3-D Changes in DNA may Lead to a Genetic Form of Lou Gehrigs Disease
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New findings reveal how a mutation, a change in the genetic code that causes neurodegeneration, alters the shape of DNA, making cells more vulnerable to stress and more likely to die.
The particular mutation, in the C9orf72 gene, is the most common cause for amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease), and frontotemporal degeneration (FTD), the second most common type of dementia in people under 65.
This research by Jiou Wang, PhD, and his colleagues at Johns Hopkins University (JHU) was published in Nature and was partially funded by the National Institutes of Health’s National Institute of Neurological Disorders and Stroke (NINDS).
Using sophisticated molecular techniques, Dr Wang and his team showed that the mutation causes changes in the three-dimensional shape of DNA. DNA is normally shaped like a twisted ladder. However, the repeating sequences can fold into G-quadruplexes, stacks of square-shaped molecules known as G-quartets. "This structure has been described as a square building with each floor representing one G-quartet, normally two to four stories high,” said Dr Wang, senior author of the paper.
Their results also showed that C9orf72 mutated DNA has profound effects on how the genetic message is processed in the cell. RNA, short for ribonucleic acid, acts as an important intermediary — a middleman — in the process that converts genetic information from DNA into functional proteins. This happens in two stages: conversion of the DNA code into RNA is called transcription. RNA then forms proteins during a process known as translation.
To read NIH's full story, click here
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