THE NUTS AND BOLTS
This lesson 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.
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.
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.
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.
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:
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 SNP for lactose intolerance as reported at 23andme.
rs4988235= GG = likely tolerant of lactose (such as found in cow's milk)
rs4988235= AG = very likely lactose intolerant
rs4988235= AA = lactose intolerant
What this means is that individuals with "GG" at SNP rs4988235 are likely to be tolerant of lactose. And those with either "AG" or "AA" 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.
Contexto's page on Meiosis that includes a nice animation on crossing over.