About Careers Internship MedBlogs Contact us
Medindia LOGIN REGISTER
Advertisement

DiGeorge Syndrome Severity may be Explained by Gene Switch

by Kathy Jones on August 26, 2012 at 9:39 PM
Font : A-A+

 DiGeorge Syndrome Severity may be Explained by Gene Switch

Variations in the severity of birth defects in children with DiGeorge syndrome may be explained by the existence a 'switch' that modifies a gene known to be essential for normal heart development.

Researchers from the Walter and Eliza Hall Institute made the discovery while investigating foetal development in an animal model of DiGeorge syndrome. DiGeorge syndrome affects approximately one in 4000 babies.

Advertisement

Dr Anne Voss and Dr Tim Thomas led the study, with colleagues from the institute's Development and Cancer division, published today in the journal Developmental Cell.

Dr Voss said babies with DiGeorge syndrome have a characteristic DNA mutation on chromosome 22 (22q11 - chromosome 22, long arm, band 11), but exhibit a range of mild to severe birth defects, including heart and aorta defects. "The variation in symptoms is so prominent that even identical twins, with the exact same DNA sequence, can have remarkably different conditions," she said. "We hypothesised that environmental factors were probably responsible for the variation, via changes to the way in which genetic material is packaged in the chromatin," Dr Voss said.
Advertisement

Chromatin is the genetic material that comprises DNA and associated proteins packaged together in the cell nucleus. Chemical marks that sit on the chromatin modify it to instruct when and where to switch genes on or off, making a profound difference to normal development and cellular processes.

The research team found a protein called MOZ, the 'switch' which is involved in chromatin modification, was a key to explaining the range of defects seen in an animal model of DiGeorge syndrome. "MOZ is what we call an chromatin modifier, which means it is responsible for making marks on the chromatin that tell genes to switch on or off," Dr Voss said.

"In this study, we showed that MOZ regulates the major gene, called Tbx1, in the 22q11 deletion. Tbx1 is responsible for heart and aortic arch development. In mouse models that have no Moz gene, Tbx1 does not work properly, and the embryos have similar heart and aorta defects to those seen in children with DiGeorge syndrome. We showed that MOZ is crucial for normal activity of Tbx1, and the level of MOZ activity may contribute to determining how severe the defects are in children with DiGeorge syndrome," Dr Voss said.

Dr Voss said the study also showed that the severity of birth defects in DiGeorge syndrome could be compounded by the mother's diet, particularly if the MOZ switch is not working properly. The research team showed that reduced MOZ activity could conspire with excess retinoic acid (a type of vitamin A) to markedly increase the frequency and severity of DiGeorge syndrome.

"In our mouse model, we saw that retinoic acid exacerbated the defects seen in mice with mutations in the Moz gene. In fact, in mice that had one normal copy of MOZ and one mutated copy, the offspring look completely normal, but if the mother's diet was high in vitamin A, the offspring developed a DiGeorge-like syndrome. This suggests that MOZ, when coupled with a diet high in vitamin A (retinoic acid), may play a role in the development of DiGeorge syndrome in some cases.

"This interaction between the chromatin modifier MOZ, the Tbx1 gene, and retinoic acid in the diet gives a rare insight of how the environment and genetic mutations can interact at the chromatin level to cause birth defects."



Source: Eurekalert
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
What's New on Medindia
Are Menopause Symptoms Troubling You?: Try these Options
Vaccination  And Counter  Measures Against  Monkeypox
Indian Railways Special Concession on Health Grounds
View all
Recommended Reading
News Archive
Date
Category
Advertisement
News Category

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
DNA Finger Printing Weaver Syndrome DiGeorge Syndrome 

Most Popular on Medindia

Sinopril (2mg) (Lacidipine) Diaphragmatic Hernia Find a Doctor Iron Intake Calculator Drug - Food Interactions Indian Medical Journals Blood - Sugar Chart Post-Nasal Drip Blood Pressure Calculator Noscaphene (Noscapine)

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2022

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use