DNA, SNP, STR, OMG!

(Originally published May 2014 in Going In-Depth)

   Oh my gosh, there are many acronyms in genetic genealogy.  You have to agree that using the acronym DNA is better than writing deoxyribonucleic acid repeatedly.  Although, when we talk about using DNA for genealogy and we only use acronyms, they start to lose their meaning and become just another ‘thing’.  “Hey, I’ve got a SNP.  Do you have a SNP?”  “I dunno, let me check.”  Maybe I’m weird.  I like to understand what all the acronyms mean and how they play a part in the larger picture.

   Let’s start with some DNA basics.  We have DNA in every cell except the red blood cells.  Inside the nucleus of our cells, we have 46 chromosomes or 23 pairs (nuclear DNA).  One set of 23 comes from dad and one set comes from mom.  If we took the tightly coiled DNA from one cell and stretched it out it would be about six feet long.  In that six-foot double helix from one cell, there are over 3 billion base pairs.  If you picture our double helix DNA as a twisted ladder, each rung is a base pair made up from four nucleotides (DNA building blocks).  The rungs are made from either an adenine-thymine rung or a cytosine-guanine rung.

   When we talk about DNA, we often also talk about mitochondrial DNA.  Mitochondria exist outside of the nucleus as an energy source for the cell and have their own independent DNA.  Mitochondrial DNA has just over 16,000 base pairs in comparison to the 3 billion base pairs in our nuclear DNA.  We inherit our mitochondrial DNA only from our mothers.

   DNA is divided into coding regions (genes that define proteins for such things as eye color) and non-coding regions (sometimes called junk DNA).  The coding region that defines us is less than 2% of our overall DNA and within that, there are less than 25,000 genes.  A gene is a sequence of nucleotides averaging about 23,000 base pairs.  One of the largest genes, which encodes for the Caspr2 protein, has over 2.3 million base pairs.

   Within the 3 billion base pairs of our DNA there are variations (normally occurring mutations), where one base pair has been replaced with another base pair.  As an example, it was adenine (A) and now its guanine (G).  This is a single nucleotide polymorphism or SNP (pronounced snip).  There are over 15 million SNPs in our DNA.  Once a SNP occurs, it is usually permanent in the population.  The farther back in time that the SNP occurred, the more people will have that particular mutation.  To be considered a SNP, it has to exist in greater than 1% of the population.  They are found in both the coding and non-coding regions of our DNA.  In the coding regions, SNPs are often markers for genes.

   Let’s divide our DNA into four groups.  Group one, the autosomes, are the first 22 pairs of chromosomes.  The next two groups, the sex chromosomes, are one X and one Y if you are male and two Xs if you are female.  That gives us yDNA and xDNA.  The last DNA group is mitochondrial.  All types of DNA have SNPs.  Autosomal SNPs are used for health and ethnicity.  Mitochondrial and Y-DNA SNPs are used to determine world haplogroups.  While there are 1,000s of X SNPs, there doesn’t seem to be much research around them.

   SNPs have no effect on health, but their presence may predict a health risk.  If you had an autosomal test from 23andMe (prior to the FDA ruling), they would have delivered health information with your results.  They were able to report SNPs in the coding region associated with gene combinations responsible for health risks, like cancer or Alzheimer’s or basic information, like eye and hair color.  Even though you cannot get health information from 23andMe currently, you can still use your autosomal results with Promethease from SNPedia.com to research your health risks.
   Combinations of SNPs are analyzed to determine ancestry-informative markers (AIM – another new acronym for you).  AIMs are used to estimate the ethnicity or at least the geographic origins of your ancestors.  When you receive ethnicity results from an autosomal test, it will be based on the AIMs that the test company are using.  They don’t all use the same markers, so results will vary.  There are even 42 SNPs associated with having Neandertal ancestry.
   SNPs are used to organize us into larger branches of the human family tree (haplogroups).  Our maternal family tree is organized into 26 branches (A through Z) using mitochondrial DNA.  Our paternal tree is similarly organized into 20 branches (A through T) using yDNA SNPs.   As an example, take four men (I use men because the scenario works for both mitochondrial DNA and yDNA), Abe, Bob, Chaz and Dave.  Test each of them for three SNPs, X, Y and Z.  You find that they all test positive for SNP Z, Abe and Chaz test positive for X and Bob and Dave test positive for Y.  You can start to see the branches and the beginning of a tree.

   The first yDNA and mtDNA trees were built using only a few dozen SNPs.  Today, the paternal and maternal haplogroup trees are much more detailed, based on thousands of SNPs.  Complete SNP testing has been available for mitochondrial DNA for a number of years.  Starting last year, complete SNP testing is available for yDNA from companies like FamilyTreeDNA with their Big Y test.  Previously yDNA SNP tests were designed to look for specific SNPs.  With advances in technology, they can now look for all the SNPs across over 12 million yDNA base pairs.

   Just to add another acronym to the pile, there are also STRs or short tandem repeats (aka microsatellites).  STRs are short sequences of base pairs that repeat.  These repeats are found in autosomal, y and x DNA.  You may have heard the term CODIS if you watch Crime/Drama shows on television.  CODIS is the FBI’s Combined DNA Index System (more acronyms).  When DNA is collected for CODIS, they typically test for 13 STR markers across the autosomes.  When you have a yDNA STR test done, genetic genealogy companies test for up to 111 markers only on the Y chromosome.  They will also perform a basic SNP test to identify your paternal haplogroup.  SNPs and STRs are different in that SNPs appear to be permanent changes in our DNA and STRs are variable.  STRs are identified by location on the chromosome and by the number of times that the repeat occurs.  The number of repeats per STR can change over time, sometimes increasing, sometimes decreasing in number or increasing then decreasing again (known as a back mutation).  The combined set of STR markers is your haplotype and may be unique to your surname or span multiple surnames.  With the advances in yDNA SNP testing, SNPs will be found that are unique to your surname, which could make STR testing obsolete.

   We all have DNA: 23 chromosomes in our cell nuclei, half from mom and half from dad.  We also have mitochondrial DNA from our moms.  Less than 2% of our DNA is in the form of genes, which define who we are.  SNPs can be used to identify our “good” and “bad” genes.  SNPs can also help identify our ethnicity and build our paternal and maternal family trees.  STRs can organize us down to the paternal surname level.  When folks start talking DNA, don’t be afraid to question them about, “What kind of DNA?”, “What does that SNP indicate?” or “What type of STR is being tested?”.  We’ll never get away from using acronyms to simplify how we communicate genetic genealogy.  That doesn’t mean we need to let the acronyms simplify the meanings to a point where the science is lost.  Every little bit of knowledge adds to our understanding of ourselves.

© Michael Maglio

Marie Antoinette: DNA Family History

   When we use DNA to research our family history, we have the potential to uncover quite a bit of information.  We could find living cousins, lost connections and deep ancestral origins.  There is also geographic information associated with your DNA.  When you start comparing your DNA to your Clan and your Tribe, you can map your recent old world origins and your migrations.

   You are not limited to your own DNA as you are researching.  As we work on our traditional genealogy, we may find famous ancestors, a Mayflower passenger here or a President there.  If you are descended from them then you can bet that hundreds of other people are also.  Many times one of those hundreds has had their DNA tested to confirm their relationship to that famous ancestor.  You can use that published data to add to your family history.

Source: Wikimedia Commons

   Let’s look at Marie Antoinette, while she has no living descendants, she makes a great example.  Tests from a lock of her hair and from her son’s preserved heart show her mitochondrial DNA to be haplogroup H, the most common group in Europe.

   Marie Antoinette’s results - HVR1 - 16519C and HVR2 - 152C, 194T, 263G, 315.1C

   Marie Antoinette’s maternal line has been documented back 25 generations to the 1100s.  You could still be related to her through this Germanic line of women.  There are twelve exact HVR1/HVR2 matches for Marie Antoinette on Mitosearch.org.  Even with an exact match, that common ancestor lived over 625 years ago, in the 1300s or earlier.

   On paper, Marie Antoinette’s ancestry goes back to the 1100s in the Holy Roman Empire (modern day Germany).  DNA can take us further.  One theory shows a correlation between HVR2 marker 152C and the Goth barbarian tribes.  The Goths were in no way a homogenous genetic group as they grew through mergers and acquisitions.  To say that one DNA marker defines a mixed group like the Goths may be hard to prove.

   If we look at the geographic data associated with Marie Antoinette’s maternal tribe, a pattern starts to emerge.  Take all the DNA records available, matches and close matches.  With each close mismatch, we can step backwards in time in roughly 625-year increments.   TribeMapper® analysis shows a genetic flow of ancestors from Scandinavia down through the Germanic heartland.  The timing of this flow, from 2200 to 1300 years ago suggests a connection to the Goth migrations.  While this is still not definitive proof, it is an additional element that could be used to build a case that Marie Antoinette was a Goth descendant.

   This is an example of the geographic data that can be harnessed from mitochondrial DNA.  The results with mtDNA tend to be more macro as there is less variability, which leads to less timeline resolution.  Y DNA has more variability and will produce maps in greater detail.  Our unique Tribal DNA will tell its own migration story and help tie us to history.

© Michael R. Maglio and OriginsDNA

Is Your Family Tree Broken?

   Non-paternal events (NPE).  There, I’ve said it.  Just how often has it happened in your ancestry?

   Who’s your daddy?  Non-paternal events include – illegitimate births, cuckoldry, sperm donations, hidden adoptions and the use of an alias or intentional name changes.

   The average percentage of non-paternal events if often quoted as 10%.  If you search on the topic, you will find that studies show that 10% is too high.  Keep searching and you will find that in some cultures that number is too low.  Let’s consider the fact that these studies are current day populations and may not represent our ancestors of the last 10 to 20 generations.  These studies also focus on illegitimate or adulterous births.  If we add the events that include adoptions and intentional name changes then 10% is probably safe to use for this illustration.

   Let’s look at your ancestry (or mine) for the last 10 generations.  That is a group of 2046 people, all of them are your direct ancestors.  1023 couples that then gave birth to the next generation.  If we use 10% for NPE, then 102 of those children are not related to those fathers or don’t carry the same surname as their paternal grandfather.   102 of your gggg…grandparents are not genetically connected to their surname.

   If you have done a terrific job of researching your family tree and have the documented birth records for everyone then 10% of the time all you have is a piece of paper.  Your beautiful family tree could just be a pile of fragmented twigs and branches with no relation.  Even if we use an ultra-conservative number like 1% we would still have 10 breaks.  Print out your tree and randomly cut it into 10 pieces.  The piece with your name on it is probably still valid.

   I can hear you now, at least those of you who have stopped crying.  You’re saying, “Ok, I get it, I get it. So, what do I do now?”

   The sands of time have erased everything except your DNA.

   Only through DNA testing, can we ever know for certain that our genealogies are real and not a piece of fiction.  We need to use all the available test types – y-DNA, mitochondrial DNA and autosomal DNA.
If you are male, you are in luck.  You can get all three tests.  If you are female, you can get the mitochondrial and autosomal tests.  Ladies, don’t stop there.  Get your father’s or your brother’s y-DNA.

   To do this right you will need DNA samples for every surname in your tree.  That will not be physically possible.

   Here is a method that will get you many of the surnames.  Naturally, start with your own surname.   Most of us focus on our own immediate surname.  Get dad’s y-DNA and check it against the half dozen DNA databases available and the first thing that you will hopefully find is other folk with the same surname.  Bingo, we have a winner.  My wife’s surname, Clark, has a solid genetic (and paper) line back to 1621.  If I checked the databases and consistently got the surname Brown, then I’d know for certain that I have a break and I would start the process of figuring at which generation the break occurred.

   Let’s assume dad’s DNA went well.  Next get mom’s dad’s DNA and repeat the process.  If that’s not possible, no fear, get mom’s brother’s DNA or mom’s brother’s son or mom’s dad’s brother’s son.  You get the picture.  Here is the added instruction – don’t only get their y-DNA.  Get their autosomal DNA as well.  First, compare your autosomal with their autosomal.   Double check that cousin Bob is really genetically related.  You can’t be too safe with all those NPEs flying around.  Now cousin Bob’s y-DNA can be used to validate that surname.

   While the y-DNA is great for the surname check, don’t forget to use the mitochondrial to test against hidden adoptions.  Every woman in a maternal line should have nearly identical mt-DNA.  Find cousin Sue (you share a gg-grandma Polly) and check that you are related by both autosomal and mt-DNA.  Move out a generation and find cousin Berta (you share a ggg-grandma Molly [Polly’s mother]).  If the autosomal and mt-DNA don’t match then maybe Polly was adopted.

   You should be able to continue these methods with anyone you share a 5th or 6th great grandparent with.  That is 7 or 8 generations out of the 10 we started with (or about 254 surnames) that you could verify with DNA.  The limiting factors at this point are how far back in time the autosomal test will take you and the cost of each test needed.  DNA contributions of a distant ancestor are diluted with each generation.  The current autosomal tests will not get us any further.

   What the past will tell us about the future is that there will be newer DNA tests developed and the costs of existing tests will decrease.

   Start collecting DNA now.  It will only get easier.  Let’s work together to rebuild our broken family trees.

   Happy origin hunting.