Tag Archives: Matt Huentelman

chromosome

TGen uses X chromosome to uncover disorders in girls

Using a basic genetic difference between men and women, the Translational Genomics Research Institute (TGen) has uncovered a way to track down the source of a neurological disorder in a young girl.

TGen’s discovery relies on a simple genetic fact: Men have one X and one Y chromosome, while women have two X chromosomes. This women-only factor was leveraged by TGen investigators to develop a highly accurate method of tracking down a previously unrecognized disorder of the X-chromosome.

The study of a pre-teen girl, who went years with an undiagnosed neurobehavioral condition, was published today in the scientific journal PLOS ONE.

TGen’s findings were made within its Dorrance Center for Rare Childhood Disorders, where investigators and clinicians apply the latest tools of genomic medicine to provide answers for parents seeking to identify the disease or disorder affecting their child.

The scientists sequenced, or spelled out in order, the complete genetic codes of DNA and RNA of the girl. Because girls inherit an X chromosome from each of their parents (boys inherit a Y chromosome from their father), they also sequenced her mother and father. On average, about half of all X chromosomes active in a female come from the mother and the other half from the father.

“We now have the tools to significantly accelerate the diagnostic process, reducing the need for children to undergo multiple tests that can be emotionally and physically taxing for the entire family,” said Dr. David Craig, TGen’s Deputy Director of Bioinformatics, Co-Director of the Dorrance Center and the paper’s senior author.

Sequencing would reveal the proportion of X chromosomes, and if disproportionate, whether the more abundant of the two were damaged in some way, which often leads to X-linked genetic conditions.

“At the time of enrollment, we suspected the girl had a complex neurobehavioral condition, based on her attention deficit, and delays in development and learning,” said Dr. Vinodh Narayanan, Medical Director of the Dorrance Center. “Her brain MRI scans were normal. We needed to find out more — at the genetic level — about what might be causing her disorder.”

By sequencing the DNA and RNA, TGen investigators were able to precisely identify which cells contained active X chromosomes from the girl’s mother, which contained active X chromosomes from the father, in what proportions, and whether they were associated with any known disorders.

They discovered that the X chromosome from the father contained a segment shown to be associated with neurobehavioral conditions. Interestingly, however, the proportion of X chromosomes active in the girl’s cells skewed toward the normal X inherited from her mother. This skewing may have led to a milder, harder to diagnose condition undetected by conventional methods.

“This study shows the power sequencing holds when scanning for potential disease causing and disease-modifying genetic variations,” said Dr. Matt Huentelman, the other Co-Director of the Dorrance Center and an author of the PLOS ONE paper. “I’m most excited to see the pace at which TGen has pushed the genome sequencing technology to where it can help patients — today.”

TGen Research Associate Szabolcs Szelinger, the paper’s lead author, said: “With just a small bio sample, we are now able to provide a comprehensive evaluation of the effects that genetic variation has on patients, leading to highly personalized treatment options, while at the same time providing researchers with insights into the underlying molecular processes.”

Since opening in October 2013, TGen’s Dorrance Center for Rare Childhood Disorders Dorrance Center has enrolled nearly 300 families. And with the rapid decrease in sequencing costs and improved analytical methods, comprehensive, integrative sequencing approaches will likely be used more in the future. Information on the Dorrance Center is available at www.c4rcd.org.

Funding for the study came from the State of Arizona, the Stardust Foundation, and donations to the TGen Foundation.

prevention trial - brain scan images

TGen scientist launches innovative online research project

A scientific researcher at Phoenix-based Translational Genomics Research Institute (TGen) has launched a first-of-its-kind online memory test to help better understand human cognition and how it might relate to Alzheimer’s disease and other brain disorders.

Dubbed “MindCrowd”, the study seeks to attract 1 million individuals, aged 18 to 80, willing to complete the 10-minute online memory test at mindcrowd.org. Researchers will use the test results to build a base of data for further study on how cognition and memory changes as people age.

Eventually, the researchers want to leverage this newly-gained biological insight into therapeutic application — treatment. The hope is for the online test to go viral with friends, families and colleagues challenging one another to take the test and compare the results.

MindCrowd is the brainchild of TGen Associate Professor Dr. Matt Huentelman who believes understanding how the brain works in healthy individuals will foster the development of new medicines and therapies for those with brain disorders. Dr. Huentelman’s TGen lab studies the genomics of human neurological traits and diseases with a specific focus on learning, memory and Alzheimer’s.

“MindCrowd is the first research project of its kind,” said Huentelman, an expert in genomics as it relates to memory. “By harnessing the power of the Internet, we can study a million – or more – individuals to help bring us closer to a cure for Alzheimer’s disease and other brain disorders. Combining our knowledge of human genetics and neuroscience with an online research study like MindCrowd is a revolutionary approach to understanding our differences in brain performance and how it may influence risk for disease. We expect to add significantly to our understanding of cognition and how genetic factors impact our memory as we age.”

The MindCrowd project has two phases: Phase I involves memory testing of 1 million or more study participants. Following an in-depth analysis of Phase I test results, researchers will then solicit a subset of Phase I participants willing to donate a DNA saliva sample and undergo an additional round of online testing.

Participation is encouraged from a broad range of ages, backgrounds and cognitive abilities. Those taking the test are free to remain anonymous, although it is encouraged that people share basic data to help the project succeed. The test does not predict or diagnose any condition, rather it provides data on one type of memory and how these processes change as people age and have varied life experiences.

MindCrowd is a collaborative effort among leading scientific research institutions and organizations including TGen, the University of Arizona, Banner Alzheimer’s Prevention Initiative and others.

Visit www.mindcrowd.org to take the test.