Wednesday, April 30, 2014

Should I Test My Siblings Also?



A few days ago I got an email from a colleague in California who raised the following issue:

I suggested my brothers each take the AncestryDNA test while its on sale for $79.  One just wrote, "Sis- Didn't you already do this? If so, wouldn't yours and mine be the same?" 

Can any of you give me a quick answer off the top of your head to his question?   

I recall a lecture given by Katherine Borges last year. She showed us that her brother's results WERE different than hers, but I can't remember if it's something that an AncestryDNA autosomal test would catch.

"Celibate" vs "Promiscuous" DNA 

Some of your DNA is passed down to you from one of your parents without recombining with DNA from the other parent. I sometimes call this "celibate DNA." Since it is inherited intact, the information contained in it is identical or almost identical generation after generation. Unless there is a non-parental event (NPE), brothers will share essentially the same yDNA passed down from the father, and all siblings will share essentially the same mtDNA passed down from the mother. Therefore, unless parentage is in question, testing a sibling may be a bit of overkill. Currently in the US marketplace FTDNA is only major company testing celibate DNA for genealogists. 

Other parts of your DNA are recombined with each intergenerational transfer. By a way of contrast I call this "promiscuous DNA." As children inherit promiscuous DNA they get a different information package which is a mix of the contribution of each parent. Some of the information from each parent is lost in the process and some is retained. Into this category I place atDNA and xDNA. 


Autosomal DNA (atDNA)

Three players are active in testing atDNA in the US: 23andMe, AncestryDNA, and FTDNA. Any test you order from the first two will be atDNA tests as will the Family Finder test from FTDNA. Since atDNA is recombined as it is passed down to each child, siblings DO NOT inherit exactly or even nearly exactly the same instruction set unless they are identical twins.

On average the segments of atDNA inherited by two siblings will have a 50% overlap. The range of overlap can be as great as 63% or as low as 37%, but most will cluster near 50%. While this distribution accounts for differing phenotypes among siblings, such as hair color, etc., it also has implications for genetic genealogy.

Two (or more) siblings will not necessarily be shown as matches with the same individuals in a genetic genealogy database. Basically, as more siblings get atDNA results, more DNA matches will be discovered. The inheritance pattern of atDNA is random but there are statistical averages that guide our understanding. You can expect that you will match any close relatives who have also tested and are in the same database. As you look farther back for more distant relatives, the probabilities narrow significantly. You can expect to discover matches with:

  • almost all -- greater than 99% of biological 2nd cousins or those even closer related;
  • about 90% of those who are 3rd cousins;
  • about 50% of 4th cousins;
  • about 10% to 12% of 5th cousins; and
  • less than 2% of more distant relatives.
You will get at lot of very distant cousin matches because your distant ancestors have had so many generations to pass their DNA down to their present day descendants.


Testing Multiple Siblings

The same probabilities of matching cousins who are in a database will apply to each of your siblings who take an atDNA test. However, their probabilities operate independent of yours. For relatives who are 2nd cousins or closer, each sibling will have a high probability of having identical or near identical lists of matches. Each of you will have a greater than 99% probability of matching with any close relatives who are in the database. Testing additional siblings will not do much to enhance your number of matches for very close matches.

My background in math is somewhat in need of verification. As an undergraduate history major, I did take College Algebra. However that is as far as my math education went. I would welcome you readers to correct what I am about to set forth below. I have a feeling that I have the right idea but that I may be leaving out a critical step that will throw off the results.


As you start to look for more distant cousins, the advantages of testing siblings become more evident. At the 3rd cousin level each of you will match about 90% of the actual 3rd cousins in that database. Two siblings would both match about 81%. However, one or another of two siblings would match about 99% of the actual tested cousins in the database. Each would match about 90% of the 10% not matched by their sibling. This would equate to an additional 9% of the cousins in the database for a total of 99%.

At the 4th cousin level each sibling will match about 50% of the actual 4th cousins in the database. Two siblings would match a cumulative total of about 75% of the possible cousins (50% plus 50% of the remaining 50%). A third sibling would raise the cumulative total to about 87.5% (75% plus 50% of the remaining 25%) and a fourth sibling to about 93.75%.

At the 5th cousin level the testing of additional siblings also helps raise the match rate from about 10% for one individual tested to about 19% for two siblings tested (10% plus 10% of the remaining 90%), to about 27.1% for three siblings tested (19% plus 10% of the remaining 81%), to about 34.4% for four siblings tested (27.1% plus 10% of the remaining 72.9%), and so forth.

These numbers are at best approximations. Again, I would appreciate it if some of you could correct any computational errors contained above. However, the clear bottom line is that a much higher number of your actual 5th cousins in an atDNA database -- perhaps more than 3 times as many will be identified if you and three siblings test than would be found if you alone were tested. 

Other advantages of testing the atDNA of as many siblings as possible build on this kind of scale and allow an ambitious genetic genealogist to begin to trace which slice of atDNA came from which relative (chromosome mapping) and other advanced analysis techniques.

Blaine Bettinger points out that if you have been able to test both parents the value of testing all your siblings may be diminished. Especially when examining atDNA, testing the oldest generation possible is always the most desirable. There are fewer recombinations to dilute the information we can find.

Friday, April 25, 2014

Our DNA Day Miracle


Part 2 of a special DNA Day post. If you have not already done so, I suggest that you first read Part 1: Autosomal Dominant Inheritance: Brugada Syndrome


How young should individuals be DNA tested? At 18? Younger? You may recall I discussed Newborn Screening in a post a week ago. How about testing when they get to the 8 cell level? That is typically at Day 3 after the egg is fertilized. This is not science fiction. This is happening now. 

We have bad family planning. Between my wife and I we have 8 biological (plus 2 non-biological) grandsons and NO granddaughters. It almost wasn't like this. For a while we thought we had a legitimate shot at having a granddaughter this time. More about that later.


Brugada in our extended family

You will recall in part one of this post that Brugada, as an autosomal dominant disorder, has a 50% probability of being inherited by any child of an affected individual. In a family with 4 children there is a 1 in 16 chance that the disorder will be inherited by all 4. That is apparently what happened in the family of one of our daughters-in-law. 

The first devastating diagnosis was made when her older brother was in his late thirties. He subsequently had a defibrillator surgically implanted. Soon thereafter my daughter-in-law was confirmed to have the symptom and received a defibrillator as well. Her oldest son was turning 2. At the time the youngest child to have a surgically implanted defibrillator was thought to be 4 1/2. In that case this risky process was performed because he had a younger sibling experience sudden death from such a disorder. My grandson was tested and to all our great relief he had not inherited the autosomal dominant gene. 

When my second grandson was born, my job was to meet my son at the curb outside the hospital and take a blood sample gathered in the delivery room and FedEx it overnight to a lab for testing. Only after this process was underway was I allowed to go inside the hospital and welcome my new grandson. Once again the Brugada bullet had been dodged.

By then we were learning more about Brugada. More comprehensive family testing was conducted. That disclosed the parent who carried the gene and some extended family members who did not. My daughter-in-law's youngest brother was also diagnosed and subsequently had a defibrillator installed.  

With 20/20 hindsight it is suspected that the other sibling of this family also inherited this disorder. He died in 1980 of what was then though to be sudden instant death syndrome at age 2 months. But then we did not know about Brugada. 

When my son and daughter-in-law decided they wanted to have a third child they turned to DNA testing to sidestep any additional Brugada bullets.


Preimplantation Genetic Diagnosis (PGD): the theory


Penn Medicine, The University of Pennsylvania website describes the process of DNA testing at the 8 cell level:
Preimplantation genetic diagnosis (PGD) is a screening test used to determine if genetic or chromosomal disorders are present in embryos produced through in vitro fertilization (IVF). Preimplantation genetic diagnosis screens embryos before they are transferred to the uterus so couples can make informed decisions about their next steps in the IVF process. Embryos unaffected by the genetic or chromosomal disorder can be selected for transfer to the uterus.
 Preimplantation genetic diagnosis is available for couples undergoing IVF. The steps of the IVF process include:
·        Medications are used to suppress a woman's natural menstrual cycle.
·        Her ovaries are then stimulated with medications to produce multiple follicles, each of which may contain an oocyte (egg).
·        The eggs are retrieved from the woman's ovary by a needle placed in the vagina.
·        In the lab, the eggs are combined with the male partner's sperm in a special culture medium that allows fertilization and the growth of high–quality embryos.
Embryo biopsy may be performed after 3 days of culture in the laboratory. The embryos are typically 8-cell embryos on Day-3 and the process involves the removal of one to two cells.After the biopsy and following receipt of the results from the genetic/chromosomal testing, embryo(s) of the best quality that are not affected by the genetic disorder or chromosomal abnormality) are selected for transfer to the uterus. 
The results of preimplantation genetic diagnosis are reported to the couple no later than the morning of their scheduled day for embryo transfer. Typically this is five days after oocyte retrieval and in vitro fertilization are performed. Of the embryo(s) that are not affected by the genetic disorder or chromosomal abnormality, the best quality embryo(s) are selected for transfer to the uterus. If additional unaffected and good–quality embryos are available, they may be cryopreserved for a future embryo transfer.
Preimplantation genetic diagnosis provides diagnostic information based on the analysis of a single cell. Therefore, prenatal testing is still recommended and currently remains the standard of care.

How much does this cost?

One of my stepsons asked my son, "Isn't this process incredibly expensive?" 
My son replied that he had already done a cost-benefit analysis and that the process would cost about half what it would cost to care for a child that carried the Brugada gene.

According to WebMD:
The average cost of an IVF cycle in the U.S. is $12,400, according to the American Society of Reproductive Medicine. This price will vary depending on where you live, the amount of medications you're required to take, the number of IVF cycles you undergo, and the amount your insurance company will pay toward the procedure. 
The cost of an IVF cycle with preimplantation genetic diagnosis is higher.


PGD in practice

My daughter-in-law went through a series of shots to stimulate her ovaries. The result was the production of 28 fertilized eggs. On Day 3 these had reached the 8 cell level of development and were tested. In this case the predicted 50% rate of affected eggs from autosomal dominant inheritance was exactly on target. 14 of the fertilized eggs carried the Brugada gene. Of the 14 that did not, all but 2 were immature or had other abnormalities that did not make them likely to produce a healthy baby. The two that looked the most healthy were both girls.

One of the healthy embryos was implanted. Our daughter-in-law, who is a surgical gynecologist, cautioned us not to get our hopes up because there was only a 35% chance a pregnancy would result. She was prescient. No pregnancy developed so subsequently the second embryo was implanted. Again no pregnancy resulted.

After a decent interval the entire process was repeated. From this cycle only one viable embryo resulted. He was a boy. HE DID RESULT IN A PREGNANCY. And ironically and most appropriately he was born today on DNA Day at Vanderbilt University Hospital here in Nashville! 




My new grandson is not the first child to avoid potential genetic disaster by this type of testing. The first of which I am aware was reported by Oxford University in July, 2013.
A first baby has been born to a couple in the USA going through IVF and involving the use of a new embryo screening approach. The method uses the latest DNA sequencing techniques and aims to increase IVF success rates while being more affordable for couples.
The two babies reported by Oxford University resulted from embryos that were screened at the 5 Day stage.

My grandson was not even the first to be born with the assistance of genetic screening in my daughter-in-law's family. Her brother, the first family member to get a Brugada diagnosis, became a first time father in November after using PGD in the NYC area. However, the young man you see pictured with me is the first of MY grandchildren to benefit from PGD and may have been the first to be born to a woman with a surgically implanted defibrillator -- the fate we are hoping to avoid for her son. 

Autosomal Dominant Inheritance: Brugada Syndrome


This is the first installment of a special two-part edition of this blog to commemorate DNA Day and a grand event that resulted in a special delivery today. Part one describes a serious health threat. Part two, Our DNA Day Miracle, will be an upbeat response to that threat. 


In recent years our family has been introduced to the Brugada Syndrome. The Mayo Clinic tells us, "Brugada (brew-GAH-dah) syndrome is a potentially life-threatening heart rhythm disorder."




The National Institutes of Health (NIH) is more explicit:

What is Brugada syndrome?
Brugada syndrome is a condition that causes a disruption of the heart's normal rhythm. If untreated, the irregular heartbeats can cause fainting (syncope), seizures, difficulty breathing, or sudden death. These complications typically occur when an affected person is resting or asleep. Brugada syndrome usually becomes apparent in adulthood, although signs and symptoms, including sudden death, can occur any time from early infancy to old age. The mean age of sudden death is approximately 40 years. This condition may explain some cases of sudden infant death syndrome (SIDS), which is a major cause of death in babies younger than one year. It is characterized by sudden and unexplained death, usually during sleep.
Brugada Foundation

How common is Brugada syndrome?
The exact prevalence of Brugada syndrome is unknown, although it is estimated to affect 5 in 10,000 people worldwide. 
What genes are related to Brugada syndrome?
Mutations in the SCN5A gene cause Brugada syndrome.
How do people inherit Brugada syndrome?
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition. 


Autosomal Dominant Inheritance

Most of you are familiar with the normal rules of autosomal inheritance. Half comes from the father and half from the mother. At each location on the autosomes each parent, in a seemingly random process, selects for transmission to the child one of the two values each of them inherited from the grandparents (their parents).



In the case of disorders carried by autosomal dominance, the children are affected if they inherit an affected gene from even one parent. Bottom line: each child of an affected parent have a 50% probability of inheriting the disorder. As you know if you flip a coin 4 times, there is a possibility that it will come up heads all four times. Likewise it is possible that the couple in the above illustration will have 4 unaffected children. The odds against that happening are 16 to 1. Those are the same odds that all 4 children will be affected. The most likely outcome, the one illustrated above, is that 2 children are affected and 2 are not. The odds of getting exactly that result turns out to be 6 in 16.

For anyone becoming a parent is a very serious endeavor that involves life changing commitments. For adults carrying a gene for a serious disorder that is inherited in an autosomal dominant pattern, becoming a parent is much more problematic. This situation is compounded by the fact that we are just learning about many disorders like Brugada which are inherited in this way. In the specific case of Brugada, affected individuals may be asymptomatic until they near 40. As a result they may have already made and acted on their decisions to become a parent. Unless the disorder has already been discovered within the family, there may be no advanced warning. 

If Brugada (or another autosomal dominant disorder) is discovered couples wishing to avoid transmitting the disorder now have a cutting edge option. I'll be giving an example of one such case in the second part of this special DNA Day post.

Thursday, April 24, 2014

Dr D FINALLY Joins Twitter


After much prodding from my wife I FINALLY joined Twitter yesterday as @DrDDigs. If you wish to be notified when I make new posts, you can follow me there. I was enticed into creating my Twitter persona so that I would be able to tweet when my special, two part, DNA Day post is ready to announce. I hope the last part of that grand delivery to fall into place by late tomorrow.

Wednesday, April 23, 2014

Sales on DNA Tests


Several companies that test DNA for genealogical purposes are currently offering sales or will be by this weekend.



atDNA Tests

23andMe is currently offering 20% discounts on ADDITIONAL kits after the first when multiple kits are ordered at the same time. This sale is good for those who wish to test several family members. This is an atDNA test.

AncestryDNA is offering a Mothers' Day Sale. It may be a little hard to find but clicking on the link in this paragraph should get you there. It is not clear how long the sale price of $89 will be available for this atDNA test. Buyers are told if they order before May 1st, the kit should be delivered by Mothers' Day.



yDNA Tests

FTDNA is offering two separate sales for a tightly defined period. The sale begins at 12:01 AM CDT on DNA Day, Friday April 25th and ends on 11:59 PM on April 29th. Y-DNA SNPs will be 20% off from April 25 - 29. In addition, the Y-DNA 37 test will be 20% off the retail price. As usual with kits ordered from FTDNA, you may qualify for additional discounts by ordering through a surname or geographic project. Please note that there are two separate tests here. Because these two tests are aimed at different audiences, it is likely that one customer will not be ordering both at the same time. The yDNA 37 STR marker test is a good entry level test for men. It is to test the paternal line which usually corresponds with the surname. On the other hand the individual SNP tests are for more advanced testers who already have some idea about their deep ancestry haplogroup and want to define it more precisely.

YSEQ is also offering individual SNP tests in direct competition with the sale of such tests at FTDNA. Again let me remind you that these tests are not generally for beginners to genetic genealogy testing. The price of $25 per marker "will be in effect until (including) Father's Day (June 15th 2014)."  Thomas & and Astrid Krahn, formerly yDNA experts at FTDNA, are the principals in YSEQ. This price is cheaper per SNP than the sale price of FTDNA. Free shipping is offered on orders of 4 SNPs or more. Buyers will have to consider whether the cost and time of securing new saliva samples for YSEG will offset the difference in the SNP prices. For unusual SNPs one, both or neither lab may currently offer the desired test. There is no simple single solution that will be the best choice for everyone. 


 
So we have two sales for atDNA, two for yDNA SNPs and one for yDNA STRs. Have fun and enjoy the sales. 

Tuesday, April 22, 2014

We Also Collect and Preserve


Yesterday I asked readers if you were a genetic fisher or genetic genealogist. Right after I made that post it occurred to me that there is another important activity for DNA testers. We also collect and preserve or at least we should. 

Oral History

In her awesome keynote at RootsTech in February, The Legal Genealogist Judy Russell reminded us how quickly important pieces of our family histories can vanish. She quoted NARA archivist, Aaron Holt.
“It only takes three generations to lose a piece of oral family history. It must be purposely and accurately repeated over and over again through the generations to be preserved for [future genealogists.]”

She then forcefully drove the point home:
Think about that.Without a real effort to pass down our family stories purposely and accurately, the richness and depth they add to our family history can be lost in just three generations.From grandparent to child to grandchild. That’s just three generations. Things that were absolutely critical in the lives of our own great grandparents — even our own grandparents — could be utterly unknown to us today. 

DNA Test Records

Thomas Jones, also at this year's RootsTech, reminded us that collecting as much DNA from family members -- particularly the older generation -- is as important to preserving our family histories purposefully and accurately as is collecting the oral histories only they can share. Dr Jones suggested that our DNA collection should be limited only by our budgets and that reports of these tests should be preserved for future historians of our families.


Testing Alone Is NOT Enough

Almost all of the DNA testing by our family members has been done in the last decade. Most of it in the last half decade. However, there are already examples in most extended families of close relatives who have tested but are no longer alive. Who has access to the reports of these tests? How long will it be before no one really can interpret those test reports within the context of histories of the families to whom they belong? We may soon be losing access to DNA test reports from family members almost as quickly as we seem to loose access to other family stories.

There are at least two separate and distinct issues at play here. One is physical/digital access the test reports and the other is legal access. Both require purposeful advanced planning.

Do you record the URL, record ID/kit number and password for all of your DNA test reports with your will, trust or other instructions to the administrator of your estate? Why not? Have you spelled out who should have access to these reports? Have you helped family members to document their wishes on these matters?

To my knowledge FTDNA is the only testing company that has acknowledged this ticking time bomb. Filling out this form is not strenuous and does not take a lot of time. So Dr D prescribes you take Nike's advice and Just do it! 



Perhaps The Legal Genealogist can spell this out clearer than I just did. Help Judy!

Monday, April 21, 2014

Are You a Genetic Fisher or a Genetic Genealogist?


There are at least two basic strategies available to those interested in DNA testing to extend their family histories. One is passive and the other is proactive. There is no reason why it has to be either/or.

Genetic Fishers

Most of us probably started as "genetic fishers." We took a DNA test and used our results as bait to "hook" some unknown relatives. As you have probably realized by now, the actual "numbers" on the test reports we get back on our DNA tests are useless for genealogical purposes until they are compared with others and matches are discovered. This is a legitimate strategy. 

To maximize results one needs to fish in the most and the largest ponds their budgets will allow. In the US this would mean doing atDNA tests at 23andMe, Ancestry and FTDNA. Then results should be ported to third part sites like GEDmatch.com to allow cross database comparisons. It would also include taking an mtFull Sequence test and a yDNA STR test of at least 37 markers at FTDNA,    

GENO 2.0 is not a good test for family history fishers because it only begins to comes into focus in earnest earlier than the genealogical time period that most of us can document our histories. Its real purpose is to explore deep ancestry and to preserve the unique genotypes of isolated and aboriginal peoples before they are amalgamated into the mainstream. 

Genetic Genealogists

"Genetic genealogists" are required to use more forethought and often to get involved in active recruiting. It requires the identification of a specific research question which guides the choice of the appropriate test(s) and the person(s) to be tested. My first DNA test in 2004 was to test the hypothesis that another male Dowell, with whom I had been exchanging genealogical information for about 15 years, was closely related and probably shared a common male ancestor during the 17th century. The test quickly disproved that hypothesis. Subsequent testing has established that our closest male ancestor lived more than 3,000 years ago before either of our ancestral lines even dreamed about a taking a surname such as Dowell.

To test other hypotheses it has been necessary to recruit a number of male and female cousins including one that was a 3rd cousin -- once removed and several who were about 6th cousins. Identifying the right cousin(s) and convincing them to test is often more than half the battle. The process of selecting the right test and the right test taker requires an understanding of the 4 inheritance patterns of the 4 types of DNA that I discussed in yesterday's post "Which Ancestors Are Talking?"

Which Are You?  

I suspect that most of us are genetic fishers much of the time. However, I hope many of you will also become accomplished genetic genealogists as well.

Sunday, April 20, 2014

Has DNA Day Lost It's Mojo?



Has DNA DAY lost it's "mojo"? Did it ever have mojo? Did you know that DNA Day is coming on Friday April 25? Did you know that April is or was "Human Genome Month?

This was established by Joint Resolutions of the US Senate and House of Representatives in 2003.



The torch for the US government seems to have been taken up by the National Human Genome Research Institute.

The European Society of Human Genetics has gotten into the act for the last 7 years: 
The structure of the DNA double helix was unraveled over sixty years ago! DNA Day, April 25, is now commemorated internationally as a celebration of Genetics and its promises.
Have I just missed the efforts under way by the genetic genealogy community to take advantage of this educational and promotional opportunity? By coincidence, I will be giving a talk on Friday morning at 9:00 AM to the History and Genealogy Group at the Fifty-Forward Turner Center at 8100 Hwy 100 in Bellevue (TN). The activity is free and open to the public. Have you planned anything in your community?

I still would not be surprised to see a flash sale from one or more of the genetic genealogy testing labs. I also would not be surprised to see a new feature roll out from one of them as well.  Have you heard anything yet? Stay tuned.

Which Ancestors Are Talking?


We all understand that our DNA speaks to us to inform us about the past, the present and the future. As genealogists we are primarily interested in discovering what it has to tell us about our past. To be able to integrate this information with other sources of information, we need to be able to answer two basic questions. What are our ancestors saying and which ancestors are talking?

We will be expanding our knowledge of what our ancestors are saying for the rest of our lives as more and more of the human genome is understood. We can now have a more complete knowledge of which of our ancestors are talking even if we cannot yet fully understand what they are saying. A basic understanding of who is talking to us is one of the first essential building blocks toward becoming accomplished genetic genealogists. 

When we have a genealogical question, we need to be able to understand which parts of our DNA might have information to answer it. Which parts of our DNA give voice to which parts of our ancestors? It comes down to understanding the four unique inheritance patterns of four distinct areas of our DNA. 

By now most of you know that women carry three of these: mitochondrial (mtDNA), autosomal (atDNA) and X chromosome (xDNA). Men carry a fourth kind which I sometimes call "guY DNA" because it is what makes them a guy. If you understand how each of these components of your genome were passed down to you, you have the beginning of an understanding of which ancestors might have something to tell you about your family history. Whole books can and have been written on this subject so what follows below is only a summary of the Reader's Digest condensed version. 

mtDNA

Our mitochondria are not even in the nucleus of our cells. They float around in the fluid that surrounds the nucleus. Some cells contain thousands of copies of our mtDNA information. It has ONLY 16,569 locations. A complete mtDNA test can read the code at each of those positions. 


We all inherit our mtDNA from our mothers and only from our mothers. Men do not pass it on to their children. It is one of the two kinds of "celibate DNA." Celibate DNA is not mixed between with the DNA of the other parent but is passed down essentially intact generation after generation. Therefore it is good for tracing deep ancestry but only along one single line of our pedigree chart. In this case mtDNA would allow us to read information about our mother's > mother's > mother's line back to mtEve. Since it is the smallest "book" in our DNA library it is not a good tool for distinguishing subtle differences between siblings and between descendants of siblings who share a common female ancestor. This is your matriarchy talking without any direct influence from your male ancestors. 

Chromosomes

The rest of our DNA is contained in 23 pairs of chromosomes. 

22 pairs of these chromosomes, the autosomes, share a common inheritance pattern. The two sex chromosomes each share unique patterns. 

yDNA

As you you can see above, the y-chromosome is one of the smallest of the chromosomes. However, with about 58 million base pairs it is humongous compared with our mitochondria. We are still learning how to read the codes stored at most of these locations. yDNA is the other kind of celibate DNA. It generally is passed intact from father to sons generation after generation. It can retain its information for eons because it is not diluted by the DNA contributions of the mothers. However, since male siblings each inherit essentially the same yDNA from their fathers, it generally is not too useful in differentiating between the descendants of brothers. When you listen to your yDNA, it is your patriarchs talking without direct input from your maternal ancestors. 

atDNA

By far the majority of your DNA is contained in your 22 pairs of autosomes. These are one of your two types of promiscuous DNA. In this case their promiscuity is both their endearing quality and the source of frustration as we try to read the information they carry. atDNA speaks to us to help sort out relationships that occurred in the last few generations. Occasionally we get a shout out from an ancestor much further back. However, the apparently random way that our parents pass down the DNA they inherited from our grandparents simultaneously tantalizes and confuses. When you listen to your atDNA, you are most often hearing your ancestors of the last four or five generations ALONG ANY of the lines of your pedigree chart.

xDNA

The other type of promiscuous DNA is xDNA. You inherit it in a manner similar to the way your receive atDNA with one very important twist. Males do not pass along xDNA to male offspring. They pass along yDNA instead. Did I say males do not pass along xDNA to male offspring? Yes I am being redundant. Repetition is the key to learning. Many advanced genetic genealogists have trouble recalling the inheritance pattern for xDNA. If you remember the admonition in this paragraph, you will begin to be able to sort out relationships shared through xDNA. When you listen to your xDNA you will not hear any information from any ancestor who is earlier than a male to male blockage. For example you will not hear any information from your paternal grandfather's quadrant of the pedigree chart because he did not pass any xDNA to your father. This same principle must be applied again and again in other sections of your pedigree chart. 

Which ancestor(s) would you like to talk to today?

Take a look at your pedigree chart. Which ancestor(s) might be able to help you answer a relationship question if they shared the information in their DNA? How did you or a close relative inherit that ancestral DNA? Happy testing and analysis!

Friday, April 18, 2014

Who is our DNA President?


DNA Day is coming next week. Some of the testing companies may offer sales. Who do you consider to be our DNA President(s)?

Many of us know about the role that President Bill Clinton played in encouraging the Human Genome Project. He maneuvered the pubic and private competitors into working toward the same goal and thus expedited the pace of discovery. He even prematurely declared success in this landmark venture so that he could claim it happened on his watch. For this all of us genetic genealogists owe him a debt of gratitude.

On the other side of the political aisle, most of us don't think of George W. Bush as a DNA friendly President. At least I don't usually even though I am related to him at about the 9th cousin level through at least three of his 4 grandparents. Most of us can remember his ban in 2001 on federal funding for the use of new lines of embryonic stem cells in medical research. However, by the last year of his presidency he signed a couple of significant pieces of helpful legislation.

On the eve of President Bush's last DNA Day in office 2008, he signed into law the Newborn Screening Saves Lives Act of 2007:  
The purpose of the `Newborn Screening Saves Lives Act of 2007' is to facilitate the creation of Federal guidelines on newborn screening, to assist State newborn screening programs in meeting Federal guidelines, to improve education, outreach, and coordinated follow-up care, and to improve the laboratory quality and surveillance for newborn screening.
Newborn screening is a public health activity, which provides early identification and follow-up for treatment of infants affected by certain genetic, metabolic, hormonal and/or functional conditions. Since the early 1960s, when Robert Guthrie devised a screening test for phenylketonuria (PKU) using a newborn blood spot dried onto a filter paper card, more than 150 million infants have been screened for a number of genetic and congenital disorders. Screening detects disorders in newborns that, if left untreated, can cause disability, intellectual disabilities, serious illness and even death. Except for hearing, screening tests are done using a few drops of blood from the newborn's heel, usually taken in the hospital 24 to 48 hours after birth. With the advent of the tandem mass spectrometer, it is now possible to detect more than 40 conditions and for some conditions such as PKU, tandem mass spectrometry has been shown to reduce the false positive rate for this disorder.
Parents are often unaware that the number and quality of newborn screens varies from State to State and while newborns are regularly screened and treated for debilitating conditions in some States, in others, screening may not be required and conditions may go undiagnosed and untreated. In 2004, the American College of Medical Genetics completed a report commissioned by the United States Department of Health and Human Services which recommended that, at a minimum, every baby born in the U.S. be screened for a core set of 29 treatable disorders regardless of the State in which he or she is born. At present, only 15 States and the District of Columbia require infants to be screened for all 29 of the recommended disorders. In fact, States currently mandate screening newborns for as few as 9 conditions while others mandate more than 40 conditions. An estimated 1,000 of the 5,000 babies born every year in the United States with one of the 29 core conditions potentially go unscreened through newborn screening. If diagnosed early these conditions can be successfully managed.
The `Newborn Screening Saves Lives Act of 2007' will assist States in improving and expanding their newborn screening programs as well as provide for Federal guidelines on the conditions for which newborns in all States should be screened. The public health crisis that ensued after hurricanes such as Katrina and Rita demonstrated, among other things, that contingency planning for newborn screening is essential. Under this legislation the Secretary is required to develop a national contingency plan for newborn screening for use by States in the event of a public health emergency.
The bill authorized $58,500,000 the first year to carry this activity.

The next month President Bush signed the Genetic Information Nondiscrimination Act of 2008 (GINA) . As most of you know, GINA bans discrimination based on genetic information in making employment and health insurance decisions. It does not protect decisions about life and long term care insurance.


President Bush's actions in 2001 and 2008 appear to be polar opposites. Does anyone have insight into his apparent transformation?

The Newborn Screening legislation takes DNA testing to the delivery room. Soon I will post about taking it even earlier. It's a great story -- at least I think it is. Stay tuned!

Wednesday, April 16, 2014

Power in Projects


I finally got my own BIG Y test results back Monday night. Of the kits I personally am monitoring, 2 kits remain unreported. Those were contributed by my late father-in-law and my distant cousin George. Both of their results pages still project that their results will be available by March 28th. Cousin George has been asked to provide an additional backup sample "just in case" it is needed. I haven't heard anything about my father-in-law's test. That's a little nerve wracking since he is no longer available to provide another sample.

Trying to find meaning in BIG Y results can be overwhelming -- at least at first. I am fortunate enough to belong to a haplogroup R-L21 that has a very active project that is led by some extremely talented leaders who are incredibly generous in sharing their time and expertise. 

I downloaded my raw data Tuesday without a hitch but was a little unsure about the protocol for uploading it to my haplogroup project. BIG Y results are a lot like other genetic genealogy reports. Individual reports by themselves are essentially meaningless. However, they can take on powerful meaning when they are compared with the results of others.

After some investigation I discovered the appropriate way to upload my results to my project. For our R-L21 project which contains several hundred members, the process has been automated by talented volunteer members. This morning, within a couple of hours of uploading the zip file of my raw data, I got an email from James Kane, one of the volunteers:


Hi Dave,

It looks like you are in the S1026 group in case you hadn't already known. You will be in the Big Y Matrix later this morning.

James
James was true to his word. Later this morning I started showing up in various project reports along side six other men who share this SNP. This group will grow as more test takers report their results.

S1026 is one of the new SNPs reported in the last few months by James Wilson of ScotlandsDNA. Context in genetic genealogy is everything. Where is SNP S1026 located? So far I know that it is downstream, more recent, from SNP DF13 which was the most recent SNP for my parental line than I knew about yesterday. All of you reading this, except for 1 or 2, are scratching your heads and wondering what I'm talking about. How about a picture? Thanks to the tireless work of volunteer Mike Walsh I can show you one:


That is S1026 in the small red box at the bottom of the chart. Some of you may remember that a few days ago I discussed the movement of the Virginia Dowells down the SNP trail in the red box on the right side of this chart. On the vertical blue line that appears to bisect this chart, the Virginia Dowells branched off to the right and the Maryland Dowells continued to the bottom of the chart. So far we have been able to track my Maryland ancestors a step closer to the present to SNP S1026. 

Without the dedicated work and amazing expertise of those who lead our projects we would not be able to unravel the messages of our DNA. The haplogroup projects are a very powerful force in helping us learn. 

Friday, April 11, 2014

BIG Y Results Revisited


As I still await my own BIG Y results I continue to explore the results of others to familiarize myself with the test reports. In this post I am examining the report of a man with whom I have long had close STRs matches. His surname is different than mine but the STRs results suggest we share a common direct paternal ancestor in genealogical time.

In earlier testing over the years we had experienced 35/37 matches and 64/67 matches. By 111 STR markers we have 9 mismatches our unadjusted probabilities of sharing a common match according to FTDNA's TiP:


"In comparing Y-DNA 111 marker results, the probability that he and David Ray Dowell shared a common ancestor within the last..."

COMPARISON CHART
GenerationsPercentage
41.74%
827.31%
1267.71%
1690.54%
2097.93%
2499.63%
Since both of us have pretty good paper trails that seem to rule out a common male ancestor within the last 8 generations, we can refine this to run the probabilities again taking this into account:


COMPARISON CHART
GenerationsPercentage
811.54%
1260.70%
1688.49%
2097.48%
2499.55%

We have long ago reconciled ourselves to accept that we do not have a common ancestor on this side of the Atlantic although both of us have deep colonial roots. On the other hand it appears likely that we do share a common paternal ancestor within several generations before our separate departures to the colonies.


As I reported in my first attempt to find genealogical relevance in BIG Y results, I had previously done a single SNP test for DF13 but had not been able to find any more recent SNPs. My STR match had not confirmed that his DNA had progressed down the trail from L21 to DF13. We both strongly suspected that it had but it would be nice to verify this.

Verifying that he was also DF13 turned out to be a little more difficult than I thought. The indexes to BIG Y results did not include DF13 although that SNP has long been in use for the major subdivision of the large R-L21 project and FTDNA has long (at least in genetic genealogy terms) offered a single SNP test for it.

So I turned to a list on Facebook and posted a query asking if there was another name for DF13. Bob Dorr quickly came to my assistance by reposting:
"If you have tested with FTDNA as DF13+, and you search your FTDNA Big YI report for “Known SNPs” for DF13, you will not find it. You have to search for its CTS synonym CTS241 which you will find." from https://groups.yahoo.com/.../conversations/topics/20249  
It then occurred to me that I could have found this information in the ISOGG YSNP TreeCTS241/DF13/S521 are all listed as synonymous there. So many new SNPs have been loaded recently that you may have to give the page a moment to fully load. Then you can use the "Find" feature of your browser to search for a particular SNP.

Mike Wadna soon chimed in on Facebook with this piece of intelligence:
In some cases, the test read quality was low, so it will be marked as REJECTED even though it is derived/positive. The only way I know to check that is look in your raw results. DF13/CTS241's position # is 2836431 and this is the allele change, A to C.
   
So with this information in hand I was able to decoded my match's BIG Y results and determine that he too was positive for DF13/CTS241/S521. I emailed him and said, "So far that was a very expensive individual SNP test you took. ;-)" $495 for BIG Y is considerably more than an individual SNP test for $39.  However, the fun of decoding was only beginning. 

I have subsequently been able to locate BIG Y results for 12 SNPs that have been placed just below DF13 by the R L21 project team. They were all negative for my match who is serving as my temporary surogate. I'm still investigating 2 that had "?" calls and a few more that I have yet to locate in BIG Y. At this point BIG Y is becoming cost effective. Thirteen SNPs tested at $39 each would run $507. Every thing else is gravy. The fun of analyzing BIG Y results is just beginning.  

Even one more step from DF13 downstream to be closer to the present would be very exciting – at least for a couple of hours. Then we would start clamoring for more downstream SNPS!

Hope the thousands of you who ordered BIG Y are enjoying your results.

Wednesday, April 9, 2014

BIG Y: My First Genealogically Relevant Find.


The first thing I learned from the BIG Y test is that the Virginia Group 1 Dowells in our surname DNA project can finally be moved out of the logjam at SNP M222. What? You didn't know that they were jammed up there? Read on.

One of the first things we learned in 2004 in our surname project was that my Maryland Dowells were not recently related to the Virginia Group 1 Dowells. Previously we had assumed that we were closely related. We had our own variation of the multiple brothers myth. I'm sure you have heard a similar tale about one or more of the lines you have researched. 

It goes something like this. Two (or four) brothers came across the Atlantic. When they disembarked one went north and one went west. Which ever branch you descend from never heard from the other branch again. Of course there is enough truth in some such stories that they need to be investigated. However, most of them have remained impossible to verify. One of the Dowell versions I heard decades ago was that four brothers came over from Wales. I still don't know exactly where my Dowells came from before they revealed themselves in Maryland.

Prior to 2004 the working hypothesis among Dowell surname researchers was a variation of the migration myth that claimed upon arrival in Hampton Roads one Dowell turned right and sailed up the Chesapeake Bay and the other continued up the James River. Waterways were the interstate highways of the time so this story had a ring of truth. Based on this story many of us assumed that if either group would be able to extend its paper trail just one or two generations further back, we would find our common male Dowell ancestor.

Then came yDNA testing. It soon became apparent that the two groups of Dowells shared the surname only by historical coincidence. Biologically, we were no more related that we would be if we each had different surnames. Our closest shared male ancestor lived at least three thousand years ago -- long before surnames were adopted. These two groups remain the two biggest clusters in our project. 

SNPs (pronounced "snips") are permanent changes in a person's DNA that are passed down to all descendants. yDNA SNPs are permanent changes that are passed down by fathers to all their sons. As we have learned more about yDNA SNPs, we been able to sketch in more and more of our ancient ancestral lines. The BIG Y test has offered many of us an unprecedented chance to explore our SNP history in much more detail than had previously been available. This is not a test for novices. Even most of us who have considerable experience with genetic genealogy are overwhelmed by the results that are coming back.

Both groups of Dowells descend from a large haplogroup (ancient clan). Membership in this clan is distinguished by a mutation located at position called R-L21. The heat map below is from my results from the Geno 2.0 test at National Geographic which focuses on deep ancestry. The more intense the yellow and finally the red become, the larger percentage of the population carry this SNP. You will note that men who carry it are very prevalent along the Atlantic Coast of Europe and have particularly heavy concentrations in the British Isles.



The chart below shows what we thought we knew about where the two groups of Dowells had traveled down the SNP highway of history before BIG Y. The top of the chart has been truncated for simplicity. It begins as our ancestors migrated out of Central and Western Asia. You will note that L21 is represented by a green box in the upper middle of the chart below. We are very fortunate that a group of dedicated and knowledgeable citizen scientists also belong to the group and have done an immense amount of work to sort all this out. You may click on the chart to open a larger version in your browser. 
   

Before BIG Y we knew that the SNP flow of the Maryland Dowells had continued down to DF13 -- the green box just below L21 above. Then we could find no more recent SNPs. On the other hand the Virginia Group 1 Dowells could be traced through more recent SNP mutations down the left side of the chart to SNP M222. 

This chart was recently expanded to better represent newly discovered SNPs but still does not incorporate the bounty of BIG Y. Note that M222 is now shown among the blue boxes in the center right of the chart below:


The lower right part of this chart (area enclosed by the red rectangle) is blown up below for easier viewing:


Can you trace the path of SNPs from M222 in the fifth row of the family tree down to DF97 in the lower right corner of this last chart? It is sort of a connect-the-dots exercise for genetic genealogists. The Virginia Group 1 Dowells followed that genetic trail. That is what I have learned so far from BIG Y. 

How do I know that? The one Virginia Dowell who participated in BIG Y tested positive for SNPs DF85 and DF97. That means he also would be positive for the intervening SNPs along the connecting line from M222 down to DF97.

I hope we will be able to learn more from the massive amount of raw data that came back from this one test, but this is quite an advancement of our knowledge of the migration of the paternal ancestors of the Virginia Group 1 Dowells. Now we have to put it all into historical context -- a daunting task.

Tuesday, April 8, 2014

Bennett Greenspan is a Pioneer


We now have new evidence that Bennett Greenspan is a pioneer and I unwittingly contributed to it. My blog post yesterday, BIG Y: Open Letter to Bennett Greenspan, was intended to be a tongue-in-cheek piece of humor. Some of my readers took it that way and some of you did not. Could I have written it more skillfully to make my intent clearer? Probably. Am I sorry I wrote it? Not really. Am I sorry it was misinterpreted? Of course. 

Based on reader comments some of you took it for the "Ha-ha!" it was intended to be. Jim Barrett accurately paraphrased my message in three short sentences: 
"I've had recent delays in my life and you've had delays in my results.  I'm about to get mine wrapped up.  I hope you are too!"
Others took it as a criticism of the BIG Y testing program or thought that I was trying somehow to get my results moved up the queue. Nothing could be further from my intent or expectations. If either of these had been my purpose, the reader who commented that I should have kept my comments between myself and Bennett would have been correct. 

It also was not my intent to become a lightning rod for criticism of FTDNA as was the case on one list. There is a proper time and manner for criticism well as there is for praise. We appear to be closing in on one of the latter.

Three pieces of intelligence did come to the fore as a result of my post. I learned that:

  • Considerably more of us jumped at the chance to be part of the BIG Y than had been expected.
  • FTDNA has gone to extraordinary lengths to manage a MAJOR groundbreaking project in an area where few guideposts and benchmarks existed. These have included borrowing an additional sequencer from Illumina.
  • Most of the remaining non-problematic test results may be expected back by next week.

I imperfectly recall a number of sayings I first heard in some version in the middle of the last century that seem to apply to the BIG Y project:

  • The only ones who don't make mistakes are those who don't try anything challenging.
  • Success is biting off more than you can chew and then chewing it.
  • You can always tell the pioneers by the arrows in their back [because they are out in front of the rest of us].

Bennett, yet again, you have given us evidence that you are a true pioneer. The test data from BIG Y reports will give us something to chew on for years. I don't know of anyone else in the world who could have pulled this off for genetic genealogy. I apologize for inadvertently adding to your stress level. It may almost be time to break out the bubbly.