Heart Abnormalities Traced to Junk DNA Segments

Highlights

• Researchers have found that not all non-coding regions of the DNA are devoid of functions.
• Certain regions of the junk DNA called enhancers play an active role in heart health
• Scientists are creating a map of heart enhancers which will provide a better understanding of diseases.
• The absence of heart enhancers found to lead to abnormalities.

Researchers from Lawrence Berkeley National Laboratory’s Department of Energy have found that certain DNA segments that were considered ‘junk', also called enhancers, were now found to be associated with heart abnormalities. These DNA segments did not code for any specific protein and hence were termed ‘junk’. The researchers found 80,000 DNA segments that were considered junk and they chose 2 of these segments for their study. Senior staff and co-author of the study, Axel Visel, said "The cardiac changes that we observed in knockout mice lacking these enhancers highlight the role of non-coding sequences in processes that are important in human disease. Identifying and interpreting sequence changes affecting non-coding sequences is increasingly a challenge in human genetics. The genome-wide catalog of heart enhancers provided through this study will facilitate the interpretation of human genetic data sets."

Junk DNA

When the entire human genome was sequenced, it was found that only 5% of the genome coded for a specific protein. The rest of the DNA were considered junk.

• A considerable percentage of the genome were considered junk
• These segments of the DNA were initially not believed to have any influence.
• The ENCODE (Encyclopedia of DNA elements) was a comprehensive study that looked at functional elements in DNA sequences.
• The scientists involved with ENCODE stated that nearly 805 of these segments had biochemical functions.
• Scientists believe that junk DNA were formed during evolution when certain genes undergo random mutations that result in the loss of ability to code for proteins. Since there are 2 copies of genes in every organism, mutations in one gene copy will not have too deleterious effect.
• Certain junk DNA have been found to influence certain other genes by switching them on.
• These non coding region of the DNA have been found to play a pivotal role during early stages of development by regulating gene expression.
• Some sections of the junk DNA sequences have also been found to act as ‘enhancers’, they have a direct influence over the rate of expression of nearby gene sequences.
• Some junk DNA sequences act as suppressors that suppress the transcription of certain genes that are close.

80,000 DNA segments that are considered to be heart enhancers have been found in the human genome.

Diane Dickel, who is the lead author of the study said "In genetic studies, the way you establish whether a gene is important is you delete it from the genome and see what happens. In many cases, there are genes that, if disabled, make it difficult for the organism to survive. For enhancers, it's less known what the consequences are if they are damaged or missing. To use a car analogy, if we took the battery out of a car, it wouldn't start. That's a critical component. A missing or damaged enhancer could be essential like a battery, or more similar to a missing passenger seat in the car. It's not as nice, but it's still possible to drive the car."

Creating a Map

Dr. Dickel and colleagues created a map of heart enhancers in the genome using chromatin immunoprecipitation sequencing. This, the scientists believe, will help people understand the basis of diseases better.

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In their study, the researchers disabled these known heart enhancers and compared them with mice with normal heart enhancer function. The scientists carried out an electrocardiogram of the heart of mice from both the groups to understand the effect.

The scientists found that mice with disabled heart enhancers pumped blood less effectively, an indication of cardiomyopathy.

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"Prior to this work, no study had looked at what happens to heart function as a result of knocking out the heart enhancers in the genome. What was surprising to me was that outwardly, the knockout mice seemed fine. If you just looked at them, you wouldn't necessarily see anything wrong," said Dr. Dickel, stressing the significance of the study.

References:

1. The Case for Junk DNA - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4014423/)
2. Junk DNA - (http://www.psrast.org/junkdna.htm)

Source-Medindia