Cholesterol is a crucial fat-like substance produced by the liver that is required for bodily functions. It is the main sterol synthesized and transported in the blood plasma of all animals. Cholesterol is responsible for a number of functions such as:

1. Building and maintenance of the cell membranes
2. Production of sex hormones (androgens and estrogens)
3. Production of bile
4. Metabolism of fat-soluble vitamins, including vitamins A, D, E, and K
5. Insulation of nerve fibers
6. Conversion of sunshine into vitamin D

Cholesterol being a crucial part of our development can have a dark side. The gene DHCR7 (7-dehydrocholesterol reductase) found on chromosome 11 is responsible for the production of cholesterol and mutations in the gene may lead to a metabolic disorder known as SLOS (Smith-Lemli-Opitz Syndrome). This disorder currently occurs once out of every 20,000 births. Individuals with SLOS are unable to produce enough cholesterol to support normal growth and development. This leads to developmental delays, physical malformations, mental retardation and issues with major organs such as the heart. Currently the only treatment for the disorder is cholesterol supplementation to improve growth and developmental progress.

SLOS is inherited in an autosomal recessive pattern, basically both copies of the gene within a cell are mutated. This identifies that the parents of a person with SLOS each carry a mutated copy of the gene, however they do not have any symptoms or signs of SLOS. It may be that genetic counseling may be one form of a preventative method for the disorder. This brings up a great question, should genetic counseling be mandatory for potential parents to decrease transmission of severe genetic disorders?

While most students don’t fully grasp this idea, there are a few examples we can use that can help to explain this.  I have always used examples of giraffes and the development of long necks, or antibiotic resistance in bacteria, but these seem to be a bit out of the realm of many 5^th grade students.  So what better example than ourselves!

During another lesson, I introduced the development of lactase persistence, or having the ability to drink and eat dairy products past infancy.  Digesting the sugar in milk (lactose) is dependent on whether or not the cells of your small intestine are producing the enzyme lactase.  Lactase is responsible for breaking lactose into smaller components that then get absorbed into the bloodstream.  For mammals that get milk from mother early in life, this enzyme is essential.  Would a mutation in the DNA that would allow a cell to continue to make lactase past infancy be beneficial?  It all depends on which population of humans you ask.

If it is a population of humans that began drinking the milk of other animals after the development of agriculture, like those of Northern European descent, it would be selected for.  These populations now show the highest frequency of lactase persistence among all human populations.  If dairy was not a part of your diet after infancy, this mutation wouldn’t be considered beneficial and would not have been selected for, such as in African, Asian and South American populations.

So, when teaching evolution and the changes that we see in species over time, it is nice to be able to give an example that we can see in humans.  Using an example that is a recent development in humans over the last 10,000 years, may help students to understand this concept better, and apply it across any species.

Pharmacogenomics is the ability to study the differences in the DNA of a person to see how they are going to respond to a certain drug.  The DNA contains instructions on how to make proteins.  These proteins then go on to carry out life’s basic functions.  A disorder that may result because of changes in the production of these proteins resulting from mutations in the DNA has been a major area of research for some time.  But now we have to look into how some of these proteins are interacting with the medications that we are taking to treat the disorder.  It is a major shift in the way many people think about DNA and how it affects our health.

Pharmacogenomics is a relatively new area of science that is now looking into these differences in the DNA that cause a person to respond to a drug in a certain way, if at all.  There are a whole group of proteins that are in charge of metabolizing, or breaking down, the medications we take into their active forms.  The instructions in the DNA that make these proteins are different from person to person, so it is these variations that will either make a person make more of the proteins, less, or none at all.  These different levels then cause a person to respond to a drug in a certain way.

For example, if a patient is taking the blood thinner Warfarin to treat blood clots, and they are making too much of the protein that metabolizes this drug, they will break it down too fast and this could possibly thin the blood too much.  If they are a patient that either makes less or none of this protein, the clots will still form, which could still cause serious problems for that patient.  So if we could gather all of the variations in the DNA that lead to certain reactions to drugs, we could use this information to better treat future patients.

A DNA test could be done before the medication is prescribed.  If a patient is showing a similar variation in the DNA to a previous patient that was not able to metabolize a drug, the doctor may want to think twice about prescribing that drug to their patient.  Since we now know that one size does NOT fit all, studying the variations in the DNA to see how their patients will respond to certain drugs will help in prescribing the correct drug and at the right dose.

Featured image from: http://www.genomicslawreport.com/index.php/tag/personalized-medicine/

To find these driver mutations, scientists look for the ones that occur frequently. Until recently, this was very difficult to do. However, new sequencing technologies now let scientists look for mutations in genes at an incredible rate. The cost of sequencing is dropping dramatically; to the point where in the near future sequencing the DNA from a cancer may be sequenced as a diagnostic. Soon, it may be the cost of computing that limits our sequencing efforts.

Improvements in technology allow scientists to look at the genomes of many tumors, and there is an international effort to look at 25000 cancer genomes. This will provide the data that will let them find the mutations that lead to cancer, even if they occur in a small proportion of tumors of a particular kind. Already, hundreds of tumors have been studied in detail, which is giving scientists a good feel for the patterns of mutations that happen in cancer cells. So far, over 400 genes directly linked to cancer have been identified in this and other studies. Figuring out how these many genes contribute to cancer is likely to lead to huge advances in diagnosis and treatment, although the task remains gargantuan.

In a turn-around of sorts, it may be comforting to know that cancers can become addicted, too. Cancer cells have many different genetic changes, as well as changes in the expression of genes that are not due to mutations called epigenetic changes. Although cancer cells do have many differences from normal cells, they are still very similar to normal cells, making it very difficult to find treatments for cancers that don’t have serious side-effects.

Scientists, however, are beginning to identify genes that appear to be “Achilles heels” for cancers. It turns out that in many cases, reversing a defect in just one gene can have a profound effect on the growth of a cancer. Genes that promote cancer when mutated are called oncogenes, so this dependence on a particular genetic change in a cancer is called “oncogene addiction.” Often, treating these changes can be accomplished with little effect on normal cells, because the biology of cancer cells and normal cells has different wiring. So, a cancer cell may need to express a particular protein to keep dividing, while a normal cell might have other ways to keep going.

For instance, HER-2 is a receptor that is expressed on the surface of many breast cancers. HER-2 expressing cancers are often dependant on HER-2 to keep growing. This dependence is exploited in breast cancer treatments by an antibody drug, called Herceptin, which binds and inhibits HER-2.

Just as you can bring a cigarette smoker to their knees by taking away nicotine, so some cancers are tamed by taking away their favorite oncogene. Unfortunately, just like cigarette smokers who turn to other ways to cope, like caffeine or (more healthily) exercise, cancer cells can also escape their addictions, but that is another story…