Series: Sickle Cell, Introduction

                 It’s just one nucleotide!  It’s just one little mistake in a hugely long DNA molecule that causes this disease.  That one little mistake causes soft, happy, healthy red blood cells to turn into arched, half-moon, sticky red blood cells that die quickly, but not before inflaming the patient’s blood vessels.  This leads to pain, anemia and death (with current advances, patients live into their 50s).    Such is the power of one little nucleotide.  Think about that.  

                If you have read my Henrietta Lacks & HPV series, you’ll note that my second post covered HPV-infected patient symptoms at a clinical level, my third post discussed cellular changes that could be seen on an infected cervix and my fourth post explained what was going on inside those infected cells.  We slowly worked our way down from patient level to cellular level to molecular level to explain HPV infection and how it leads to cancer.

                I came across a news article today discussing Ryan Clark and his sickle cell trait (see my Mini-Amedeo post called Sickle Cell Trait).  I was originally going to do a brief synopsis on the disease here and cross the subject over on to Dr. Amedeo with recent advances, but I have a new idea.  Instead, I’m going to work from patient symptoms, down to blood characteristics, and finally discuss what has gone wrong with the patient’s hemoglobin molecules to lead to such a disease.  

I’m a big fan of dissecting diseases in this fashion as a way of explaining them.

            In this, my introductory post, I want to simply establish the idea of inherited disease.

            Genes are strings of DNA bases that encode a protein sequence (see that pesky Central Dogma post).  Nearly every healthy human cell (notable exceptions: male sperm and female eggs) carries two copies of each gene and both are translated.  This kind of redundancy is useful.  What if one copy gets damaged?  One gene is churning out a dysfunctional protein but the other is putting out a perfectly normal version.  Granted, the healthy version will be in lower amounts, but it will still be there and sometimes that is good enough for keeping cells running appropriately.  

                What happens when both copies are damaged?  Well, your cells are now missing that protein.  Interestingly, proteins have redundancy in their functions (life has a lot of built in fail-safe mechanisms).  Sometimes if one protein is missing then another protein can step up and fulfill the function.  However, for some proteins, its loss of function leads to catastrophic results.  This is the case with sickle cell disease. 

                So what’s going on with male sperm and female eggs?

                These cells only have one copy of every gene.  When sperm meets egg, we have the meeting of each gene copy so the growing little baby will now have two copies of everything again.  This means that one gene copy comes from the mother and one comes from the father.  

                So… Mom has two copies of a gene.  One copy goes into one egg and one copy goes into another.  Dad has two copies of a gene.  One copy goes into one sperm and one copy goes into another.  Based on this knowledge, we can start to make some predictions about their children.

Case #1: Mom has two copies of the healthy gene.  Dad has two copies of the healthy gene.  This means that their child will get two healthy genes.

Case #2: Mom has two copies of the damaged gene.  Dad has two copies of the damaged gene.  This means that their child will also have two copies of the damaged gene.

                But, what if the case is more complicated?  What if each parent has a good gene and a bad gene?  What if only one does and the other has two bad genes?  What if the other has two good genes?  What do these situations mean for their child?

                Scientists use a little thing called a Punnett Square to figure it out.  As shown in Figure 50.1, the choices for one parent’s genes are written across the top and the choices for the other parent are written down the side.  Inside each box is written the choice from the top of its column or the end of its row.  The inside of the squares represent all the possibilities for the children.  

Figure 50.1 shows you an example for what happens when each parent has a good gene and a bad gene.  From the results, scientists can say “Your child will have a 25% chance (1 out of 4) of having two bad genes, a 50% chance of having one healthy and one bad (2 out of 4), or a 25% change of having two healthy genes.”  

 

Now, let’s go back to Sickle Cell Disease.  It is caused by two bad genes for the protein hemoglobin.  Just as explained above, people can exist with two healthy hemoglobin genes, two bad hemoglobin genes or one of each.  If you have two bad hemoglobin genes, you have Sickle Cell Disease.  If you have one healthy and one bad, you have Sickle Cell Trait.  If you have two healthy hemoglobin genes, you're normal!  Congrats.

Our next post will compare and contrast patient symptoms for those with Sickle Cell Disease and Sickle Cell Trait.  

Anemia: when the body does not have enough healthy red blood cells.

REFERENCES

Alberts et al. “Molecular Biology of the Cell, 4^th Edition.”  Garland Science, New York, New York. (2002).

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