DNA testing is revolutionizing personalized medicine and the way we appreciate our ancestry and genealogy.   A very common question is “What is DNA and how does my DNA function?”.  To understand how genetic testing works, let’s take a look at the structure of DNA and how information is encoded in the DNA structure used by your cells.  DNA is a bit like an onion – the basics can seem simple, but there are many layers once you explore further.  By learning about the structure of DNA, you will be able to understand how your genes work and interpret the results of any genetic testing you might receive.

What is DNA? 

DNA definition:

DNA stands for deoxyribonucleic acid and is the blueprint for the human body.  The human body contains billions of cells and each one holds DNA that tells the cell how to work.  Your DNA is like a book that tells your cells a story on how to make your body.  Each letter in your DNA book is called a ‘nucleotide’.  There are four types of DNA that compose the nucleotides:

  1. Adenine
  2. Guanine
  3. Cytosine
  4. Thymine

The image below shows the double helix, the DNA structure used by your cells to encode genetic information.

What is DNA? Looking at DNA structure and DNA function to help understand DNA testing.

DNA structure: DNA is stored as a long strand within the nucleus of each cell.  Large pieces of your DNA are called chromosomes which contain a very long DNA strand composed of nucleotides that basepair to form a double helix.

These four nucleotides are the building blocks of DNA.  Each nucleotide has a slightly different molecular structure that makes one look different from another.  Your body has small biological machines called proteins that can sense these differences and use them to understand the instructions contained in your DNA.

DNA Structure:

What is the DNA double helix?

In the figure above you can see the DNA structure used by cells to encode genetic information.  For DNA to store data, different nucleotides combine into a very long DNA strand.  The strand of DNA is just a very long chain of nucleotides combined together in a line.  Two strands of DNA come together to form the famous DNA double helix.  The double helix is useful for your body because it is very stable (DNA can last for millions of years) and having two strands in the double helix acts as a back-up – if one strand breaks, your body can still use the other strand to fix your DNA!

What is a chromosome? A DNA structure used to compact all your DNA into a very small space:

Did you know that each cell in your body contains about 6.4 billion nucleotides of DNA?  We call the total combination of all the DNA in a cell ‘the Human Genome’.  Although DNA is very small, 6.4 billion nucleotides is a huge number.  If you stretch out all the DNA strands in one cell, the total length is about 6 feet or 2 meters!  Amazingly, if we combined all the DNA from all of the body’s cells (trillions of cells), that DNA would stretch all the way to the sun multiple times over!  To package all of this information into the small space of a cell, your body creates a very compact DNA structure called chromosomes.  If the human genome is a book, then the chromosomes are the chapters.  Your cells have very specialized machinery that packages up your DNA into small, well compacted chromosomes.  For humans, there are 23 different chromosomes and each cell has two copies of each chromosome.  We have two copies of each chromosome so that we have a backup copy in case something goes wrong.  In total, there are 46 chromosomes in each cell.

What is DNA? Image of human male chromosomes via DNA testing of chromosomal DNA structure.A picture of DNA structured into chromosomes: The results of a DNA test called a ‘karyotype’ that was run on my DNA isolated from white blood cells.  Karyotyping is used to analyze the chromosomal DNA structure present in your cells. You can see each of the 46 chromosomes in my genome. I have two copies of the first 22 chromosomes, one X chromosome and one Y chromosome.  

In the picture above we are actually looking at my DNA.  This is a picture I took using a microscope after isolating the chromosomes from my white blood cells.  This type of picture is called a karyotype, and is used in genetic testing to detect large DNA structure changes called “chromosome abnormalities”.  You can actually see changes in the DNA by just looking at it under a microscope!  Surprisingly, I am quite normal at the DNA level.  You can see in the picture that I have 46 chromosomes – and then one X chromosomes and one Y chromosome.  This means that I am a relatively ”normal” male at the DNA level.  Isn’t it amazing how different each of the chromosomes are?  They actually vary quite a bit across different people, even siblings and twins.  Learning to visually identify and interpret changes in DNA using a microscope requires intensive training – there are specialized doctors called cytogeneticists who study for years to help diagnose people with DNA structure changes and chromosomal abnormalities.  If you’re interested in the different types of DNA testing, take a look at the three different types of DNA test kits you can order at home (spoiler – karyotyping like what we see above isn’t one of them).

Now, let’s talk about the different types of chromosomes.

The 23 Chromosomes (and the basis for 23andMe’s company name):

The first 22 chromosomes are called autosomes, and both men and women have the same set.  The 23rd chromosome is called the “sex chromosome” because there are two different versions that vary based on your gender:

  1. The X chromosome
  2. The Y chromosome

These chromosomes determine your gender.  If you have two copies of the X chromosome, your cells will interpret the DNA to make a female body.  If you have one copy of the X chromosome and one copy of the Y chromosome, your cells will decode the DNA and make a male body.  The number 23 is used by 23andMe because this is the number of different chromosome types in the human genome.

Where Did My DNA Come From?

Interestingly, you get one chromosome from each of your parents.  Figuring out which parent donated the X and Y is easy to determine for boys.  In males, the X chromosome comes from mom and the Y chromosome from dad.  Looking at the picture of my DNA above, the X is inherited from my mom (hi Mom!) and the Y from my dad (hey Dad!).  For the autosomal chromosomes and in girls (who are XX), it is harder to determine the origin of each chromosome – we need to run sophisticated DNA tests called DNA genotyping or DNA sequencing.

We’ve now covered the basics to answer “What is DNA?”.  Now, let’s take an in-depth look at how DNA functions.

The Function of DNA:

The DNA code:

We’ve looked at the question of “What is DNA”.  But how does DNA function? DNA is the blueprint for the human body and all forms of life  detected so far – even viruses use DNA or another similar molecule called RNA!  You can think of DNA as a book full of instructions, but these instructions have to be interpreted somehow.  The process of using the information contained in DNA is called the “central dogma.”  This sounds complicated, but is actually quite simple.

The central dogma of genetics helps answer what is DNA by showing DNA structure and function .

How DNA functions: The unique double helix DNA structure enables the information contained within your DNA to be decoded by converting it into mRNA via a process called transcription.  The mRNA is then expanded into many different protein molecules to do most of the work in your cells. 

The Central Dogma

There are two parts to the central dogma:

  1. DNA transcription: Decoding the information in DNA to make lots of mRNA.
  2. mRNA translation: Translating the mRNA into protein.

Our cells use the central dogma to decode DNA and make lots of little biological machines that are called proteins.  We go through a two-step process to make proteins because we need so many proteins for our cells to work.  Your cells only have two copies of each chromosome, but need millions of copies of each protein!  So, we take our DNA and expand it into many copies of mRNA via a process called transcription.  mRNA is then translated into proteins, which act as machines to do most of the work in your cells and body.  You can think of the DNA code and the central dogma as a process of signal amplification – we take two copies of DNA and amplify the information to make millions of tiny machines called proteins.

Genes – The sentence of the human genome:

In writing, we want each sentence to have a specific purpose or thought.  Our DNA is organized in a similar fashion but instead of sentences, our cells use genes.  Each chromosome can contain millions of nucleotides of DNA arranged in a long string.  These long strings of DNA are then divided up into sub-regions called genes.  If each nucleotide is a DNA ‘letter’, then your genes are the sentences in your DNA.

Let’s move on in our mission to answer the question of “What is DNA” – The next thing we need to understand about DNA is the different parts of the human genome that exist in your cells.

The Human Genome:

It took scientists decades and $2.7 billion dollars to sequence the first human genome as part of the NIH Human Genome Project.  One of the interesting things that we learned by sequencing the human genome is that most of our DNA is not actually used for genes that make protein.  Out of the 6.4 billion nucleotides in a human genome, only about 2% is dedicated to protein coding DNA!  The other 98% is used to control when a gene is on or off.  We call this “other” 98% of the genome the non-coding or regulatory DNA.  The secret around the protein-coding DNA was finally understood by the NIH scientist Dr. Marshall Nirenberg who won the 1968 Nobel Prize in Medicine for decoding DNA (he shared the prize with Dr. Har Khorana and Dr. Robert Holley).  Remarkably, the NIH has contributed to understanding DNA code, and then decades later led the project to sequence the human genome.

The composition of the human genome has an important impact on clinical genetics and DNA testing.  We can divide the genome into two parts.

  1. Protein coding DNA: This part of your genome makes proteins and has a unique code that was “broken” in the 1960’s. A human can understand the code and the impact of coding DNA changes can be predicted by a doctor trained in genetics.  Roughly 2% of your genome is “coding DNA”.
  2. Non protein-coding DNA: This part of your genome contains the instructions that tell your body when to turn a gene on or off. There is a code in this part of your genome, but scientists do not understand it.  It is very hard to predict the clinical impact of changes in the non-coding DNA.  Roughly 98% of your genome is non-coding DNA.

Almost all genetic tests will analyze only the protein coding DNA.  Interpretation of non-coding DNA is currently an active area of research at the NIH and many other clinical genetics laboratories.

DNA Variants: What Makes Your DNA Unique

The first human genome that was sequenced is now called the “reference genome,” and there is a special group of scientists who constantly work to make the reference genome better (the NIH NCBI Genome Reference Consortium).  The current reference genome is now called hg38 and is composed of DNA sequence data from multiple individuals.  You can think of the reference genome as a map – it tells us where all the genes are and what DNA sequence to expect at any position in the genome.

In 2018, the material cost to sequence a human genome is about $850.  That is a remarkable drop in price driven by NIH basic research funding over many decades!  (See the NIH/NHGRI page on sequencing costs for the human genome for a great overview on how cheap DNA testing has become)  The most difficult part in DNA testing and molecular diagnostics is no longer DNA sequencing – it is the interpretation of what a change in a DNA sequence means for a patient’s health.

When we sequence a human genome, we expect to find about 4,500,000 changes between the person being tested and the reference genome.  Each change is a point where the genome is different from the reference genome that was already sequenced.  We call each change a variant.  If you get a DNA test, you will receive a report on all the points where your genome varies from the reference genome.  There are three types of DNA variants:

  1. Pathogenic variants: These variants change the DNA in a way that breaks how the cell functions. A pathogenic variant is typically very rare and is associated with human disease.
  2. Benign variants: These variants change the DNA in a way that does not significantly change how the cell functions. Most DNA variants are benign and are not associated with human disease.
  3. Variants of unknown significance (VOUS): These variants change the DNA in a way that scientists do not yet understand.  Because we are only starting to decode the human genome, we do not yet understand the result of all DNA variants.  A VOUS variant means that the predicted impact of a DNA change is unknown.

The process of determining the impact of a DNA sequence variant on a person’s health is called variant classification.  Variant classification requires extensive expertise in molecular biology and human genetics – doctors who specialize in understanding and interpreting human DNA sequence variants are called clinical molecular geneticists.  Clinical molecular geneticists are PhDs and MDs who have undergone years of specialized medical training overseen by the American Board of Medical Genetics and Genomics.

In the old days, pathogenic variants were also called DNA mutations.  A mutation was typically seen as a rare variant that causes human disease.  In modern clinical genetics we have switched to the term pathogenic variant because it is more specific.

Sometimes you will run into a DNA sequence variant called a polymorphism.  In clinical genetics, a polymorphism is a variant that occurs frequently across many people.  Typically, a polymorphism is defined as a DNA sequence change that is seen in at least 1% of a population.  This means that if we sequence 100 people and compare their variants to the reference genome at least one person will have that particular DNA sequence variant.  Because genetic disease is very rare and DNA polymorphisms are common, most polymorphisms will be benign variants.

Conclusion – What is DNA? Wrapping up our look at DNA structure and function.

As you can see, answering the question “What is DNA?” isn’t a simple task.  We’ve now reviewed the basics of DNA structure and analyzed the function of DNA to understand how DNA works.  We’ve also covered the different types of DNA variants that can be found by DNA testing.  If you’re interested in DNA testing and thinking of ordering an at-home DNA test kit, take a look at the most important factors for you to consider about 23andMe and Ancestry.com testing.  For more details about clinical genetic testing, take a look at an overview of clinical testing and the type of information it can return.

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Drew Michael, Ph.D.
Dr. Drew Michael is a Clinical Molecular Geneticist and Clinical Biochemical Genetics fellow. He holds a Ph.D. in Molecular Cell Biology and an M.S. in Biochemistry and Molecular Biology. Dr. Michael has an extensive background in molecular and computational genomics and runs a research program designed to understand the gene regulatory programs which control human development and disease. His diagnostic research is focused on the molecular and biochemical diagnosis of rare human diseases. Outside of science and medicine, he really likes dogs and lives in Washington, D.C. with two german shepherds.