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Where’s Waldo’s DNA? New NIST SRM joins search

29.03.2005


A new reference standard from the National Institute of Standards and Technology (NIST) may help genetics labs develop improved methods of searching for a mutant needle in a DNA haystack.



A single DNA molecule carrying part of a person’s genetic code is a chain of basic chemical units called nucleotides. The number of nucleotides can range from about 16,500 in mitochondrial DNA (mtDNA) to several million in nuclear DNA. A key mutation in a DNA strand may involve only a single nucleotide and yet cause serious health effects.

Accurate analysis of mitochondrial DNA (mtDNA), either for forensic identification or for studying genetic-based diseases, often hinges on the ability to detect such mutations that occur only infrequently, even in the same individual. Unlike the cell’s nuclear DNA, a person’s mtDNA is often heteroplasmic--a mix of a dominant DNA sequence with fewer mutated sequences that differ from the dominant version by one or more nucleotides. There are hundreds or thousands of mitochondria in cells, and the exact percentage of the minority mtDNA in the mix can vary dramatically in an individual from tissue to tissue and even from cell to cell. In general, it can be very difficult to identify variants that make up less than 20 percent of the sample unless you already know they are there.


Researchers face a similar problem of detecting low-frequency variants when analyzing pooled samples of nuclear DNA from a population of individuals in the hope of identifying specific mutations responsible for genetic diseases.

To help the research community develop and test more sensitive techniques for detecting low-frequency mutations in heteroplasmic DNA, NIST researchers have developed a new Standard Reference Material, SRM 2394, "Heteroplasmic Mitochondrial DNA Mutation Detection Standard." The new material is a set of mixtures, at 10 different certified concentrations, of two DNA fragments that differ from each other at only one position.

Michael Baum | EurekAlert!
Further information:
http://www.nist.gov

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