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.