Orchid offers advanced genetic testing for couples who want their child to have the best shot of a healthy life. “Genetics for Humans” is where we unpack how genetics impacts our everyday lives and the latest tools to help you build a healthier family.

What is a “genetic mutation”?

When most people hear “mutation,” they think of something gone wrong. In reality, a genetic mutation is simply a change in a person’s genome (genetic material present in a cell). Some genetic changes are protective, some are harmful, and most end up not having much of an impact.

Now, mutations can happen in cells from different parts of the body and at different times. Where and when mutations happen matters because it impacts whether that mutation can be passed down to your children or not.

• Mutations can happen “at random” during your life. Say one of your skin cells gets a genetic mutation due to DNA damage from sun exposure. This may impact any future skin cells that came from that original skin cell. But that genetic change doesn’t get passed down to your child because those skin cells with the genetic mutation don’t affect your sperm or egg cells. 
• Mutations can be present since birth. On the other hand, if every cell in your body has that genetic change since you were born, then your sperm or egg cells can also contain those same genetic changes which can be passed down to your children. This is what’s known as a “germline mutation.” 
• ‍Mutations can happen during reproduction. When creating sperm, eggs or embryos, sometimes mistakes can occur during the intricate cell division processes. These can introduce brand new genetic changes to the child not previously present for either parent.

What are the types of genetic mutations that can occur?

Now that we know when and where genetic mutations happen, you might be curious to know how all this can impact you and your child’s health.

On a high level, diseases can be caused by three primary forms of genetic changes: 

1. Extra or missing amount of chromosomal material. Chromosomes are packages of DNA that include many genes — humans typically have 23 pairs of chromosomes. 
2. Genetic mutations in a single gene. We have over 20,000 genes. Some genes are extremely important and harmful mutations in these genes can cause genetic disorders.
3. ‍Many genetic variations in many genes. Most common traits and diseases are caused by changes in many genes all contributing to predisposition for a condition.

Extra or missing amount of chromosomal material can cause conditions like Down syndrome

Oftentimes, extra or missing pieces of chromosomes can happen just by chance during conception. These chromosomal differences can happen in any pregnancy. The most common condition is Down syndrome in which individuals have a third copy of chromosome 21. Individuals with Down syndrome have characteristic facial features, are usually intellectually delayed, and may have other health complications such as heart defects.

However, abnormalities on chromosomes you’ve maybe never even heard of like Trisomy 16 (an extra copy of chromosome 16) can also happen early on in the pregnancy. Since these chromosomal abnormalities are often not compatible with life, these result in early pregnancy loss. Over 50% of early first trimester miscarriages are due to chromosomal abnormalities.

Sometimes, instead of an entire chromosome, pieces of the chromosome are missing or extra. These can be bigger chunks (over 20% of the chromosome) or very small pieces of chromosomal material. These changes can also cause genetic disorders, though the names of these are lesser-known because they are more uncommon.

Genetic mutations in a single gene can cause conditions like Huntington’s disease or cystic fibrosis

In single gene disorders, if one important gene isn’t functioning properly, it can cause a genetic condition. Think about it from a cell’s perspective: every time a cell divides, it needs to copy over all of its genetic material over to the replicated cell. This is no small feat — there are over six billion bases in both copies of the genome. The cell is usually pretty good at doing its job, but sometimes it makes mistakes.

There are many different types of single gene mutations and ways that they can be passed down to impact future generations, but the big picture is that genes encode the instructions for making a protein that the cell needs. A genetic mutation can cause: 

• A protein to not work properly or have reduced normal function. This is often the case for conditions like cystic fibrosis in which there are no functioning copies of a gene. 
• ‍A protein to become overactive or function in a way it normally would not. This is likely the case for conditions like Huntington’s disease in which a mutation in just one of the two copies of a gene causes disease.

Many genetic variations in many genes can impact risk of developing conditions like heart disease

While identifying single gene mutations work for a small handful of genetic disorders, the reality of the genetic basis for the vast majority of diseases isn’t so simple. Instead of finding a needle in the haystack, advanced genetic testing assesses the whole landscape — looking at many genes and genetic markers across the entire genome for each common condition.

When we say assessing the whole genetic landscape — 99.9% of any two human’s DNA sequences are identical. Although a 0.1% difference doesn’t sound like a lot, there are millions of DNA bases throughout the genome that can vary from person to person. These differences change the way a person’s DNA is read and translated into functional protein molecules, each perhaps in a very small way. Together, this can add up to bring about a particular trait.

To predict a person’s chance of developing a common condition, statistical geneticists compare the genetic makeup of tens of thousands of individuals with a particular trait or diagnosed with a condition (“cases”) compared to individuals without (“controls”). This analysis finds many genetic markers that show up more often in people with a particular trait or condition than the general population.

Using large datasets and statistical modeling, researchers are now able to stratify genetic predisposition using genetic scores that incorporate millions of genetic markers across the genome combined. These genetic scores are more predictive for more people than using single gene mutations or lifestyle factors alone.

Orchid offers advanced genetic testing for couples planning on building their family. We use advanced tools and smart, caring humans to help you give your future children the best shot of a healthy life. Conceive with greater confidence and peace of mind