Genetics seems rather intimidating, but in its purest sense it is rather simple. The basis of genetics is fairly simple: DNA => RNA =>  A Protein.

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DNA, or deoxyribonucleic acid, (DNA) is a long molecule that contains our unique genetic code.  Nearly every cell in a person’s body has the same DNA. Most DNA is located in the cell nucleus (where it is called nuclear DNA), but a small amount of DNA can also be found in the mitochondria (where it is called mitochondrial DNA or mtDNA).

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 The information in DNA is stored as a code made up of four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T). Human DNA consists of about 3 billionof these bases, and more than 99 percent of those bases are the same in every person. The order, or sequence, of these bases determines the information available for building and maintaining an organism.

 DNA bases pair up with each other, A with T and C with G, to form units called base pairs. Each base is also attached to a sugar molecule and a phosphate molecule. Together, a base, sugar, and phosphate are called a nucleotide. Nucleotides are arranged in two long strands that form a spiral called a double helix. The structure of the double helix is somewhat like a ladder, with the base pairs forming the ladder’s rungs and the sugar and phosphate molecules forming the vertical sidepieces of the ladder.

Ribonucleic acid (RNA) is very similar to DNA, but differs in a few important structural details: RNA nucleotides contain ribose sugars while DNA contains deoxyribose and RNA uses predominantly uracil instead of thymine present in DNA. RNA is transcribed (synthesized) from DNA by enzymes called RNA polymerases and further processed by other enzymes. RNA serves as the template for translation of genes into proteins, transferring amino acids to the ribosome to form proteins, and also translating the transcript into proteins.

RNAs serve as the working set of blue prints for a gene. Each gene is read, and then the messenger RNAs are sent to the molecular factories (ribosomes) that build proteins. These factories read the blueprints and use the information to make the appropriate protein. When the cell no longer needs to make any more of that protein, the RNA blueprints are destroyed. but because the master copy in the DNA remains intact, the cell can always go back to the DNA and make more RNA copies when it needs more of the encoded protein.

An example would be the sun’s UV light activating the genes in your skin cells to tan you. The gene is read and the RNA takes the message or blueprint to the ribosomes where melanin, the protein that tans your skin, is made.

DNA Mutations

As we discussed, each gene is made up of a series of bases and those bases provide instructions for making a single protein. Any change in the sequence of bases may be considered a mutation. Most of the mutations are “naturally-occurring.” For example, when a cell divides, it makes a copy of its DNA — and sometimes the copy is not quite perfect. That small difference from the original DNA sequence is a mutation.

Mutations can also be caused by exposure to specific chemicals, metals, viruses, and radiation. These have the potential to modify the DNA. This is not necessarily unnatural — even in the most isolated and pristine environments, DNA breaks down. Nevertheless, when the cell repairs the DNA, it might not do a perfect job of the repair. So the cell would end up with DNA slightly different than the original DNA and hence, a mutation.

Some mutations have little or no effect on the protein, while others cause the protein not to function at all. Other mutations may create a new effect that did not exist before. Many diseases are a result of mutations in certain genes. One example is the gene for sickle cell anemia. The mutation causing the blood disorder sickle cell anemia is a single nucleotide substitution (A to T) in the base number 17 out of 438 A’s, T’s, C’s and G’s . By changing the amino acid at that point, the impact is that the red blood cells are no longer round, but sickle in shape and carry less oxygen.

Some of these changes occur in cells of the body such as in skin cells as a result of sun exposure. Fortunately these types of changes are not passed on to our children. However, other types of errors can occur in the DNA of cells that produce the eggs and sperm. These errors are called germ line mutations and can be passed from parent to child. If a child inherits a germ line mutation from their parents, every cell in their body will have this error in their DNA. Germ line mutations are what cause diseases to run in families, and are responsible for hereditary diseases.

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Genetics and Arrhythmias

Sudden cardiac death (SCD) is a widespread health problem with several known inherited causes. Inherited SCD generally occurs in healthy individuals who do not have other conventional cardiac risk factors. Mutations in the genes in charge of creating the electrical activity of the heart have been found to be responsible for most arrhythmias, among them Short QT Syndrome, Long QT Syndrome, Brugada Syndrome, Familial Bundle Branch Block, Sudden Infant Death Syndrome and Sudden Unexpected Death Syndrome.

Molecular Genetics and the Future of Medicine

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As researchers discover the role genes play in disease, there will be more genetic tests available to help doctors make diagnoses and pinpoint the cause of the disease. For example, heart disease can be caused either by a mutation in certain genes, or by environmental factors such as diet or exercise to name a few.

Physicians can easily diagnose a person with heart disease once they present symptoms. However, physicians can not easily identify the cause of the heart disease is in each person. Thus, most patients receive the same treatment regardless of underlying cause of the disease.

In the future, a panel of genetic tests for heart disease might reveal the specific genetic factors that are involved in a given person. People with a specific mutation may be able to receive treatment that is directed to that mutation, thereby treating the cause of the disease, rather than just the symptoms.

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The ultimate goal of the MMRL’s Molecular Genetics Program is to identify the factors that are responsible for these diseases. This knowledge will facilitate the development ofgene-specific therapies and cures for arrhythmias and identify individuals at risk for sudden cardiac deaths.

With the addition of the Molecular Biology and Molecular Genetics programs, MMRL is now integrally involved in both basic and clinical research, and is among the relatively few institutions worldwide with a consistent and concerted focus on bridging basic and clinical science. With an eye toward designing specific treatments and cures for disease, the Laboratory’s research has the potential to affect us all.

Inherited Cardiac Arrhythmia Syndromes