Genetic Phonetics Could Be The Trick To Sounding Out DNA's Meaning

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Genetic Phonetics Could Be The Trick To Sounding Out DNA's Meaning

http://www.sciencedaily.com/releases/2007/08/070817132905.htm

Most modern attempts to decipher how portions of genetic code are

translated into physical characteristics are akin to a first-grader

trying to sound out a word letter by letter — or, in this case, base

pair by base pair.

But University of Florida researchers have developed a computational

method that's more like reading whole words at a time.

In a world where science's ability to transcribe an organism's

genetic code is growing faster every day, the technique could offer

much needed efficiency in translating the seemingly endless string

of characters into information that can cure disease or create new

crops.

The researchers, from UF's Institute of Food and Agricultural

Sciences and the UF Genetics Institute, published their verification

of the method in PLoS One, an online journal produced by the Public

Library of Science.

" We worked very hard to find ways to collect genetic information, "

said Rongling Wu, the project's lead researcher and a UF Research

Foundation professor. " We now must work hard to find ways to use it. "

In many respects, researchers think of an organism's genome as

ticker-tape listings of four letters — representing four amino acid

bases — repeated in varying orders. The goal is to find meaning

within the sequences, to figure out how variations in the pattern

affect the organism's physiology.

Humans, for example, have 3 billion letters in our code. Between any

two of us, 99.9 percent of those letters are the same. But it's that

last 0.1 percent of difference, peppered throughout our DNA in the

form of single-letter changes, that accounts for our unique

identities—from eye color to disease susceptibility.

These differences are called single nucleotide polymorphisms, or

SNPs (pronounced " snips " ).

The simplest way to find out how a SNP affects an organism is to

collect a group of organisms that have different variations of that

letter in their genetic code.

But physical traits are typically affected by multiple SNPs that

interact in sometimes unpredictable ways — much like the way an " e "

at the end of a word can change its pronunciation.

Fortunately, the rules of genetics say that SNPs that affect the

same trait are generally related to each other in some way, such as

being near each other.

Wu's model uses these rules in conjunction with statistical analysis

of real data from genetically mapped organisms. As a result, the

model can find whole groups of SNPs associated with a physical trait.

Just as an understanding of general phonetic principles allows a

reader to sound out a whole word, this extra knowledge of genetics

allows Wu's model to find whole pictures of genome/physical

correlations.

" The real promise of Wu's work is that it could offer the

opportunity for a researcher to not spend a really disheartening

amount of time parsing out individual nucleotides, and move more

directly to doing the type of genetic work that's going to have a

greater significance, " said Rory Todhunter, a researcher working

with canine genetics at Cornell University.

In the paper, the researchers verified their model using genetic and

physical information from mice that was first collected from the

Washington University lab of Cheverud in the mid-1990s. They

then compared their results with several years' worth of genetic

analysis.

This validation was important, said Wei Hou, the first author of the

paper and an assistant professor at UF's department of epidemiology

and health policy research. But the analysis of modern data will be

the real key to the technique's importance. For example, the mouse

genetic information used in this paper featured only a few thousand

SNPs. The July 29 issue of the journal Nature cited more than 8

million SNPs for the mouse genome.

" This shows how we need to move beyond looking at genomes SNP by

SNP, " Cheverud said. " Imagine the work that's ahead of us if we

don't. "