NON CODING HALF OF HUMAN GENOME UNLOCKED WITH NOVEL SEQUENCING TECHNIQUE
An obscure swatch of
human DNA once thought to be nothing more than biological trash may actually
offer a treasure trove of insight into complex genetic-related diseases such as
cancer and diabetes, thanks to a novel sequencing technique developed by
biologists at Texas A&M University
The game-changing
discovery was part of a study led by Texas A&M biology doctoral candidate
John C. Aldrich and Dr. Keith A. Maggert, an associate professor in the
Department of Biology, to measure variation in heterochromatin. This
mysterious, tightly packed section of the vast, non-coding section of the human
genome, widely dismissed by geneticists as "junk," previously was
thought by scientists to have no discernable function at all.
In the course of his
otherwise routine analysis of DNA in fruit flies, Aldrich was able to monitor
dynamics of the heterochromatic sequence by modifying a technique called
quantitative polymerase chain reaction (QPCR), a process used to amplify
specific DNA sequences from a relatively small amount of starting material. He
then added a fluorescent dye, allowing him to monitor the fruit-fly DNA changes
and to observe any variations.
Aldrich's findings,
published today in the online edition of the journal PLOS ONE,
showed that differences in the heterochromatin exist, confirming that the junk
DNA is not stagnant as researchers originally had believed and that mutations
which could affect other parts of the genome are capable of occurring.
"We know that
there is hidden variation there, like disease proclivities or things that are
evolutionarily important, but we never knew how to study it," Maggert
said. "We couldn't even do the simplest things because we didn't know if
there was a little DNA or a lot of it.
"This work opens
up the other non-coding half of the genome."
Maggert explains that
chromosomes are located in the nuclei of all human cells, and the DNA material
in these chromosomes is made up of coding and non-coding regions. The coding
regions, known as genes, contain the information necessary for a cell to make
proteins, but far less is known about the non-coding regions, beyond the fact
that they are not directly related to making proteins.
"Believe it or
not, people still get into arguments over the definition of a gene,"
Maggert said. "In my opinion, there are about 30,000 protein-coding genes.
The rest of the DNA -- greater than 90 percent -- either controls those genes
and therefore is technically part of them, or is within this mush that we study
and, thanks to John, can now measure. The heterochromatin that we study
definitely has effects, but it's not possible to think of it as discrete genes.
So, we prefer to think of it as 30,000 protein-coding genes plus this one big,
complex one that can orchestrate the other 30,000."
Although other methods
of measuring DNA are technically available, Aldrich notes that, as of yet, none
has proven to be as cost-effective nor time-efficient as his
modified-QPCR-fluorescence technique.
"There's some
sequencing technology that can also be used to do this, but it costs tens of
thousands of dollars," Aldrich said. "This enables us to answer a
very specific question right here in the lab."
The uncharted genome
sequences have been a point of contention in scientific circles for more than a
decade, according to Maggert, a Texas A&M faculty member since 2004. It had
long been believed that the human genome -- the blueprint for humanity,
individually and as a whole -- would be packed with complex genes with the
potential to answer some of the most pressing questions in medical biology.
When human DNA was
finally sequenced with the completion of the Human Genome Project in 2003, he
says that perception changed. Based on those initial reports, researchers
determined that only two percent of the genome (about 21,000 genes) represented
coding DNA. Since then, numerous other studies have emerged debating the
functionality, or lack thereof, of non-coding, so-called "junk DNA."
Now, thanks to
Aldrich's and Maggert's investigation of heterochromatin, the groundwork has
been laid to study the rest of the genome. Once all of it is understood,
scientists may finally find the root causes and possibly treatments for many
genetic ailments.
"There is so much
talk about understanding the connection between genetics and disease and
finding personalized therapies," Maggert said. "However, this topic
is incomplete unless biologists can look at the entire genome. We still can't
-- yet -- but at least now, we're a step closer."
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