I’m Blue, Oh Ohh, Oh Ohh…

Who doesn’t love learning about a fun genetic disease? And what is more fun than a disease that can turn you blue?!

Hemoglobin is a protein found inside your red blood cells that allows your cells to bind and carry oxygen. Kind of a super important protein. In mammals, 97% of a red blood cell is hemoglobin. A hemoglobin molecule is made up for 8 subunits: 4 protein subunits and 4 iron containing subunits (hemes). The heme groups are what bind, carry and release oxygen molecules. Of the 4 protein subunits, there are 2 types: alpha-globin and beta-globin. A gene called “hemoglobin, beta” (HBB) is what tells the body how to make the beta-globin subunit.

Methemoglobinemia (beta-globin type) is a rare genetic disorder of the blood. Individuals with methemoglobinemia have a few mutations in certain parts of the HBB gene. These mutations cause the body to produce an atypical version of the beta-globin subunit. When this odd version joins the other subunits to form a hemoglobin molecule, it doesn’t join together properly and ends up forming a slightly different protein, hemoglobin-M.

Hemoglobin-M does not interact with the heme groups properly and ends up inhibiting their ability to bind oxygen as well as normal. Poor binding means less oxygen being delivered throughout the body.

We all know that oxygenated blood is red (visualize your arteries, blood dripping from a cut, etc.) and deoxygenated blood is bluish in color (think of your veins). Less oxygen in the bloodstream will make the blood blue as it moves through the body, causing the skin and other membranes of a person with methemoglobinemia to look blue.

A person inherits methemoglobinemia from their parents. It is an autosomal dominant trait. Autosomal means it is not sex-linked (not on an X or Y chromosome); the mutation can come from the mom or dad and will affect both sons and daughters. Dominant means that it only takes one copy of the mutated gene to have the condition. If both parents are blue, there is a very slim chance any children will be normal colored (the best being a ¼ chance if the parents are both heterozygous carriers).

There is not really a treatment to fix this condition, but as long as the person doesn’t mind being blue they will be fine. Most people with methemoglobinemia live very normal lives. The most famous case of methemoglobinemia was the Blue Fugates of Kentucky. After emigrating from France in 1820, Martin Fugate married Elizabeth Smith of Kentucky. They had 7 children and 4 of them popped out blue. Being in the backwoods of Kentucky, the kids obviously married other locals and eventually started inbreeding. The whole area started turning blue. Three blue Fugates were still alive in the 1980s.

“Still Hungry for a Cure!”

Good morning friends! I hope everyone is having a lovely day! Today’s post is going to be about another interesting genetic disorder: Prader-Willi Syndrome (PWS).

Every human has lots and lots of DNA. All of you DNA is packaged up ever-so-carefully by your cells and stored in coiled bars known as chromosomes. Humans have 23 chromosomal pairs: one set from your mom and one set from your dad. Problems with your chromosomes can lead to some major problems in life. And this is the case with Prader-Willi Syndrome. PWS is caused by a problem on a person’s 15th chromosome. Several of the genes on the chromosome from the mom are disrupted and turned off (science jargon: silenced due to imprinting) and/or some of the genes on the chromosome from the dad are missing (deleted). The genes messed up are ones associated with regulating appetite. This is not a disorder created by one little DNA slip-up – a bunch of things are missing. The majority of time these chromosomal issues happen randomly at the time of conception. Very rarely will a parent pass this mutation along to another child. PWS is considered a rare disorder, but a very common rare disorder. Anywhere from one in 12,000 to 15,000 children are born with this disorder.

Ok, so a screwed up 15th chromosome… but what is PWS?

People living with PWS are never full – really, they are always hungry. A flaw in the part of the brain (hypothalamus) that controls hunger makes these people constantly looking to eat. They can become consumed with thoughts of food and eating. PWS also creates a metabolism that requires a lot less calories per day than a typical person. Needing fewer calories coupled with always being hungry can be a very dangerous and potentially fatal situation - supervision is a must. This is especially true for a child. With no supervision, a child with PWS could eat themselves to death.

At birth the baby will have a low birth weight, weak muscles and seem to have a hard time thriving/gaining weight. Typically between the ages of 2-5 is when the super appetite kicks in. PWS is also characterized by social and motor skill issues, lower IQs (around 70), small stature, small hands and feet, obesity, frequent skin picking, OCD tendencies and poor/incomplete sexual development. PWS people are also usually extremely flexible. There is no cure for PWS, but with treatment and a good support group, people can live long happy lives. Further research into PWS could lead to understanding (and possibly curing) the genetics of all obesity issues.

So there is yet another example of how powerful our genes are. Next time I really need to give an example of a positive mutation – a mutation does not always create a bad outcome.

One Singular Deletion…

Everyone that knows me knows I love love love genetics. I have not talked about genetics yet because I didn’t want to lose people in the jargon (or out of boredom). To change that, I decided to spark your interest in genetics with a super rare genetic condition I did a project on in college: Progeria.

Progeria (aka: Hutchinson–Gilford syndrome) is a genetic disease that causes early aging. It occurs in about 1 in 4 million births. Children born with this condition look average when they pop out, but within a few months they show a lack of growth. Kids with progeria will develop normally mentally, but physically they will be much smaller, with aged looking skin, extreme hair loss and undersized jaw and face bones compared to their larger skulls. With progeria, a 7 year old will face ailments that most people will not begin experiencing until their 50s, including hip problems, arthritis, and heart issues. Unfortunately there is no treatment or cure for progeria and the condition is fatal. Most progeria patients die by the age of 13 due to heart attack or stroke.

I know! I know! Wow, Robert, way to post a sad one. I did it because I want to show you how crazy genetics can be…

You would think a person born with progeria must have a bunch of genes and DNA screwed up or missing. Here is the crazy part – only 1 thing is different. That’s it - one single difference between a normal baby and a baby born with progeria.

Everyone flash back to middle school biology and learning about DNA. DNA is made up of A, T, C and G and the order of those letters determine what the gene does. Well in the middle of your first chromosome there is a gene called the lamin A gene. This gene encodes for the Lamin A protein. 1,824 letters into this gene, a single letter is screwed up and replaced with another (wrong) letter. This is known as a point mutation. You do not inherit point mutations, nor do pass them along – they just happen. They can cause good or bad results and occur all of the time. Your body has lots of ways of trying to fix them, but that’s a whole different post. This mutation in the lamin A gene causes a snowball effect in the body and ends up making the Lamin A protein non-functional. This Lamin A protein is known to help stabilize the nucleus of cells in the body – a SUPER important job. With it not working, the nucleus is unstable and then you get more of a snowball effects until you end up with progeria.

Isn’t that crazy? There are over 3 billion pairs of letters in the human genome and a mistake in only one can have such catastrophic events.

That’s why I think genetics is amazing.