Thursday, April 21, 2016

DNA Day Sales & a Birthday Party




Many of you know that we celebrate DNA Day on April 25th to commemorate the 63rd anniversary of the publication of the Nature article that detailed the structure of DNA. It's a little late to enter ASHG's DNA Day essay contest this year, but you still may want to contemplate your own response to the assigned topic. Read the next paragraph before you guess what my position might be. 

A few of you may know that this day has a special significance for the Dowells of Nashville. It will be the 2nd birthday of our 2014 DNA Day miracle. Benjamin was born 9 months AFTER he had part of his DNA screened to select a healthy fertilized egg that did not contain his mother's heritable mutated and potentially deadly Brugada gene.



DNA SALES!!!

To help us celebrate Benjamin's 2nd birthday this weekend, at least two of the big three US DNA labs are having sales from now until April 26th.


1. Last night CeCe Moore spread the word about the DNA Day sale at AncestryDNA 
- $79 and free shipping if you use the FREESHIPDNA code -
DNA.ANCESTRY.COM


2. 10 AM Central time today is the kickoff of a big DNA Weekend sale at Family Tree DNA



Ancestry's sale price is for the only product in the company's line of DNA tests. FTDNA's sale includes many but not all of the company's tests -- some of them discounted more than they often are during sales. 

I'm going to a 2 year old's birthday party this weekend dressed as -- (did you guess it?) -- a carnival barker.

So come one, come all and let the spitting and swabbing begin!! 


Sunday, April 17, 2016

My 10th great-grandfather is my 9th great-grandfather?



I was stimulated to write this post by reading Lara Diamond's blog today which has the clever title: My Pedigree Has Collapsed! I figured that anything the Ashkenazi could do us WASPs could  do better. Nothing like a little ethnic rivalry. The other granddad of my three Dowell grandsons is Ashkenazi.

According to my RootsMagic software, my immigrant ancestor Richard CURRIER is my tenth great grandfather. But wait he is also my ninth great grandfather:


Yes, Nathaniel Currier of Currier and Ives fame was a 4th great-grandson of immigrant Richard. Thank you for asking. But back to my main point.

 If you insist in trying to read all the details, your browser may open a somewhat clearer image if you click on each page. All the individuals below the line of type projecting to the left halfway down each page are identical in each line. Only their generation number is different.



So one could theorize that I should have inherited some atDNA from these early Puritan ancestors since my pedigree collapsed under their weight. But that was a long time ago and many generations to pass the segments down. By now they would be well traveled, well worn and often recombined. Thank God for those thorough and well preserved New England vital records. As a result I know that my 10th great grandfather is also my 9th great grandfather is also my 9th great grandfather.

Saturday, March 5, 2016

SNP Tsunami Continues Into Third Year




Many of us spend a great deal of time, energy and money attempting to document that a particular ancestor of ours belonged to a particular tribe or ethnic group. We all get very excited when we find a family Bible or a diary of an ancestor that dates back two or three hundred years.

Don’t you wish your ancestors had carried a passport which got stamped at every branching point of their intercontinental migration route as they trudged through prehistory? Actually they did. In some cases our genomes have recorded more than a hundred thousand years of travel.

This travel is documented in the mitochondrial DNA of all of us. A separate and more detailed path is documented in the yDNA of men. Many call this anthropology. In Chapter 6 of my most recent book, NextGen Genealogy: The DNA Connection, I call this extreme genealogy. In either case it is the study of haplogroups – or the ancient clans to which our ancestors belonged.

Women ancestors were somewhat limited in what they could communicate to distant descendants because our mitochondrial DNA (mtDNA) contains only 16,569 locations in which they can record the presence of one of the four chemical bases that make up our DNA. Their paths through prehistory can be traced for our female lines using mtDNA test results. mtDNA was the basis for Bryan Sykes’ pioneering Seven Daughters of Eve.

Our men ancestors had tens of millions of additional locations where such information could be logged. What we look for today is where on our genomes these ySNPs occurred in this transcribed travel record. Once such a permanent change has occurred, it is passed down to all male descendants.

What are ySNPs and how do they differ from the ySTRs we have been testing since 2000?


Short Tandem Repeat (STR)
Pronounced "stir." This is a repeating pattern of genetic code letters at a location on the genome. The value is the number of times that pattern is repeated at that location.
Single Nucleotide Polymorphism (SNP)
Pronounced "snip." A single and permanent change in the DNA bases at a given location.

Consumer DNA testing to discover family history information began in 2000 with the focus on the Y chromosome (yDNA) which only males possess. Mitochondrial DNA testing for both genders soon followed but is somewhat limited because it has ONLY 16,569 locations to store a single bit of information. By 2010 autosomal DNA testing burst on to the scene and has become the most popular test.

By 2013 a new testing cycle for yDNA became available to genealogists. While the previous cycle had focused on testing ySTRs, the new wave examines ySNPs.

However, yDNA can record 3,500 times the data that mtDNA can. Therefore, it has the power to record a much more detailed migratory history.
Most of yDNA testing to date has been conducted on Short Tandem Repeats (ySTRs). When we talk about 12, 25, 37, 67 and 111 marker tests, we are referring to how many ySTRs were tested. STR testing is analogous to dispatching a census taker to a village which is known to have 12, 25… residences. In our scenario the locations of these residences have been defined by geneticists as being accessible and having a rate of mutation that is somewhat predictable. At each location our census taker records how many STRs are currently in residence.

In NextGen testing the focus shifts to Single Nucleotide Polymorphisms (SNPs). Instead of dispatching probes to specific, predefined locations, NextGen ySNP testing is more analogous to take satellite images along the entire Y-chromosome. Although the chromosome contains almost sixty million identifiable locations, current technology allows us to get reliable data from only about a fourth of those locations. Still this is an overwhelming amount of data. The computing power to analyze it has only recently become available.

At present ySNP chasing is only in its infancy. A vast majority of the SNPs we know today have been discovered in the last two years. The statistics in the chart below represent the number that had been placed on the International Society of Genetic Genealogists (ISOGG) yTree committee chaired by Alice Fairhurst:

Cumulative SNPs placed on the ISOGG yTree

Another way to look at this SNP tsunami is to view the new SNPs identified in a two year period (2013-2015) for R1b-L21, the most common male haplogroup in Western Europe today:

Known SNPs in R-L21 haplogroup in mid-2013 (Mike Walsh)

Known SNPs in R-L21 haplogroup in mid-2015 (Mike Walsh)

We are still working to find the exact location and sequence for many of them. In some ways our knowledge today would be like getting a SNP passport with several dozen “check point” stamps on it but in random order. We know that our genomes passed through all those points but are still trying to decipher in what sequence that journey occurred. The charts above for R1b-L21 represent ySNPs that we have been able to arrange in evolutional order. As more men are tested and we can document where they exited the main SNP trail, we can refine our chronology for all of us.

The chart below for sub-clade R-1026 is an expansion of the seven pale pink SNPs clustered at the bottom of the chart above. This subclade was unknown when the previous chart was drawn in 2013.


Courtesy of Alex Williamson -- www.ytree.net 

Even with this deluge there are many more thousands of SNPs to come. The NextGen curve is where the ySTR was in 2003 when 10,000 tests had been sold by FTDNA. Ironically, that is the number of BIG Y tests Bennett Greenspan reports FTDNA has sold to date. Full Genomes report their company has sold 1,500 NextGen tests. 

Most of the ySNPs that have been discovered have yet to be specifically placed and more will be discovered as testing numbers increase. The entire recently discovered R-S1026 haplogroup above is not yet integrated into the ISOGG ytree. It is only partially integrated into the FTDNA ytree. The R-S1026 chart contains many blocks or boxes that group newly discovered SNPs. At this point we believe we have the blocks in the correct chronological order of their appearance. However, we have yet to sort the SNPs within boxes into their correct order of appearance. And more remain to be discovered. Other haplogroups are in a similar state of discovery and growth. The SNP tsunami shows no sign of receding anytime soon. 


Saturday, February 20, 2016

Family Health History: TapGenes




When the possibility of DNA testing for identifying possible health issues is raised, a sizable segment of the medical community responds that such testing is unnecessary because a family health history is more useful. Fortunately, I believe the number of practitioners espousing this belief is diminishing. Actually, it’s not either/or. Genetic testing should be part of a comprehensive family health history.

Those of us who have been serious family historians for a while, recognize that we rarely have a complete health history of three or more generations of our family. Even if we have been able to collect death certificates for our parents, grandparents and great-grandparents (along with their siblings), really don’t have detailed information upon which medical diagnoses can be based. Some of our relatives died in wars, childbirth, epidemics or other causes before their underlying health conditions manifested themselves. In addition, many the causes of demise listed on many death certificates are too vague to add much guidance to present day diagnoses. Most patients, when asked to fill out family health histories in a clinician’s office, have far less reliable information than those of us who are genealogists.

DNA testing, even if is of whole genomes, also represents other challenges. Many medical practitioners are not knowledgeable about DNA and may feel threatened to admit this to their patients. This avenue to information within our bodies was not available when most of them received their professional training. Much as we might wish it were the case, DNA testing cannot provide information on all the causes of our current or future states of health. Environmental factors still contribute significantly.  The long running “nature” versus “nurture” debate rages on.

Part of RootsTech 2016, which I attended earlier this month, was an Innovator Showdown competition for a prize pot of $100,000. An international field of 46 competitors was narrowed to 12 prior to the conference. At the Media Dinner on Wednesday, that group was narrowed to 6 finalists. On Friday these remaining competitors were interviewed before thousands of attendees. The panel of judges then selected the winners with participation of the audience who voted on their smartphones. First place went to TapGenes. The winners received $20,000 in cash and additional in kind awards that more than doubled that amount.   


Yes, the eagle eyes of some readers have identified Judy Russell, The Legal Genealogist, seated in the lower left background, who was a member of the distinguished panel of judges.


TapGenes offers you the convenience of keeping all your family health history in one safe and secure place.
A visit to the TapGenes website will explain what this prizewinning app has to offer you and your family. If you wish to signup right away please use this link.

Wednesday, December 16, 2015

Promethease: For Your Health & Insomnia



On Sunday The Legal Genealogist, also known as Judy Russell, posted "All you want for Christmas..." is a DNA test kit. Her post began:
So… if that’s you this year, if what you really want for Christmas is a DNA test kit … which one do you get?
Her answer was very thorough and I will not try to duplicate it here. However, you would do well to read her thoughts. Her analysis of the options is sound, genealogically speaking, and she left very little to be added. Except....


Testing only for health related information:

All of us should know by now DNA testing is definitely not a case where "one size fits all." Judy knew this and she provided many viable options, but she left one out and I believe she did that on purpose. We will get back to what her purpose may have been later in this post.

In the last several days I have been approached three times by individuals asking what DNA test I would recommend for gaining health related information. Two wish to self test and the other is looking for holiday gift ideas for two sons. All of the would-be test takers are middle-aged. If they test they would become the kind of test takers all serious genetic genealogists love to hate. They all know little and claim no interest in knowing more about their ancestry except for how their genes may impact their own health. In addition they all claim not to be concerned about their carrier status for diseases that the FDA now permits 23andMe to report to clients. That really doesn't leave much from which to choose. 

Some information about prescription drug interactions with an individual's genome can purchased through a test offered by Healthspek which I have discussed in previous posts. However, that is only one part of the health related information inquiring minds would like to know about what is recorded within their personal genomes.

Several years ago I took a quick look at Promethease but found it to be not as user friendly as similar information presented by 23andMe. Since the reports generated by both companies were coming from the same source data, I opted to concentrate on those on my site at 23andMe


Hemochromatosis Carriers:

During the holiday season three years ago we offered to gift our children and their significant others with 23andMe test kits. One of the things we learned from this was that both one son and his wife were carriers for hemochromatosis -- which causes one's body to accumulate too much iron. The parents were not flagged as being at risk for developing this disorder but their offspring -- our young grandchildren -- were at elevated risk. I discussed this finding with my daughter-in-law who is a gynecological surgeon and medical school faculty member. I recommended that she relay this information to the boys' pediatrician so that he could make note of it in their files and monitor this possibility. My MD daughter-in-law asked if I would write a long email to the pediatrician that explained this development to him.

I did so but I found this to be ironic (pun intended) since I'm an information doctor not a medical professional. Some of you know that I have never had a biological science course of any description in my life. My insatiable curiosity about DNA was God's punishment of me when She read my transcript and realized my academic deficiency. So much for needing medical professionals to protect and guide us uninitiated civilians as we are introduced to the information in our own genomes. But I digress.


Promethease:

Back in September The Legal Genealogist wrote "A Healthy Choice" as a post to her popular blog. In it she presented a very thorough introduction to Promethease as a source for health related information from our genes.



Rather than trying to repeat her succinct prose my intent is to expand on the personal experiment she reported. Until recently I was unaware that self downloaded raw atDNA results from any of the big three testing companies can be uploaded and processed through Promethease. However, the 23andMe test chip has significantly more health related SNPs than the chips of the other two companies. FTDNA has made conscious decision to stay away to the extent possible from SNPs thought to be health related. This decision was made years ago in order to minimize the potential for regulatory problems with the FDA. As we learn more about our genomes, it is increasingly difficult to avoid SNPs with known health consequences. Ancestry discloses little about its rationale for selecting the SNPs on its chip.


Raw data from each of the major U.S. testing companies when processed through Promethease for three different users: 

23andMe Ancestry Family Finder
Legal Genealogist
Gray 17,613 11,225 10,070
Green 5,281 1,538 1,261
Red 413 255 166
Total 23,307 13,018 11,497
Dr. D
Gray 19,049 11,609 10,348
Green 5,580 1,572 1,296
Red 388 248 153
Total 25,017 13,429 11,797
Dr. D's wife
Gray 18,414 11,245 10,384
Green 5,519 1,491 1,265
Red 429 276 177
Total 24,362 13,012 11,826

Clearly customers get reports on about twice as many SNPs from 23andMe raw data than from the data from competitors. My little study has replicated Judy's. So if your only objective in taking an autosomal DNA test is to learn more about how your genetic component may contribute your future health, 23andMe raw data will give you more to analyze and analyze and analyze. That is what you will be doing if you go this route. Processing raw data from 23andMe or Ancestry only costs $5. Family Finder data costs $7 because xDNA must be downloaded separately and added to the mix to get the most complete picture that can be extracted from those data. If you have raw data from all three companies as does The Legal Genealogist and Dr. D., all your data can be loaded into Promethease at one time and processed for a total of $11.


Alzheimer's risk:

It is easy to drown in the data. In my own report Alzheimer's was associated with 156 SNPs: 56 good; 11 bad and 89 with small associations that have yet to be classified as either good or bad. You cannot look at the predictive power of a single SNP and be confident that you know something about how your genome may affect your future health. The human genome is far to complex for this kind of intellectual short cut.


SNPs currently thought to be related to Dr. D's Alzheimer's risk
If you have that obsessive-compulsive gene and love to pour over all the known data, this may be the test for you. If you have already done an atDNA test, for an additional investment of only $5 or $11 dollars, you can entertain yourself all night!


Holiday sale:

As most of you know 23andMe recently raised the price of its test kit to $199 for U.S. customers. If you are already a 23andMe customer, you recently should have received an offer to order kits for $149. This price is good for purchases completed through 11:59 pm PST on January 8, 2016. What you may not have noticed in the fine print is that you can place up to three separate orders. Each order can be for up to ten kits. This allows one to order as many as thirty kits at this sale price.


Caveat:  

If you are at all interested in using DNA testing to learn ancestry information for genealogical purposes, read Judy's December 6th blog post "Now... and not now" before you order any kit from 23andMe.


Tuesday, December 8, 2015

Ancestry to drop Family Tree Maker software. RootsMagic benefits?



The Ancestry blog announced today that the company would stop selling its desktop software program Family Tree Maker (FTM) as of the last day of this month. The company says it will continue to support current owners of Family Tree Maker at least through January 1, 2017. 


Our subscription business and website, on the other hand, continue to grow and we are doubling down our efforts to make that experience even better for our Ancestry community.

If the past is any guide to the present, it will be a waste of time for the genealogical community to try to influence Ancestry to reverse course on this matter. 

This behavior, while it may make business sense, does not enamor customers to trust Ancestry to be there for them in the long run. Ancestry has a history of buying or acquiring products and then abandoning them often with the loss of massive amounts of useful data lost in the process.

I was a user of FTM once upon a time. Then I moved to Family Origins. At the time I was thrilled because I thought this would mean Ancestry's marketing know how would increase the reach of Family Origins. WRONG. In retrospect it appears that Family Origins was acquired to get rid of competition for FTM. Family Origins was allowed to die a quiet death. Fortunately the programming team behind Family Origins came together soon after their non-competition clause of their sales contract expired and produced RootsMagic now in version 7.0.8.0.


RootsMagic along with Legacy on the Windows platform would seem to be among the companies best able to benefit from Ancestry's recent announcement. RootsMagic is already moving into the breach this evening with a special offer to FTM users.



Reunion is in a position to have a similar opportunity for those using FTM on the Mac platform. 


This decision by Ancestry should not lead to the destruction of useful genealogical data as the corporation's previous decisions to withdraw access to MyFamily.com sites did a couple of years ago. Access to yDNA and mtDNA test data conducted by Ancestry and by Sorenson Molecular Genealogy Foundation (SMGF) was also lost to the genealogical community and those who had contributed it when Ancestry decided to concentrate on autosomal DNA.

Taken by itself the decision announced today does not seem to be as damaging to the genealogy community as some of Ancestry's previous actions. However, it leaves this blogger wondering what if anything we should expect when Ancestry acquires former competitors such as Fold3, and Find A Grave? What should we expect from Ancestry's strategic alliances to make other databases available to its customer base?


Friday, December 4, 2015

Affordable Precision Medicine: The 23andMe Interlude


23andMe DNA Kit

In the first year of the Obama administration much attention was focused on affordable health care. Late that year 23andMe came to my attention when it sought out beta testers for its genealogy application the company was adding to its existing DNA tests for consumer health information. My wife and I quickly signed up and got what, in retrospect, became one of the greatest consumer bargains of all time. My primary motivation for testing was for family history information, but I soon became an advocate for enabling better health care by allowing citizens to "buy" reliable genetic information that might help them understand their current and future health prospects.

For the next 4 years consumers were able to acquire for a very reasonable price, information about:
  • their "differences in sensitivity or in the likelihood or severity of side effects" when taking 25 categories of drugs
  • their health risks -- either elevated, reduced or typical for 122 common disorders; 
  • the presence or absence of 53 "specific genetic variants that can cause certain health conditions" in the person tested; and 
  • the presence or absence of 53 "specific genetic variants that can cause certain health conditions" being "carried" down to offspring.

We generally didn't articulate these reports from 23andMe as having these 4 components. We thought of them as constituting the health report as opposed to the ancestry report that gave us information about our ethnic origins and offered us a chance to connect with unknown relatives who might help us fill in gaps in our family histories. It was only after the FDA took these reports from the marketplace in November 2013 and eventually allowed one of them to come back in 2015 that we began to realize how much we had lost. Note: 23andMe has recently marketed the original full health reports in other English speaking countries who are not protected by the US FDA.

The FDA never presented concrete evidence of actual harm done to consumers by the 23andMe health reports. The agency never alleged that the lab work was substandard or that the company did not really test what it claimed to test. All that the FDA took exception to was the interpretation of the results without the direct involvement of a health professional. The agency alleged that the average citizen might not be able to understand 23andMe's interpretation of the results. 23andMe was mandated to validate that its explanations could be understood on a case by case basis. 

I wish the FDA would apply the same standards to the drug adds  that inundate us every evening during the national news. We are one of 2 countries that allow this kind of promoting prescription drugs directly to public. The other country is New Zealand. These advertising costs contribute to the inflated cost of these drugs when they are prescribed. But I digress.

Within the last few weeks I have been asked to recommend DNA tests that could give information about the current and future health prospects for mature adults who were beyond child bearing age. Healthspek, a local startup about which I blogged a few weeks ago, offers testing for possible drug sensitivity or in the likelihood of or severity of side effects. However, this test costs as much or more than 23andMe. 

Randy Farr, CEO of Healthspek emailed me last week his comparison of the two:


23andMe
Healthspek
Price
23andMe raised their price in October to $199  (from $99).  It is likely they are still operating at a loss even with this increase.
Our website, un-channeled, states $499.  We have sold only one test so far at that price.  The website is not generally reached directly.  Our marketing efforts (through partners and direct) provide a link with this url: http://pgt.healthspek.com/discount.
Try it.  Then use the discount code CYBERMONDAY.  You’ll see a price of $299.  We have the ability to generate codes with varying discounts and private labeling.  This gives us the ability to build in (or not) a commission for channel partners.  $499 is a high enough ceiling that there is always a meaningful discount.
A similar company (www.getcolor.com) offers a genetic test specific to only breast cancer risk for $249.  Other examples exist.
Reporting
23andMe does not do PGT (pharmacogenetic testing). The biggest reason is probably this:  The value in PGT is NOT the underlying raw data,  it is in the translation of that data to decipherable and meaningful results in prescribing drugs).
Part of the cost of our test goes to the production of a patient-specific report that has several components (drug-by-drug metabolizing, gene-by-gene variants, general overview, etc.).
In 1st quarter next year this report will be expanded to include traditional (molecular) drug-drug interactions (this is not genetically driven).  While this is not genetic it is equally important in the task at hand-prescribing drugs more precisely.
So, our focus of our test – prescribing- goes beyond just raw data and even beyond genetics.
This is powerful stuff.
What’s included
Ancestry, carrier markers, some food and wellness.  It also has a social (blood relations) aspect that is cool.
1)      Complete report – drug-by-drug, gene-by-gene.
2)      Telephonic session with certified genetic counselor.
3)      Results deposited in free Lifetime wallet –Healthspek, best PHR on the market (per Apple and Appy Awards).
4)      Simultaneous delivery of results to consumer’s doctor.
General vs. Specialty
23andMe is a good generalist.  But it doesn’t, and can’t, give much help in specific areas that rely on robust research (‘what does this part of the genome mean?’).
Genetic Testing is currently available by many companies in the area of oncology, markers, carrier markers, pharmaco, specific diseases, diet, exercise, etc.
Companies that do specific genetic testing and results will always have a place in this market.  This is because knowledge and its display is what matters, not just the raw data.  23andMe can’t possibly be all things to all people.


This is still just one of the 4 areas previously covered by 23andMe reports. The FDA has cleared 23andMe to resume providing most of its "carrier status" reports. These tell one whether you are likely to transmit to your offspring conditions that are not manifested in you or your spouse. So between 23andMe and Healthspek, two of 23andMe original areas of health information are covered. That still doesn't provide feedback on genetic impact that may affect the health of an adult except for drug interactions--information provided by 23andMe prior to November, 2013.

The only way I know of for you to learn that kind of information is to take a 23andMe, Ancestry or Family Finder (FTDNA) test and subsequently process your raw data at a third part site. Remember, the FDA did not challenge the accuracy of the raw data generated and reported by 23andMe. 23andMe continues to provide this to customers. Online sites like Promethease offer data analysis reports of your raw DNA:
Promethease is a literature retrieval system that builds a personal DNA report based on connecting a file of DNA genotypes to the scientific findings cited in SNPedia
Biomedical researchers, healthcare practitioners and customers of DNA testing services (such as 23andMe, Ancestry.com, FamilyTreeDNA, etc.) use Promethease to retrieve information published about their DNA variations. Most reports cost $5 and are produced in under 10 minutes.

Breaking News

23andMe announced yesterday a temporary price reduction to $149. One quipster commented that he didn't know if this was a $50 price increase from 23andMe's recent price of $99 or a $50 reduction from the current $199 price. In any case if you are interested in buying a 23andMe kit in the US now is the time to act.

It is hard to predict how the current series of changes will affect the utility of the 23andMe product for serious genetic genealogists. Hopefully that will become clearer in coming weeks.

The more things change the more they stay the same. In late 2009 my wife and I bought 23andMe kits as beta testers for their new genealogy matching service for $149. That was half the regular price at the time. As most of you readers know the price has fluctuated over the last 6 years.

As much as many consumers want even cheaper prices, that may not be realistic if we want companies to be able to stay in business. Antonio Regalado reported in October in the Biomedicine News section of the MIT Technology Review:

we’ve seen several announcements by companies trying to lure consumers to learn about their genomes. Something they all have in common: they’re losing money doing it, at least for now.


As we approach the last year of the Obama administration, are we closer to affordable health care and precision medicine? I hope so.