Saturday, June 17, 2017

Unintended Consequence?

We all are familiar with the stated inheritance of autosomal DNA: 50% from each of the parents then about 25% from each of the grandparents and 12.5% from each of the great-grandparents. But how often does it really happen that way? The 50% from each parent part seems to be an absolute. But are the grandparent contributions to our DNA distributed on a "Bell curve" centered on 25%?

When I first started analyzing how my grandsons inherited aDNA from their four grandparents, I only had aDNA results for two of them -- then age 9 and almost 7. I realized that they did not inherit the same amount from each. However, each pair of grandparents contributed 50%. When I was discussing this with my grandsons, the nine year old commented that if we were to test their youngest brother, the almost 3 year old would be more similar to his own than the results of the youngest brother would be with those of middle brother. I previously, posted about these results back in March:

Since I was trying to build their interest in DNA testing, I decided to test this hypothesis. At the very least it would give us a chance to talk about the difference between phenotypes and genotypes. This hypothesis was based on physical appearance--hair, eyes, etc. 

This grandson had already created a minor ripple in the play yard when he was in preschool. He had explained to his classmates the difference between boys and girls using anatomically correct terms. His mother is an obstetrician and had taught her sons the anatomically correct terms for the parts of their bodies. He seemed to be a grandson to whom I could pass on my interest in DNA. 

Toward that end I decided to test his hypothesis about how his genotype would compare with those of each of his brothers. This meant getting cheek swabs from an active boy who by then had just turned 3. The hardest part was to catch the 3 year old when he had not put food or liquid in his mouth for an hour. The swabbing his cheeks part turned out to be relatively easy by comparison.

aDNA of 3 full-brother grandsons received from grandparents
The results for the 3 year old just came back from the lab and his older brother's hypothesis has been supported. In the bar graph above, the 9 year old is in the middle row and the 3 year old in the back. It appears to me that the 3 year old is more similar to the 9 year old than he is to the now 7 year old (in the front row). However, that does not appear to be the breaking news in this chart.

The maternal grandfather contributed only 15% of the aDNA to the 3 year old after contributing 26% and 22% to the older grandsons. In fact the 3 year old inherited more aDNA from his maternal great-grandfather (16.9%) on a pass through among the 35% contribution of the maternal grandmother.

The 3 year old first had his DNA screened before he was implanted into his mother's womb. The purpose of this screening was to bypass a heritable and potentially fatal heart defect carried by the maternal grandfather. I have previously posted about Our DNA Day Miracle. Is it possible that in the process of screening out fertilized eggs that carried the Brugada gene, one was chosen that was an outlier from the normal amount of aDNA that would have been contributed by this grandfather? If so it was an unintended consequence.

Help please!

If any of you have any grandparent to grandchild aDNA inheritance data you are willing to share, please send it to me by instant message or email.

Friday, June 2, 2017

Family Health History

One of the critical building blocks that will enable the new age of personalized / precision medicine will be solid family medical histories. Certified genetic counselors Beth Balkite and Rachel Mills, in their Osher Lifelong Learning course at Duke University this spring, called a good family health history the:

single most important source of information about your future health and risk of illness and your 'free' genetic test.
Understanding Genomics and Precision Medicine:

Balkite and Mills say knowing and sharing information about your family history with your medical practitioners is important because:
Having a first degree relative with a disease can increase your risk for the same disease 2 or 3 fold

First degree relative = parent, sibling or child

Having two first degree relatives with the same disease can increase your risk 5 fold

Similar risks are found if you have other relatives with the same disease
The size of our family health histories will vary. How many first degree relatives do you have? My mother had 16 -- including 13 siblings and 1 child. I had only 4 -- including no siblings and 2 children. Including only first degree relatives is a good start. Collecting and sharing this information is more than most of us do systematically; but including second degree relatives is much more useful and is a much more daunting task.

What is a second degree relative? The simple answer is that it is anyone who is a first degree relative of your first degree relatives. In my example in the previous paragraph, my second degree relatives would include anyone who was a first degree relative of my mother, father and children. My manageable number of 4 first degree relatives explodes to 68 second degree relatives and this does not include the "in-laws" who are not related to me by blood but are to many of my relatives:
  •  4 grandparents;
  •  2 parents;
  •  3 paternal siblings;
  •  4 paternal 1st cousins;
  • 13 maternal siblings;
  • 39 maternal 1st cousins; 
  •  0 siblings; and
  •  3 grandchildren.
This project looks like it is getting totally out of hand. However, if we want to know if something "runs in the family", even more relatives than this may need to be examined.

If you just can't wait to get started charting your family medical history, here are some of the conventions that have emerged from early diagrams tracing color blindness:


Balkite and Mills provide one example of how your chart may look as you proceed through the process:

Of course this is only the beginning. If you want to do all of this online, resources are beginning to emerge that will guide you through the creation process, give you a vehicle for sharing with family and health professionals. They also protect your privacy as you go. These include: My Family Health Portrait; and TapGenes.

Check them out and find one that fits your style. This post is intended only to wet your appetite. You will need all your traditional family history (genealogy) research skills to make this a useful tool as you apply DNA test results in partnership with your health practitioners to use the power of personalized medicine preserve your family's health.

Tuesday, April 11, 2017

California Here We Come!

In early June Denise and I will embark on what has become an annual trip to California. The timing for this is anchored to include the conference of the Southern California Genealogical Society: 
For the last four years this conference has been enhanced by including an all day pre-conference that is focused solely on genetic genealogy. For full details click here:
On that DNA Thursday I will be making two presentations and taking part in another event.

Family History Plus Health History Leads to Personalized Healthcare
Genealogy records family relationships. Health history reveals causes of death, disabilities, chronic diseases, or known genetic disorders within families. How can you build an accurate family health/medical history? Should you? Can genealogists lead the way to personalized healthcare/medicine? Level: Beg., Int., Adv. (David R. Dowell, PhD)
Was Henderson Dowell's Father of African or European Descent?
At Emancipation Henderson Dowell of Wilkes County, North Carolina, was 20 years old and enslaved by Pricilla Dowell. His living descendants are mixed African-American and European-American. Did his paternal ancestors come to America from Europe or from Africa? Level: Beg., Int. (David R. Dowell, PhD)
Meet the DNA Authors
Get acquainted with the authors of recent DNA books. Learn what is covered in each book.
(Emily D. Aulicino, MA); (Blaine T. Bettinger, PhD, JD); (David R. Dowell, PhD)

Friday I get to go from presenter mode to learner mode in an all morning workshop.
Autosomal DNA Chromosome Mapping and Phasing Workshop
This workshop will review ways in which autosomal DNA can be mapped so that DNA segments may be attributed to individual ancestors. Participants will be shown how to begin or continue the process of mapping their DNA. In addition, techniques for phasing their DNA will be demonstrated. Level: Adv. (Tim P. Janzen, MD) Participants need to bring laptops to the workshop loaded with Excel or other spreadsheet program.

Later Friday I get back on the other side of the mike for a panel discussion.
DNA and Genealogy: Experts Discuss Latest Developments
DNA testing experts will discuss the connection between DNA testing and genealogy, what tests are available, and which companies provide which tests. Advances being made in the field of Genetic Genealogy will be examined. Audience questions will be answered in the second half of the program.
Level: Beg., Int., Adv. Moderator: Alice M. Fairhurst, MS, Panelists: Angie Bush, MS; David R. Dowell, PhD; Debbie A. Kennett; Drew Smith, MLS; Diahan Southard

The Family part of the trip

While I am conferring, Denise will be visiting her sister and brother who live nearby. Also on Friday our non-biological grandson, Cameron Adams, will be graduating from San Luis Obispo High School. He also happens to be my 10th cousin -- twice removed. We will also help him celebrate his birthday on Sunday. 

On Monday, in what is becoming an annual tradition, we will meet a group of our former neighbors and friends for lunch at the Great American Fish Company at the T-pier in Morro Bay where the sea otters have been in great abundance this Spring.

Tuesday we plan to have a late lunch with two newly discovered 4th cousins. One of them is a former colleague I have known for years but had no idea we were related until last Fall. The other will be flying in from Texas for the occasion. They are half-sisters who met for the first time in November. For their story see here.

The following morning we will fly back to Nashville exhausted but with many memories to cherish.

Friday, March 31, 2017

Why don't I have as many DNA matches as ....?

It seems that almost daily someone writes on one of the Facebook genealogy sites, "Why don't I match the person that my relative does?" We have the stock answers that include autosomal DNA is inherited in a random manner. Rarely have I seen this so vividly illustrated as in the results of two of my grandsons. In earlier posts the last several days, I have pointed out that each of them inherited different amounts as well as different segments from each of their four grandparents. If this much variation can occur in just two generations, it can really be skewed as it is compounded over four or five generation.

The first of my three previous posts on this subject demonstrated that grandchildren do not inherit equal amounts of atDNA from each grandparent although it appears that each set of grandparents contribute 50%. To review this post click here.

In a follow-up post I demonstrated that these variances of amounts of atDNA inherited by grandchild can alter ethnic predictions between full siblings. To review this post click here.

In yesterday's post I used Family Finder's chromosome browser tool to illustrate how each segment larger than 5 cM of DNA was inherited by each of my grandsons from each set of their grandparents. To review this post click here.

After my post yesterday, Ann Turner asked if I would be willing to do more analysis on the matching segments the two of my grandsons inherited from their four grandparents by dropping the threshold from 5 cM down to 1 cM. In preparing the data to send to Ann for her analysis, I noticed that the two grandsons had vastly different numbers of matches on Family Finder. One had 23% more than his brother. These numbers were not trivial. One had almost a thousand more than the other. How could this be if they were really full siblings?

It largely depends on who is in the database. Groups from different parts of the world are unevenly represented in various DNA databases. The FTDNA database has a disproportionally heavy presence of Ashkenazi Jews. The maternal grandfather shown below has a high percentage of Ashkenazi ancestry. FTDNA has been able to identify about 90% of his atDNA as being of Ashkenazi origin. His number of matches in the database far exceed the number of matches reported from any of the other three grandparents. Conclusion: the grandson who inherited the most DNA from his paternal grandfather will have the most matches in this database.

Grandson #1 below only inherited 22.1% of his atDNA from his maternal (Ashkenazi) grandfather. Statistically normal would be 25%. He did dip into the treasure trove of Ashkenazi results in the database. 18% of his DNA is shown to be of Ashkenazi origins. However, he did not inherit DNA of that origin to the extent his brother did. This grandson inherited 28% of his DNA from his maternal grandmother whose ancestors came from areas of Central Europe that are underrepresented in this database. She currently has less than 400 matches. So the combination of the DNA he inherited from his grandmother (along with her scant matches) and did not inherit from his grandfather was largely responsible for him having over 900 fewer matches than his brother. 

Matching  Relatives

Grandson #1
Grandson #2

Paternal Grandfather
Paternal Grandmother

Maternal Grandfather

Maternal Grandmother


Grandson #2 inherited 26.2% of his atDNA from his Ashkenazi grandfather. That may not sound like a big difference. However it is approximately a 19% increase from the amount inherited by grandson #1.

Even though the maternal grandfather seems to have won the lottery with more than ten thousand DNA matches, his pedigree chart is so short that we cannot yet begin to sort any of those matches into paternal and maternal ancestors.

The paternal grandmother has an extensive pedigree chart; but as yet she has not added it to her Family Finder account.

The mother (my daughter-in-law) seems to have the number of matches that is near the average of her Ashkenazi father and her match deprived mother.

The father (my son) also seems to have the number of matches that is about the average of his parents.

Why do you have the number of autosomal matches that you do?

Thursday, March 30, 2017

Grandsons' DNA continued

Earlier this week I made a free transfer of two of my grandsons' atDNA results from MyHeritage to Family Tree DNA (FTDNA). Since the lab testing for MyHeritage is done in FTDNA's Houston lab, this is a fairly seamless process. As with any new procedure there were a couple of minor obstacles. FTDNA had yet to upgrade the Autosomal Transfers entry icon to mention that MyHeritage kits could also be transferred.

Also, there were no instructions that the "-" needed to be removed from the MyHeritage kit number before FTDNA could be identified and validated. Example: MH-XXXXXX needed to become MHXXXXXX before the transfer could be initiated. These transfers were completed within a few hours and allowed me to use Family Finder's chromosome browser tool.

I was then able to continue my learning process which had begun a couple of weeks ago when I received access to these results at MyHeritage. My previous posts demonstrated that grandchildren do not inherit equal amounts of atDNA from each grandparent although it appears that each set of grandparents contribute 50%. To review this post click here.

I then made a follow-up post in which I demonstrated that these variances of amounts of atDNA inherited by a grandchild can alter ethnic predictions between full siblings. To review this post click here. If these changes sometimes can be observed within only two generations, we can only imagine how they could be skewed over five or six generations of compounded random inheritance. This explains a big part of the differences between ethnicity predictions of full siblings.

On to the Chromosome Browser
Using Family Finder's Chromosome Browser tool, I examined the contributions each set of grandparents made to each of the two grandsons. This process allowed me to visualize things I sort of knew intellectually:

  • Each set of grandparents combined to pass down 50% of the grandchild's atDNA but the grandparents within each set did not contribute equal amounts;
  • Each grandparent's contribution to full siblings differs -- sometimes in measurable amounts;
  • There really are two different strands of atDNA inherited by children -- one from the father and one from the mother;
  • We can visualize the "crossovers" on the paternal and on the maternal strand of atDNA inherited by the grandchildren and thereby trace which part of the grandchild's atDNA was inherited from each grandparent; and
  • Grandsons do not inherit any xDNA from their paternal grandparents.

Maternal grandparent contribution
In this image the atDNA contribution of maternal grandparents are charted for grandson #1. Note that xDNA was inherited from the maternal grandparents through the child's mother. In this case about 28% of the grandson's atDNA was inherited from the maternal grandmother (represented by the orange bars). About 22% came from the maternal grandfather (represented by the bright blue bars). Crossover points are clearly visible where the contributed atDNA shifts from the maternal grandmother to the maternal grandfather on this maternal contributed strand.
In this image the atDNA contribution of maternal grandparents are charted for grandson #2. Note that xDNA was inherited from the maternal grandparents through the child's mother. In this case about 26% of the grandson's atDNA was inherited from the maternal grandfather (represented by the orange bars). About 24% came from the maternal grandmother (represented by the bright blue bars).

Paternal grandparent contribution

In this image the atDNA contribution of the paternal grandparents are charted for grandson #1. Note than no xDNA was inherited from the paternal grandparents through the child's father. In this case about 28% of the grandson's atDNA was paternal grandfather (represented by the orange bars). About 22% was inherited from the paternal grandmother (represented by the bright blue bars).    

In this image the atDNA contribution of the paternal grandparents are charted for grandson #2. Note than no xDNA was inherited from the paternal grandparents through the child's father. In this case about 26% of the grandson's atDNA was paternal grandfather (represented by the orange bars). About 24% was inherited from the paternal grandmother (represented by the bright blue bars). 

Ashkenazi Origins

One other item of interest to report came out of this exercise. Family Finder identified more Ashkenazi DNA from both grandsons than did MyHeritage. One grandson appears to have inherited about 22% of his atDNA from his primarily Ashkenazi grandfather. No other grandparents have been shown to have any Ashkenazi inheritance. Family Finder Identified about 18% of this grandson's atDNA to be Ashkenazi.

The other grandson appears to have inherited about 26% of his atDNA from that Grandfather. Family Finder identified about 21% of this grandson's atDNA to be of Ashkenazi origin.

MyHeritage had identified  the first grandson to have 10.8% Ashkenazi and the second one to have 17.5%.

Saturday, March 25, 2017

Ethnic Origins Predictions Affected by Random Autosomal Inheritance

Predictions of our ethnic origins are one of the biggest draws to get people to order a DNA testing kit. Almost all of these predictions are based on our autosomal DNA. That's the only DNA tested by Ancestry, 23andMe and MyHeritage. Family Tree DNA offers these predictions as part of its Family Finder test results. Marketing surveys suggest that more more than half of millennials who take genealogy DNA tests are doing it only or primarily to find out whether they should be wearing kilts or lederhosen to the next family gathering. 

In spite of the warnings of prominent genetic genealogists that these projections at present are one of the softest parts of the science of genetic genealogy, the advertising seen on television and elsewhere continues to emphasize predictions of ethnic origins. 

The Legal Genealogist, Judy G. Russell, is one of the most outspoken critics of the credibility of the predictions we are given. In an August 14, 2016 blog post "Those Percentages, if you must", she reiterated:
The Legal Genealogist says that the ethnicity estimates part of autosomal DNA tests are not a whole lot more than cocktail party conversation,
It just doesn’t seem to matter.
You can’t rely on DNA tests to give you exact percentages of your ethnic origins beyond the continental level (European, versus African, versus Asian).
Judy's conclusion is a valid one. Part of the problem is that this part of our science is still immature: 

  1. The population geneticists really can't tell us where all of our ancestors were living 500 years ago;
  2. Very few of us have pedigree charts that inform us about who all of our genealogical ancestors were in 1500 and where they resided; 
  3. Although atDNA tests generally sample 500,000 to 700,000 locations to make these ethnic predictions, this is a small percentage of our entire genomes; AND   
  4. Inheritance of our atDNA is random.
We all know that we inherited 50% of our atDNA from our fathers and 50% from our mothers. But how many of us know how much of our atDNA we inherited from our maternal grandfather? Would this make a difference in our predicted ethnicity? Of course it would.

Last month I published results from atDNA tests taken by two of my grandsons at MyHeritage. They are full siblings. Their other grandfather is primarily Ashkenazi. His Family Finder origins prediction is shown below. 

None of the other three grandparents show the presence of any Ashkenazi genetic component in their Family Finder results. My daughter-in-law was reported in her Family Finder results to be 42% Ashkenazi. [23andMe reported 48%.] Although I am not comparing apples to oranges in this post, I may be comparing different varieties of apples to each other by comparing testing results from three different companies. However, different family members have tested at different companies. These cross testing companies comparisons should not effect my main point in this post. If you have data that would dispute that, please share and we all will learn something.

My main point is that my grandson who appeared to inherit only 22% of his atDNA from his Ashkenazi grandfather in my previous post, was shown by Family Finder to have significantly less Ashkenazi ethnicity than did his full sibling who appears to have inherited 26% of his atDNA from that grandfather. 

This is an extremely small sample and the results may be distorted because results from different companies are being compared. However, I encourage you to try this at home if you have test results reflecting the difference between the atDNA inheritance patterns of sibling grandchildren. The result I report above is in accordance with what common sense would lead me to believe. If you have results that would support or refute this tentative hypothesis, I would love to see it. Maybe we all will learn something.

Saturday, February 25, 2017

Grandsons' atDNA Inheritance: A Case Study

If you are familiar at all with genetic genealogy, you know that children inherit 50% of their autosomal DNA (atDNA) from their mother and 50% from their father. You also may know that while children inherit about 25% of their atDNA from each grandparent, these amounts may vary.

I recently had the opportunity to compare the amount of atDNA shared by two of my grandsons with each of their four grandparents and with one great-grandparent -- father of their maternal grandmother:

G-son A 1852.9 cM 1731.5 cM 1882.2 cM 1719.8 cM 727.2 cM
25.8% 24.1% 26.2% 23.9% 10.1%
G-son B 2025.7 cM 1558 cM 1584.9 cM 2017.4 cM 885.4 cM
28.2% 21.7% 22.1% 28.1% 12.3%

As you can see above, the percentage actually shared by each grandson with each grandparent varied from 21.7% to 28.2%. No big surprises there. We have long been told that after the first generation the amount of atDNA inherited is somewhat random and varies from one grandparent/grandchild pairing to another.

Note also that the amount inherited by both grandsons decreased by more that 50% between the amount they inherited from their maternal grandmother (M-GM) and her father (M-GGF). In this case the decrease seemed to be in proportion to the amount they had inherited from their maternal grandmother but I don't think we can come to any solid conclusions from this very small sample.

One thing did jump out at me that I had never though about before. As I mentioned above, it is well known that all children receive 50% of their atDNA from each parent. However, it had never occurred to me that all grandchildren inherit 50% of their atDNA from each pair of grandparents. While the amount inherited from each of the four grandparents may vary considerably, the amount inherited by the maternal grandparents combined or from the paternal grandparents combined will add up to 50%. It is a logical conclusion but not one that I had thought about before.  

Now I'm pondering to what extent this principle can be extended. For example, can we calculate how much atDNA my grandsons may have inherited from the mother of their maternal grandmother (M-MG). Can we conclude that each of the grandsons inherited 25% combined from the parents of their maternal grandmother? That would be useful, if true, because we only have DNA test results from one of the great-grandparents.

I'm still pondering how far, if at all, this bonded inheritance can be extended. Do any of you have data and/or thoughts? 

Saturday, February 11, 2017

The Winning Innovators for 2017 Are

Last year a big portion of the $100,000 in cash and in-kind support from the Innovation Showdown at RootsTech 2016 went to TapGenes which has continued to develop its product and outreach for those seeking to organize and share family health information. 

This year 40 contestants from the US, Europe and Canada entered the competition. Ten semifinalists were invited to compete this week in Salt Lake City during  the world’s largest family history technology conference. In case you want to look back at those semifinalists now, you can look at my earlier post where the ten are listed with links to where you can find more information.

Judging focused on both the promise of the product as well as the soundness of the business model. Each contestant had two minutes to present the product. Then the panel of five judges had a combined two minutes to ask questions or make comments. If you are familiar with the television show Shark Tank on ABC, you should be able to visualize this format. 

Although the originally announced prize pool of $100,000 in cash and in-kind support was impressive, three new sponsors emerged and enabled the awards to swell to almost twice that amount. The new sponsors were Amazon Web Services (AWS), Kickstarter Seed Fund and Sorenson Legacy FoundationFriday the five finalists competed before a live audience and those watching via streaming around the world. Both those in Salt Lake City and those streaming were able to text their choices. Interestingly, the people's choice and the judges choices were different.

2017 RootsTech Showdown Winners

  • First Place Judges’ Choice ($90,000 cash, AWS credits, and an investment from Kickstart Seed Fund), Bill Nelson of OldNews USA.

  • Second Place Judges’ Choice ($44,000 cash and AWS credits), The Qroma tag mobile app for embedding stories into pictures, tagging them by voice commands, and making the data accessible on various platforms.
  • Third Place Judges’ Choice Award ($26,000 cash and AWS credits), Louis Kessler, Double Match Triangulator, an app to help sort autosomal DNA matches into groups of relatives.
  • People’s Choice ($25,000 cash and AWS credits), Kindex, an app designed to help users create searchable, shareable archives of family letters and other documents using tags to help users easily locate information.

  • The distinguished panel of judges were: 

    Kenyatta Berry, Co-host of The Genealogy Roadshow
    Al Doan, Co-founder and CEO of Missouri Star Quilt Company;
    Thomas MacEntee, Founder of High Definition Genealogy;
    John Richards, Founder and CEO of Startup Ignition; and
    Dalton Wright, Partner in Kickstart Seed Fund.

    More information about the awards competition can be found in the press release.

    Keep in mind that the overall winner may not be the new product that will be the one most useful to you in your research.