McGill researchers prove ‘junk DNA’ is not just junk

Small differences in DNA have huge effect on our bodies

Karen Fournier, The Concordian (Concordia University)

MONTREAL (CUP) — Minute differences in our individual genetic codes, even in what was previously called “junk DNA,” can change our bodies, according to McGill University researchers.

While junk DNA was once thought to serve no function, this new research explains why people have different physical traits and even why some people develop genetic diseases.

“We used to think that species differed at the protein level. Now we know that there are few protein codings. So, it’s not what kind of protein we produce, but how we express them,” explained Jacek Majewski, assistant professor in McGill’s department of human genetics and the study’s lead researcher.

This information is crucial in understanding how our bodies work and why some people are susceptible to complex diseases such as diabetes, heart disease and asthma, said Majewski.

The study was published in the January issue of Nature Genetics. Tony Kwan, a post-doctoral fellow and the project’s first author, is confident that this achievement will draw more funding to the study, which is currently financed by Genome Canada and Genome Quebec.

The study was based on the finding that small variations in our DNA, called single nucleotide polymorphisms, or SNPs, which are found in junk DNA, have an effect on our bodies’ physical characteristics.

Junk DNA makes up 80 to 90 per cent of the human genome.

Majewski’s team has demonstrated that SNPs (pronounced “snips”) control the processing of messenger RNA, which act as a blueprint for protein assembly, through splicing.

Splicing occurs when useless sequences of messenger RNA are removed from the genetic code.

Once these useless segments are removed, the important sections, called exons, need to be reattached. This can result in different combinations. For example, if exons A, B and C remain, the resulting sequence can be ABC, BAC, CAB and so on.

This explains, in part, why individuals have different traits.

“We knew this mechanism existed and we knew that in some cases it caused disease,” said Majewski. “For example, in cystic fibrosis, splicing is affected. People who have defective splicing are sick. Now we know this is caused by splicing mutations or polymorphisms.”

Each individual has about a million single nucleotide polymorphisms, causing changes in splicing, which in turn leads to drastically altered forms of proteins. And while proteins are the building blocks of our bodies, they also have active functions like participating in immune reactions.

The McGill study proved that a small variation in the genetic code can drastically alter the shape of a protein. When a protein loses its shape, it cannot function with other proteins.

This can be compared to a lock and key mechanism: when the key loses its shape, it can no longer fit into the lock. Scientists think that this may lead to genetic diseases, such as Type 1 diabetes.

In order to complete this study, Majewski’s group had to endure two years of painstaking micro-array analysis.

Microarrays are chips containing microscopic DNA spots, typically from a single gene, which allow researchers to monitor gene expression levels. Benovoy said that a lot of the work was just figuring out how to analyze the massive amounts of data the group had accumulated.

Right now, the study’s findings have no practical applications. It is only a step in finding new treatments or possibly cures for genetic diseases.

Majewski is confident that there will be significant advances in about a year’s time. The next step is to compare healthy and affected individuals in order to try and identify the genes responsible for disease development.