Tag Archives: DNA Clock

University of British Columbia study: New DNA ‘clock’ could help measure development in young children

19 Oct

Rachel Nuwer wrote in the Scientific American article, Programming a DNA Clock: Engineers have created a DNA-based chemical “oscillator,” opening the door to molecular computing:

Nature is a master at constructing biological machines and circuits, including the ones that maintain the body’s internal clock, copy genes or help cells move. Now human engineers are learning to design and synthesize novel biochemical devices such as nanoscale factories, biological circuits and even molecular computers.
This work has so far relied mostly on using existing cellular components (enzymes, for example), but some researchers prefer to start from scratch. For these “molecular programmers,” DNA is the coding language of choice, and crafting circuits and machines to rival those found in nature is the ultimate goal. Recently they took a big step closer by creating the first oscillator—a molecular clock—made solely of DNA.
This milestone achievement, reported last December in Science, shows that DNA is not simply a passive carrier of genetic information. Instead it is a molecule that—even on its own—“is capable of complex behavior,” says senior author David Soloveichik, an electrical and computer engineer at the University of Texas at Austin. Building a DNA oscillator is a biological engineering feat in itself and would likely be integral for potential breakthroughs in synthetic biology, such as controlling the timing of events in artificial cells, scheduling the release of drugs and synchronizing molecular computers.
To create the device, Soloveichik, Niranjan Srinivas, then a doctoral candidate at the California Institute of Technology, and their colleagues built a DNA compiler—a series of algorithms that allows a programmer to issue molecule-building instructions without having to get into the nitty-gritty biochemistry. Software translates those instructions into DNA sequences that are synthesized and mixed together. The strands then self-assemble into molecular machines.
Using its compiler, the team programmed a prototype DNA oscillator that generates repeating patterns of “ticks” and “tocks.” In principle, Soloveichik says, the same formula can be used to produce more complex behavior, such as changing the clock’s speed in response to chemical signals. These clocks could eventually lead to chemical computation—after all, some of the first mechanical computers were simply sophisticated clocks…. https://www.scientificamerican.com/article/programming-a-dna-clock/

Scientists have been studying and designing DNA Clocks. See, DNA clock helps to get measure of people’s lifespans https://www.sciencedaily.com/releases/2015/01/150130092913.htm

Ricki Lewis, PhD wrote A New Biological Aging Clock: Ribosomal DNA:

A new biological clock could be put to good use. “Determining biological age is a central step to understanding fundamental aspects of aging as well as developing tools to inform personal and public health choices. We have hopes that the ribosomal clock will provide new insights into the impact of the environment and personal choices on long-term health,” said Dr. Lemos.
• assessing the effects of cancer treatments on biological aging, perhaps through a cheek swab test
• detecting how environmental exposures like pollution or factors such as lack of exercise or malnutrition affect biological aging
• determining the age structure of a natural population, perhaps through feces analyses
• estimating the age of a stray cat or dog. The animal shelter deemed our new cat Milton as 3, based on his teeth. Might his rDNA provide a more accurate assessment? This approach could be extended to checking the age of humans.
• manufacturers of cosmetics and skin care products can combine rDNA with SPF measurements to dole out dollops customized to how long a customer has until wrinkles appear…. https://blogs.plos.org/dnascience/2019/03/28/a-new-biological-aging-clock-ribosomal-dna/

The University of British Columbia studied the use of a DNA clock to measure development in young children.

Science Daily reported in New DNA ‘clock’ could help measure development in young children:

Scientists have developed a molecular “clock” that could reshape how pediatricians measure and monitor childhood growth and potentially allow for an earlier diagnosis of life-altering development disorders.
The research, published this week in PNAS, describes how the addition of chemical tags to DNA over time can potentially be used to screen for developmental differences and health problems in children.
The study was led by researchers at BC Children’s Hospital, the University of British Columbia (UBC) and the University of California, Los Angeles. It is the first study to describe a method specifically designed for children, called the Pediatric-Buccal-Epigenetic (PedBE) clock, which measures chemical changes to determine the biological age of a child’s DNA.
Small chemical changes to DNA, known as epigenetic changes, alter how genes are expressed in certain tissues and cells. Some of these changes happen as a person ages and others may be in response to a person’s environment or life experiences.
In adults, these patterns of epigenetic changes are well established. They can be used to accurately predict a person’s age from a DNA sample or, if a person’s epigenetic age differs from their actual age, it can point differences in health, including age-related diseases and early mortality.
“We have a good idea how these DNA changes occur in adults, but until now we didn’t have a tool that was specific for children,” says Dr. Michael Kobor, senior author of study. “These DNA changes occur at very different rates in kids and so we adapted this technique for younger ages….”
The PedBE clock was developed using DNA methylation profiles from 1,032 healthy children whose ages ranged from a few weeks old to 20 years. The researchers found 94 different sites in the genome that, when tested together, could accurately predict a child’s age to within about four months. The team also found that children who spent longer in the womb showed an accelerated rate of DNA change by three months, demonstrating that this tool could be used to indicate an infant’s developmental stage. The analysis can be done cheaply and efficiently on cells collected from a cheek swab.
“This powerful and easy-to-use tool could be used by clinicians to identify why some children aren’t meeting early milestones and potentially diagnose children with developmental disorders earlier in life,” says Dr. Lisa McEwen, first author on the study. “This would enable doctors and pediatricians to intervene sooner in a child’s life leading to better outcomes for kids.”
In a small pilot study, the researchers also found that children with autism spectrum disorder (ASD) showed a higher PedBE “age” than those considered to be developing typically, suggesting that the clock could be used to screen for ASD…. https://www.sciencedaily.com/releases/2019/10/191015140253.htm

Citation:

New DNA ‘clock’ could help measure development in young children
Date: October 15, 2019
Source: University of British Columbia
Summary:
Scientists have developed a molecular ‘clock’ that could reshape how pediatricians measure and monitor childhood growth and potentially allow for an earlier diagnosis of life-altering development disorders.

Journal Reference:
Lisa M. McEwen, Kieran J. O’Donnell, Megan G. McGill, Rachel D. Edgar, Meaghan J. Jones, Julia L. MacIsaac, David Tse Shen Lin, Katia Ramadori, Alexander Morin, Nicole Gladish, Elika Garg, Eva Unternaehrer, Irina Pokhvisneva, Neerja Karnani, Michelle Z. L. Kee, Torsten Klengel, Nancy E. Adler, Ronald G. Barr, Nicole Letourneau, Gerald F. Giesbrecht, James N. Reynolds, Darina Czamara, Jeffrey M. Armstrong, Marilyn J. Essex, Carolina de Weerth, Roseriet Beijers, Marieke S. Tollenaar, Bekh Bradley, Tanja Jovanovic, Kerry J. Ressler, Meir Steiner, Sonja Entringer, Pathik D. Wadhwa, Claudia Buss, Nicole R. Bush, Elisabeth B. Binder, W. Thomas Boyce, Michael J. Meaney, Steve Horvath, Michael S. Kobor. The PedBE clock accurately estimates DNA methylation age in pediatric buccal cells. Proceedings of the National Academy of Sciences, 2019; 201820843 DOI: 10.1073/pnas.1820843116

Here is the press release from the University of British Columbia:

New DNA “clock” could help measure development in young children
October 15, 2019
Scientists have developed a molecular “clock” that could reshape how pediatricians measure and monitor childhood growth and potentially allow for an earlier diagnosis of life-altering development disorders.
The research, published this week in PNAS, describes how the addition of chemical tags to DNA over time can potentially be used to screen for developmental differences and health problems in children.
The study was led by researchers at the University of British Columbia (UBC), BC Children’s Hospital, and the University of California, Los Angeles. It is the first study to describe a method specifically designed for children, called the Pediatric-Buccal-Epigenetic (PedBE) clock, which measures chemical changes to determine the biological age of a child’s DNA.
Small chemical changes to DNA, known as epigenetic changes, alter how genes are expressed in certain tissues and cells. Some of these changes happen as a person ages and others may be in response to a person’s environment or life experiences.
In adults, these patterns of epigenetic changes are well established. They can be used to accurately predict a person’s age from a DNA sample or, if a person’s epigenetic age differs from their actual age, it can point differences in health, including age-related diseases and early mortality.
“We have a good idea how these DNA changes occur in adults, but until now we didn’t have a tool that was specific for children,” says Dr. Michael Kobor, a UBC professor in the department of medical genetics, investigator at BC Children’s Hospital and senior study author. “These DNA changes occur at very different rates in kids and so we adapted this technique for younger ages.”
Dr. Kobor is also an investigator at the Centre for Molecular Medicine and Therapeutics, the Canada Research Chair in Social Epigenetics and the Sunny Hill BC Leadership Chair in Child Development.
The PedBE clock was developed using DNA methylation profiles from 1,032 healthy children whose ages ranged from a few weeks old to 20 years. The researchers found 94 different sites in the genome that, when tested together, could accurately predict a child’s age to within about four months. The team also found that children who spent longer in the womb showed an accelerated rate of DNA change by three months, demonstrating that this tool could be used to indicate an infant’s developmental stage. The analysis can be done cheaply and efficiently on cells collected from a cheek swab.
“This powerful and easy-to-use tool could be used by clinicians to identify why some children aren’t meeting early milestones and potentially diagnose children with developmental disorders earlier in life,” says Dr. Lisa McEwen, lead study author who completed this research as a UBC PhD candidate in Dr. Kobor’s lab. “This would enable doctors and pediatricians to intervene sooner in a child’s life leading to better outcomes for kids.”
In a small pilot study, the researchers also found that children with autism spectrum disorder (ASD) showed a higher PedBE “age” than those considered to be developing typically, suggesting that the clock could be used to screen for ASD.
“The fact that our pediatric clock was able to distinguish between typically developing children and those with autism in this small experiment demonstrates the powerful potential of this tool,” says Dr. Kobor. “Although more research is needed to confirm this, these results show that the PedBE clock could be an important factor in evaluating how children develop.”
The researchers made the tool freely available along with the publication of this study so other research teams are able to use and experiment with the tool right away.
A version of this story originally appeared on the BC Children’s Hospital website. https://www.med.ubc.ca/news/new-dna-clock-could-help-measure-development-in-young-children/
Richard Harris wrote about potential uses of DNA diagnosis in A Boy’s Mysterious Illness Leads His Family On A Diagnostic Odyssey https://www.npr.org/sections/health-shots/2019/10/16/769462793/a-boys-mysterious-illness-leads-his-family-on-a-diagnostic-odyssey

The most beautiful thing we can experience is the mysterious. It is the source of all true art and science.
Albert Einstein

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