epigenetics, U-M researchers find.
Lab-on-a-Chip for Detecting Glucose
By integrating microfluidic chips with fiber optic biosensors, researchers in China are creating ultrasensitive lab-on-a-chip devices to detect glucose levels.
A lncRNA Regulates Repair of DNA Breaks in Breast Cancer Cells
Findings give "new insight" into biology of tough-to-treat breast cancer.
COPD Linked to Increased Bacterial Invasion
Persistent inflammation in COPD may result from a defect in the immune system that allows airway bacteria to invade deeper into the lung.
Detection of HPV in First-Void Urine
Similar sensitivity of HPV test on first void urine sample compared to cervical smear.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,400+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!