LESSON 05: Introduction to atDNA


Here is the easiest version I developed for a recent DNA class I taught.

Current atDNA tests between 600,000-700,000 of the 3 billion SNPS in our DNA. I have wavered back and forth about how to introduce DNA so you really get it and there is no way to do this without taking you through the process. Imagine that you are going to a foreign country for the first time and you do not speak the language. I do not expect you to get all of what I am saying but I hope in showing you the landscape you will pick up bits and pieces that will make more sense to you, once you have a bit of vocabulary and experience. I was trying to explain this to a Genetic Genealogy group online and I came up with this analogy.

Two teenagers don't need to know what you call all the body parts and they may not know exactly how things work---but it is most helpful if they know the consequences of unprotected sex.

In the beginning we have what are called germ cells that become a women's eggs and a man's sperm. The germ cells go through a special type of cell division called meiosis. A major purpose of meiosis is to reduce the number of chromosomes by half. The other is to create genetic diversity. 

Meiosis begins like mitosis: the cell copies each chromosome. But unlike in mitosis, homologous (or similar) chromosome pairs line up and exchange segments in a process called recombination. Remember, homologous chromosomes have the same genes but with slight differences. Recombination increases genetic diversity by putting pieces of slightly different chromosomes together. 

Almost all differences and mutations happen in the germ cells that become eggs or sperm. This is why as men and women age the germ cells that become eggs or sperm have greater and greater odds of replication errors and trisomies. Trisomy like in Down's syndrome is where on chromosome 21 the number of chromosomes was not reduced in half and when combined we get 3 copies of chromosome 21. Some trisomy's result in minor problems and some are life threatening.

Next, the newly recombined homologous chromosomes are divided into two daughter cells. Then the sister chromatids are pulled apart into a total of four reproductive cells. Each of these cells has one copy each of 23 chromosomes, all with a unique combination of gene variations.

Q: So Why do we need to reduce the number of chromosomes in half?

Because if we don't each succeeding generation would double the number of chromosomes.

Q: And why do we need to create genetic diversity?

To insure the survival of the species.

You don't need to remember how this works just that there is a reason that we have recombined DNA.

Now let's take a deeper dive into the double Helix.

Lets untwist the strand of DNA and look at it as if it was a street. Each position on the street, our Chromosome 1, has an "address." One of the most important terms is a SNP. We will think of this as a house. We SNP that House to separate it from the rest of the street.

So we might write this address: Chr 1 5932179.

And at that address we have two "alleles" (or houses one on each side of the street). The alleles are A, T, C, or G. The curvy alleles C & G always pair with each other. And the straight alleles always pair with each other A & T.

At any position we have a pair from Mom and a pair from Dad but only one half of the pair is reported, because we always know that if we have an A it will be matched with a T.

If we look at a readout we might see

Chr 1 5932179 C T

In this case we don't know if the C comes from Mom or the C comes from Dad

But lets look at a longer list from a specific part of the street called a segment (like one block of a long street)

Chr 1 5932179 C T

         5933458 T T

        6000092 A T

        6000117 G A

Look at the numbers are they contiguous? Why not?

First remember that humans DNA is 99.9% the same. So when we look at the results of an atDNA test we are looking at the parts of the DNA that are tested because they tend to have differences. We use the words DNA, chromosome and gene but most folks do not know the difference. So lets take a closer peek without getting too technical. So there are hundreds of SNPS in between the tested SNPS. Some Blocks of the street have lots of SNPS tested and some only a few or none. That is why we have a measurement called a cM centimorgan. This is a unit to describe the genetic distance---looking at the likelihood of inheritance given a certain length of DNA. 

Further explanation

This part of the lesson goes into a bit more detail and will greatly improve your understanding of DNA and therefore help in your understanding of how genealogists use autosomal DNA (atDNA). Please note that this explanation oversimplifies a very complex mechanism. It was originally prepared with assistance from Nancy V. Custer. You may wish to visit her website Contexo for a more thorough treatment.

DNA is a double stranded macro molecule shaped something like a ladder. The familiar double helix:

The sides of the ladder are held together by a series of rungs formed by subunits called a base pair. The four nucleotides which make up the base pairs found in DNA are adenine (A), cytosine (C), guanine (G) and thymine (T). Each rung of the DNA ladder is formed by two paired bases. This pairing is restricted so that A pairs only with T, (straight line letters go together: A & T) and C bonds only to G (curvy line letters pair together: C & G). The value (A,T, C, or G) reported is also known as the allele. There are about 3 billion base pairs in a human.

A gene is simply a short segment of DNA that codes for one specific protein. All of these proteins work inside the cell to perform all the functions necessary for life. Any change in a gene that results in a change in its corresponding protein is called a mutation. Mutations are responsible for the variations among living things.

A chromosome contains many genes: from 379 genes on chromosome 11 to 4,220 on chromosome 1.

Most of the time, chromosomes are invisible even through a microscope. However, as a cell prepares to divide, each chromosome makes a copy of itself and the two replicas remain attached at the centromere (the center of the “X” formation), scrunch up and thicken. When that occurs, the chromosomes can temporarily be seen through a microscope as in the illustration below.

A very nice video that shows the process of meiosis at fertilization is available on the Contexto site here (another meiosis video link below). As DNA is copied and handed down from generation to generation, a small number of “typo” mistakes (mutations) occur. One such mistake may occur when one nucleotide is erroneously replaced by another—for example, the nucleotide cytosine (C) maybe be mistakenly replaced by a thiamine (T). This type of mistake has resulted in variations along the genomes called single nucleotide polymorphisms or, SNP’s. It is these SNPs that are being tested in an atDNA test. Approximately 700,000 to 900,000 SNPs are tested depending on the company.

In the diagram above, the top and bottom DNA double helices represent the results of one DNA strand unwinding and separating with each side serving as a template to build a new complementary side. Two identical daughter DNA molecules are formed, with both having the same sequence. In this diagram a replication error caused the C/G on the top strand to be replaced with the T/A on the bottom. The resulting change in the new strand is a mutation or SNP. In all of human history, about 10 million SNPs (Single Nucleotide Polymorphisms) have occurred.

Let's review starting with the smallest unit and working to the largest.

  • We have four nucleotides: A, T, C and G the building blocks of our DNA

  • The nucleotides form base pairs (AT) or (CG) 

  • SNPs are base pairs where a variation (mutation) has occurred

  • Segments of base pairs that have a specific function are called genes

  • Genes are parts of a very long string of DNA called a chromosome

  • We all have 23 pairs of chromosomes

  • Which reside in the nucleus of our cells

  • All of our cells together form our body

  • The variations and the combination of those variations are what makes each of us unique.

The output from an atDNA test is often called the RAW DNA file. It is simply a list of SNPs and the reported value of those SNPs. Here is an example showing the first few reported SNPs on Chromosome 1:

rsid# (not all positions have an rsid#)
















In this example the rs numbers (rsid) are the name of the SNP, the position where it is located on the chromosome and the genotype  ("AA") is the reported value for that SNP. Occasionally you will have a "No Call" where they were unable to declare what values were there. Ancestry and FTDNA have eliminated many of the medically relevant SNPs so that no information is reported. This involves privacy for those who might have significant inherited medical conditions (see Lesson 13 for more information).

WARNING: Please do not try to print your RAW DNA file. It is over 20,000 pages long!

To give you an idea of what these mutations might mean let's look at the SNPS for lactose intolerance as reported at 23andme.

rs4988235= AA= likely tolerant of lactose (such as found in cow's milk)

r4988235= AG = likely lactose tolerant

rs4988235= GG = lactose intolerant

What this means is that individuals with "AA" or "AG" at SNP rs4988235 are likely to be tolerant of lactose. And those with either "GG" are likely to be lactose intolerant. 

Much of our DNA is redundant so that one replication error does not cause a major problem or one SNP alone does not control for instance your eye color, but the combination of many SNPs. And remember it is these collective differences that makes each of us unique.

It is a good idea to read through this several times before moving on to the next lesson.

More Resources

Contexto's page on Meiosis that includes a nice animation on crossing over.

LESSON 6: atDNA SNPs and segments

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