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

Your Autosomal DNA Tapestry

Deep Into DNA*

   What does a tapestry have in common with your autosomal DNA?  A tapestry is a colorful and complex weaving that tells a story.  Your autosomal DNA is a complex weaving of 3 billion base pairs inherited from your ancestors.  Autosomal DNA can tell multiple stories about ethnicity, health and relationships.  As you will see, your DNA can be quite colorful.

Bayeux Tapestry (Source: Wikimedia Commons)

   Every year new tools become available to help us understand our genetic patterns and learn about the stories written in our genes.  There are stories of health issues, both good and bad.  There are stories of our cousin connections.  There is diverse color in our ethnic background.  My autosomal tapestry hangs proudly on the wall.

...continued at The In-Depth Genealogist with a free subscription.


*The Deep Into DNA article series is published each month in the new Going In-Depth
digital genealogy magazine presented by The In-Depth Genealogist.

Pandora's DNA

Deep Into DNA*

   Ah, poor Pandora. So slandered. 

   As the story goes, Zeus gave her a jar and told her never to open it. Pandora’s curiosity got the better of her and she released all the ‘evils’ upon mankind. This is one of many origin stories for why there is evil in the world. This is also a metaphor for the spread or release of information. Too much knowledge can be ‘evil’.

   New knowledge discoveries are often also slandered. DNA test results are a modern example of disrupting the status quo.

...continued at The In-Depth Genealogist with a free membership.


*The Deep Into DNA article series is published each month in the new Going In-Depth
digital genealogy magazine presented by The In-Depth Genealogist.

#gDNA

Testing All Your Genes

Deep Into DNA*

   We all have 46 chromosomes, 23 from mom and 23 from dad. Two of those chromosomes are the sexy kind, X and Y. We’ll ignore those for now. The other 44 chromosomes are your autosomes. Autosomal testing has become available only within the last few years and has become a very popular choice. It offers the broadest range of results, including cousin matches, ethnic proportions and health indicators.

...continued at The In-Depth Genealogist with a free membership.


*The Deep Into DNA article series is published each month in The In-Depth Genealogist Newsletter and will demystify genetic genealogy and make sense out of DNA testing terminology. Each month we will talk about the types of tests available from major labs and show relevant examples on how to use DNA in your genealogy research.

#gDNA

The Autosomal Match Game

   Don’t get me wrong.  Autosomal DNA testing is a very valuable tool.  A match has the possibility of breaking through some very significant genealogical brick walls.  It’s important to understand what a match means or doesn’t mean.

   In a nutshell, we all have 46 chromosomes, 23 from mom and 23 from dad.  Two of those chromosomes are the sexy kind, X and Y.  We’ll ignore those for now.  In an autosomal test, the DNA sequences in your chromosomes are compared against everyone in the testing company’s database.  The goal is to find long matching sequences.  Depending on how long the sequences are and the total number of matching sequences, a calculation predicts the cousin relationship.

   Now here is where things get dicey…

   Take two full siblings (not twins).  At first glance, you might think that genetically they are a 100% match.  Dad gives these two siblings 23 chromosomes each, half of his DNA.  It’s not necessarily the same 23 chromosomes.  Mom does the same.    Let’s look at the two extremes.

   Imagine mom’s DNA as two chunks of 23 chromosomes each – A & B.  Dad has two chunks also – C & D.  Mom gives each child chunk A and dad gives each chunk D.  Both children will have A & D and will be exact genetic matches.

   What if mom gave one child A and one child B.  Then dad gave one child C and one child D.  The full siblings would be A & C and B & D, showing no match at all.  The truth is that a full sibling match will exist on a continuum somewhere in between.

   The probability that a sibling match would be 0% or 100% is extremely low.  Cousin matches are a different story.  In a perfect world, two 1st cousins could share 25% of their DNA.  Two 2nd cousins might have 1/8, 3rd cousins – 1/16, 4th – 1/32 and 5th cousins – 1/64 – a little more than 1% shared DNA.  The possibility of two cousins not sharing DNA or not sharing a long enough sequence to make a match gets higher.

   In my family, two Scottish brothers married two German cousins.  I am the grandson from one of these unions.  I have a cousin who is the grandson from the other marriage.  We are both 2nd cousins and 3rd cousins.  It is possible that we share 1/8 plus 1/16 for a total of 3/16th.  That much shared DNA could be reported on a test as being 1st cousins.

   The autosomal match game is not a perfect world.  If you don’t get a match and you think you should have, then test different cousins.   Adding more DNA samples could give a new set of results.  If you do get matches, the degree of the relationship can help set a starting point in looking for that common ancestor.

   DNA is just one of many tools we have as genealogists.  In the case of autosomal testing, DNA is just the beginning.  It will take traditional genealogy to get you to the prize.

#gDNA

No Father for Rita

   This sounds like a title for an afterschool TV special.  Rita was my grandmother and she was illegitimate.  As in many cases, her McCarthy grandparents adopted her and raised her as their daughter.  I can imagine that her life was in some ways like those old afterschool specials.

   By the time Rita was 5, both of her ‘parents’ were dead and she was now being raised by her ‘brothers’ and ‘sisters’.  I’m relying on anecdotal evidence from my cousins that ‘sister’Helen is really Rita’s mother.   The task of raising Rita fell to Helen’s sister Mary.  Everyone else in the family was out working jobs like – electrician, carpenter, machinist or telephone operator.  The bond between Rita and Mary was tight and lasted until their deaths.  Perhaps I just didn’t see other tight family bonds because the rest of her side of the family passed away before I was born.

Rita (McCarthy) Maglio & Mary (McCarthy) Murphy

   One by one, the McCarthy siblings married and moved away.  By 1930, Rita was living with her mother, Helen, and her new family.  Helen’s husband John listed Rita as a boarder on the census.  As a minimum, Rita should have been listed as a sister-in-law.  My interpretation of this is that John knew exactly who and what Rita was and wanted to distance himself from the fact.  He had no intention of being a father figure.

   Rita was shuffled around to two other families before she married my grandfather in 1938.  Yet, through all that turmoil in her life, she turned out to be the sweetest and most caring of women.

   Whether you are a genealogist or not, you have to wonder who Rita’s real father was.  I do.

   Autosomal testing is one way of determining who he was.  Now I could rely on matching someone randomly in the databases or I could shift the odds in my favor.  I started researching every male in a two-block radius from where Helen was living in 1913.  The research turned up a number of good suspects.  Autosomal testing is not inexpensive.  I needed narrow my field by using any additional evidence I could find no matter how circumstantial.

   One of the single men (not that it had to be an unmarried individual) that I found was just a bit older than Helen was.  Based on my evidence, they probably grew up together and had known each other since they were kids.  When Ed did get married, he named his daughter Rita.  As far as I can tell, Rita was not a common name at the time.  Other folks who were researching Ed posted his photo in their tree.  I thought that there was a bit a family resemblance there.

   I contacted Ed’s descendants and explained what I was trying to do.  They agreed to the testing and then the waiting began.  I expected at least a two-month wait for the results.

   When the results came in, first mine then theirs, I was disappointed to see that against the database I only had potential fourth and fifth cousin matches.  Considering that most folks that are getting an autosomal test are doing it because they are missing big chunks of their genealogy makes finding a common ancestor with a fifth cousin a daunting task.

   Also disappointing was the lack of a match with Ed’s family.  The matching is all done automatically and the results will only show for the close matches.  I even contacted the testing company and asked them to intentionally run a comparison and send me the results.  They did and still no go.  Not even close.

   Still no father for Rita.

   All is not lost.   I have my autosomal results and I have sent out my introductions to all my fourth and fifth cousins looking for a very narrow set of conditions.  They had to have had family at one time in Dorchester.

   The hunt continues.

For more on this family see my posts here & here.

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.  

Mystery Cousins: Autosomal DNA Testing

   I recently received the results of my autosomal DNA test.  The test is part of a larger project that I am working on and not all the other samples have been tested yet.  So, I was happily surprised and confused to find that the results of my DNA matched other people.  I now have 28 fourth or fifth cousins I never knew I had.  These are 28 people with no obvious connections to me.  Not even a surname match.  My first thought was that these are 28 false positives.

Blarney Castle - McCarthy Built

   Everyone has 46 chromosomes, 23 from each parent.  Two of these chromosomes are the sex chromosomes, x and/or y.  The remaining 44 are the autosomal chromosomes.  When comparing the results, the larger the matching segments the closer the relation.  In October of this year, FTDNA announced that they had made changes to their matching algorithm to reduce false positives.  With that in hand, I will move forward with some confidence that these 28 people are my cousins.

   This creates 28 research projects.  Maybe it will be fewer depending on how many of the 28 want to collaborate.  We just have to find our common 4th great grandparent.  No problem, right?

   I should be able to weed out the false positives (if there are any) by getting back to the origins of these other folks.  My 4th great grandparents were either in Italy or Ireland and more specifically, outside of Naples or in the middle of County Cork.

   Some of these 28 ‘cousins’ have also included surnames.  There are quite a few Irish names and no Italian names listed.  This will help narrow the research work.

   I have 28 emails to send – wish me luck.