Genetics of CF

Fair Warning: This is going to be a pretty science-y post.

I have explained what Cystic Fibrosis is but I haven't explained what causes it. Get ready for a crash course in genetics. I actually took a genetics course in undergrad. Hard stuff but so very interesting. Hopefully, my science-y side can paint a clear picture here.

But first, he's a little treat to get you through this technical post:

Feel better? I do! Let's commence...

Every person has genetic information which tells the body how to form and how to function. All of that information is held on structures called chromosomes. We have 23 pairs of chromosomes; one pair comes from our mother and the other pair comes from our father. Like this:

Chromosomes are numbered in pairs from 1 to 22  and the final pair are our sex chromosomes, X and Y, that determine if we are male or female.

Chromosomes are microscopic in size, but hold a huge amount of information. The information is grouped into specific sets of instructions, called genes. Genes are what determine our physical looks, like hair color, eye color, height, ect. The genes supply the body with instructions for making certain proteins, which are the building blocks of the body. These proteins affect the body’s health, growth and development. 

All of this genetic information is written in code and stored as a chemical called DNA. The DNA code is made up of letters that spell out the instructions in genes. CFTR is a gene on chromosome 7. 

We all have two CFTR genes. The CFTR gene provides instructions for making a protein called the cystic fibrosis transmembrane conductance regulator. Say what?! Long name, I know. This protein acts as a bridge across the outer surface of the cells that produce mucus, sweat, saliva, tears, and digestive enzymes.

The bridge transports negatively charged particles called chloride ions into and out of cells. The transport of chloride ions helps control the movement of water in tissues, which is necessary for the production of thin, freely flowing mucus. The CFTR protein also regulates the function of other channels, such as those that transport positively charged particles called sodium ions across cell membranes. These channels are necessary for the normal function of organs such as the lungs and pancreas.

There are small differences in all our CFTR genes. Theses differences may cause the CFTR protein to be different, but it is still working correctly, transporting chloride and sodium ions across the cell membranes. However, sometimes the difference in some CFTR genes may cause the protein to not be made or not work correctly. When the genetic difference causes a harmful change, it is called a mutation. Cystic Fibrosis is caused when a person inherits two CFTR mutations and lead to minimal or non-working CFTR proteins. Defective CFTR proteins means that cells that produce mucus, sweat, saliva, tears and digestive enzymes are affected and the "bridges" that move sodium and chloride ions in and out of cells aren't doing what they're suppose to do.

When Crosby was screened as a newborn (as all newborns in all 50 states born in hospitals are), they are looking for mutations in the baby's genetic code. This is called gene sequencing. Crosby's CFTR gene was sequenced and he was found to have two mutations in each gene. This means he has a change in each copy of his CFTR genes, one mutation on each chromosome. 

Cystic fibrosis is an autosomal recessive disease. That means a person must have a mutation in both copies of the CF gene to have CF. If someone has a normal CFTR gene and their other gene has a mutation, that person will not have CF but is a CF carrier. Both parents of a child with cystic fibrosis are CF carriers. Lance and I are both carriers. 

Each time two CF carriers have a child together, there is a 1 in 4 chance that both will pass along their CF mutation to their child. Because the child would get two CF gene mutations, the child would have CF. However, there is a 3 in 4 chance that each child will NOT have CF. Children of two carriers may be healthy CF carriers like their parents. It happens like this:

The most common CFTR gene mutation is known as ΔF508. 80 percent of CF patients have a ΔF508 gene mutation and about 40 percent have two ΔF508 gene mutations. There are 23 other common mutations and over 1800 genetic changes have been identified in the CFTR gene. So while a majority of CF patients have this common mutation, lots of CF patients have different combinations of mutations that result in CF. The type of mutation or combo of mutations does not have a direct effect of the severity of cystic fibrosis. This means that even though we know what specific CFTR gene mutations Crosby has, we do not know how sick or healthy he will be.

We have chosen not to disclose which CF-causing mutations Crosby has. I'm doing it for privacy reasons. Probably because I'm an attorney and I've read/am familiar with the Genetic Information Nondiscrimination Act of 2008. But also because I believe that Crosby's genes are personal to him and any information regarding those specific genes needs to be kept private unless he decides to share later on in life.

Crosby's genes will not write his story. Crosby will write his own story. I'm just lucky that I get to be a part of that.

Thanks for reading through this.

Love,

Carmen