Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A nucleotide change could initiate fragile X syndrome

01.09.2014

Researchers reveal how the alteration of a single nucleotide—the basic building block of DNA—could initiate fragile X syndrome, the most common inherited form of intellectual disability. The study appears in The Journal of Cell Biology.

Fragile X syndrome is caused by a defect in a gene on the X chromosome called fragile X mental retardation 1 (FMR1). Around 1 in 230 women and 1 in 360 men carry a so-called premutation, in which a series of DNA repeats at one end of the FMR1 gene is slightly longer than normal.


Researchers used genetic mapping to determine that stem cells derived from mothers carrying a fragile X premutation (above) show a normal pattern of DNA replication when a nearby DNA sequence is similar to normal stem cells.

Credit: Gerhardt et al., 2014

These repeats are prone to even further expansion when FMR1 is passed from mother to child, causing the gene to switch off and stop producing a protein that is important for some cognitive functions.

A group of researchers from Albert Einstein College of Medicine of Yeshiva University in New York previously found that a certain site that initiates DNA replication, located near to the FMR1 gene, is inactivated in fragile X embryonic stem cells.

... more about:
»Biology »DNA »FMR1 »Fragile »Health »JCB »Rockefeller »SNP »cytosine »replication »thymine

This inactivation changes the way that the FMR1 gene is copied during cell division, which could pose problems that lead to expansion of the DNA repeats within the gene.

Intriguingly, a specific alteration in the DNA sequence near the FMR1 gene—a "single-nucleotide polymorphism" or SNP— has been linked to an increased risk of repeat expansion in some premutation carriers. These researchers discovered that this SNP overlaps with the inactive replication origin in fragile X embryonic stem cells.

Nucleotides in DNA include one of four bases (cytosine, thymine, adenine, or guanine). The researchers found that normal embryonic stem cells had a thymine base at the SNP site and an active replication origin. Fragile X cells, in contrast, had a cytosine base and an inactive origin.

The researchers also derived embryonic stem cells from mothers carrying the fragile X premutation. These cells had a thymine base and a normal replication pattern and, accordingly, showed no tendency to expand their repeat numbers over time.

The findings show that the substitution of cytosine for thymine might inactivate the DNA replication origin when the FMR1 gene is passed from mother to child, increasing the risk of DNA repeat expansions that can lead to fragile X syndrome.

###

Gerhardt, J., et al. 2014. J. Cell Biol. doi:10.1083/jcb.201404157

About The Journal of Cell Biology

The Journal of Cell Biology (JCB) is published by The Rockefeller University Press. All editorial decisions on manuscripts submitted are made by active scientists in conjunction with our in-house scientific editors. JCB content is posted to PubMed Central, where it is available to the public for free six months after publication. Authors retain copyright of their published works, and third parties may reuse the content for non-commercial purposes under a creative commons license. For more information, please visit http://www.jcb.org.

Research reported in this press release was supported by the National Institute of General Medical Sciences and National Institute of Child Health and Human Development of the National Institutes of Health, Empire State Stem Cell Fund, Starr Tri-Institutional Stem Cell Initiative, and Neurogenomics.

Rita Sullivan King | Eurek Alert!

Further reports about: Biology DNA FMR1 Fragile Health JCB Rockefeller SNP cytosine replication thymine

More articles from Life Sciences:

nachricht Why do animals fight members of other species?
24.04.2015 | University of California - Los Angeles

nachricht Is a small artificially composed virus fragment the key to a Chikungunya vaccine?
24.04.2015 | Paul-Ehrlich-Institut - Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fast and Accurate 3-D Imaging Technique to Track Optically-Trapped Particles

KAIST researchers published an article on the development of a novel technique to precisely track the 3-D positions of optically-trapped particles having complicated geometry in high speed in the April 2015 issue of Optica.

Daejeon, Republic of Korea, April 23, 2015--Optical tweezers have been used as an invaluable tool for exerting micro-scale force on microscopic particles and...

Im Focus: NOAA, Tulane identify second possible specimen of 'pocket shark' ever found

Pocket sharks are among the world's rarest finds

A very small and rare species of shark is swimming its way through scientific literature. But don't worry, the chances of this inches-long vertebrate biting...

Im Focus: Drexel materials scientists putting a new spin on computing memory

Ever since computers have been small enough to be fixtures on desks and laps, their central processing has functioned something like an atomic Etch A Sketch, with electromagnetic fields pushing data bits into place to encode data.

Unfortunately, the same drawbacks and perils of the mechanical sketch board have been just as pervasive in computing: making a change often requires starting...

Im Focus: Exploding stars help to understand thunderclouds on Earth

How is lightning initiated in thunderclouds? This is difficult to answer - how do you measure electric fields inside large, dangerously charged clouds? It was discovered, more or less by coincidence, that cosmic rays provide suitable probes to measure electric fields within thunderclouds. This surprising finding is published in Physical Review Letters on April 24th. The measurements were performed with the LOFAR radio telescope located in the Netherlands.

How is lightning initiated in thunderclouds? This is difficult to answer - how do you measure electric fields inside large, dangerously charged clouds? It was...

Im Focus: On the trail of a trace gas

Max Planck researcher Buhalqem Mamtimin determines how much nitrogen oxide is released into the atmosphere from agriculturally used oases.

In order to make statements about current and future air pollution, scientists use models which simulate the Earth’s atmosphere. A lot of information such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

HHL Energy Conference on May 11/12, 2015: Students Discuss about Decentralized Energy

23.04.2015 | Event News

“Developing our cities, preserving our planet”: Nobel Laureates gather for the first time in Asia

23.04.2015 | Event News

HHL's Entrepreneurship Conference on FinTech

13.04.2015 | Event News

 
Latest News

Electrons Move Like Light in Three-Dimensional Solid

24.04.2015 | Materials Sciences

Connecting Three Atomic Layers Puts Semiconducting Science on Its Edge

24.04.2015 | Materials Sciences

Understanding the Body’s Response to Worms and Allergies

24.04.2015 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>