DNA Consultants Home of the DNA Fingerprint

Behind the Numbers:  Jim Bentley

Jim Bentley, DNA Frontiersman

(Part Three of a Series)

We interviewed  one of Chromosomal Labs Bode Technology’s senior staff members, Director of Sales and Marketing Jim Bentley, to get his perspective on industry changes over the past thirty-five-plus years.

Jim Bentley.

When did you first get interested in DNA?

JB: I’ll have to preface my answer with a few remarks on “the early days.” When I graduated from Arizona State University in the 1970s, DNA testing as we know it, was not really a field that was in existence. There was not a lot going on. The little work I did with chromosomes was using electron microscopy. I worked in the biochemistry department, however and performed hundreds of assays using poly-acrylamide gel electrophoresis, mainly for separation of proteins. This technique, although improved and streamlined remains in use today for DNA-STR separation. The field we’re in today where we can determine a person’s profile and compare it with others for forensics  for relationships, ancestry, missing persons, adoptions and the like, that technology hadn’t been developed yet. It wasn’t quite as easy as it is today.

Tell us more about the evolution of DNA testing.

JB: It basically began with blood groups and types. The first paternity test was done in a court case with Charlie Chaplin in the 1940s. He was excluded as the father, but the court said he could go ahead and pay child support anyway—probably, because he could afford it. Since that time, scientists started moving past groups and types into some other techniques. Human Leukocyte Testing (HLA), DQ-Alpha, and Restriction Enzyme STR testing (RFLP) are examples of the evolution of DNA testing.

The big breakthrough came when Dr. Alec Jeffreys at the University of Leicester discovered STR testing in England the late 1980s. He used STR profiling on the Colin Pitchfork case. Colin Pitchfork became the first criminal convicted on the basis of DNA evidence and as a result of a mass DNA screening operation. He was charged with raping and murdering two teenage girls. Since that time the forensic community has really refined the techniques to perform STR testing. They’ve made it simpler and more accurate. It’s really moved exponentially in the last twenty years. Today competent biologists and chemists can produce excellent results, every time.  Dr. Jeffreys has been knighted for his contributions.

So what got you involved?

JB:  I came out of college as a chemist, one interested in the medical field. I started out working in clinical chemistry and toxicology. The work we did with DNA was extremely limited and very costly. But I did stick with a career in clinical chemistry. Within four years after graduating from school I was managing a clinical laboratory in Houston, Texas called National Health Laboratories. It was a laboratory of about one hundred scientists and support staff. After mergers, acquisitions and such, that company remains as Lab Corp. (It performs more than 1 million tests on more than 370,000 specimens each day.)

What opportunities for professional growth did you have over the years?

JB: Through taking a lot of continuing education coursework, I became proficient and qualified as a general supervisor in clinical chemistry, toxicology, hematology, parasitology, microbiology, serology—everything except for tissue work like histology and cytology, which was done by certified medical experts in those specialties. My interests kept me in touch with the staff pathologists, however, as well as all the rest of the laboratory. Though my present-day field did not exist at the time I graduated, by staying current I was able to benefit from the changes and be part of an emerging valuable service provided not only to the medical community but also to the forensic one, and the general population at large.

What are some famous cases you’ve been involved with . . . that you can talk about?

JB:  Actually, that’s my problem. We’ve been involved in a number of high-profile cases, but we’re not allowed to talk about any of them. Most have been on the forensic side, serial killer trials in Arizona, also in California, some that made the news in Florida . . Texas . . .Georgia.

Were you involved in catching the Grim Sleeper?

JB:  Actually, that’s an ongoing case in Los Angeles we are familiar with, but we didn’t do the work on it, so we can talk about that one. The importance of the Grim Sleeper case has to do with familial testing and autosomal DNA. It was termed the Grim Sleeper case because there were a number of homicides that took place beginning in the mid-1980s, all with the same basic MO [modus operandi], and then the murderer went underground for fourteen years. The victims were typically prostitutes shot with a firearm. In 2010, a suspect, Lonnie David Franklin Jr., 57, was arrested and charged with multiple counts of murder. He has not yet been convicted, nor the evidence against him tested in court.

How was DNA used to catch him?

JB: So here were a number of cold cases, but they were being tracked, and the law enforcement authorities in Los Angeles continued to monitor progress. The sole survivor of one of the Grim Sleeper’s attacks furnished a description of him as a black man in his 30s, along with other details. According to her story in the press, he lured her into an orange Ford Pinto, shot her in the chest with a pistol, took Polaroid’s and raped her, leaving her for dead. In 2008, the body count was thirteen, and a $500,000 reward was put out for “America’s Most Wanted.”

It became the first use in California, and one of the first three cases in the United States, of the use of familial DNA searching, that is, using the FBI’s CODIS database to match one family member’s profile with a suspect’s profile. The LA police were able to provide a close partial match to  Franklin’s crime scene profile with that of his son, whose CODIS markers were on file for a minor crime. They then set up a kind of mini-sting operation at a pizza parlor in Buena Park, where they knew the family liked to eat. Undercover detectives masqueraded as waiters and busboys. When the family left, they whisked away an unfinished pizza slice. The crust yielded DNA which police linked on a more solid basis to Lonnie Franklin. It was the first high-profile case in which a family member’s DNA had been used to catch a criminal. The ACLU and others had been critical of familial searching on grounds of privacy, and there is still a lot of debate over familiar searching because it might open up the search and include those who hadn’t committed any crime.

Did this help produce new commercial products like the “cousin finders”?

Only a few states are doing familial searching, and they are pretty guarded about it. It’s hard for me to make a connection. Certainly, these developments have been concentrated in the past three or four years, but the use of this technique is spreading.

Are people legitimately suspicious about DNA databases?

JB: Fears surface from time to time. There have been claims that keep popping up that someone’s going to take everything that’s in the database and use it to determine genetic deficiencies that could lead to medical issues down the road. Once it was speculated that if such  information was released, insurance companies would begin denying people coverage based on their profiles.

This is the mother of conspiracy theories, isn’t it?

JB:  It really is. For the most part—not for everyone—the vast majority of the markers we are using are in the “junk DNA” area. That is, they don’t by themselves “do” anything or give you genetic information on the face of things. There may be one or two markers that possibly could be construed as yielding some medical information—such as a trisomy at vWA or TPOX [a CODIS locus]. But by and large, you are not going to be able to do any medical diagnostics with the markers we run. Usually trisomies such as Down’s syndrome would be physically expressed and not hidden. It’s a little different with SNP panels [single nucleotide polymorphisms] such as those run by 23&me. With a high number of those, it’s entirely possible to predict medical predisposition. That’s what they base their business on.

Let’s talk some more about the CODIS database.

JB:  It’s important to realize that even law enforcement doesn’t provide much access to the CODIS [Combined DNA Identification System] databank. That’s something I have to give the FBI credit for. They have developed a system that is secure. It’s the DNA administrator at each facility who has undergone FBI training and uploads the data under very strict rules, and they are notified of any “hits” that involve them, but otherwise there is very little access, and the use of the database is very even across the country. There are not a large number of portals that can be used to access the CODIS database. There are several hundred law enforcement laboratories that are running profiles across the country, and the database is best thought about on three different levels:  LDIS, SDIS and NDIS, local, state and national versions. Between our labs in Phoenix and Virginia, we’ve tested over a million profiles for entry into CODIS. That’s about one-tenth of the entire number. I can tell you there is tight security. Hundreds of thousands of investigations have been aided by a DNA hit (we don’t like to say “match” so much, because statistically nothing is 100%) generating a lead.

How did you get bitten by the genealogy bug?

JB: I’ve always been fascinated with ancestry. I think it came about because my father took an interest in discovering our family’s roots and had to do so at the time by traveling to Salt Lake City, Utah, and poring over whatever records he could find there about our fathers, and great-grandfathers, and great-great-grandfathers, and so forth. He had tintypes of some of the relatives. We had various pieces of the puzzle. My father pretty much consolidated everything back to William Bentley, who settled in Rhode Island in the early 1700s and had come from Bedfordshire, England. He put together a book for family use. He glorified a few of them and left a few out that weren’t ready for glorification. For the sensitivity of some of the relatives, he left a few details out, but it was a pretty solid piece of work. For me, it kind of fostered this interest in ancestry and its importance. Certainly, when I started at Chromosomal Labs • Bode Technology, we started looking at the various tools that could be used. Our history, to be sure, is passed down from generation to generation. Initially, we were using mitochondrial DNA, Y-SNP’s and Y-STRs and then autosomal STRs to determine how we’re connected to general and specific individuals back to the Revolutionary War days and how you are linked with the world population, what your roots were. I have a particular Y haplogroup of G2a, which is not one of the more common ones.

Hmm . . . you and Joseph Stalin.

JB:  [Laughs]. Is that what his haplogroup was? Uh-oh! He was one of the worst. Well, I got interested in G2a and hooked up with about 50 other Bentleys and we identified our founder  patriarch haplotype. I get emails from them on a regular basis. The other thing we tried to find out was what in the world were all these G2a’s doing in England. I don’t know. But one of the things I find in the literature most often was that the Sarmatians were horsemen that gave the Romans a pretty rough time. Eventually, they were decimated. The Romans took their remaining cavalry and pressed them into service for 12 to 13 years or longer. Some were dispatched to Hadrian’s Wall. Now do I know for a hundred percent certainty that’s where I came from? No, but its fun to regard that as a hypothetical personal history.

You have a Scythian gene, don’t you?

JB:  Yes, I do according to the analysis DNA Consultants did for my autosomal ancestry. The work Dr. Yates has done on the rare alleles supports a lot of the stuff the family has been putting together for years and years.  I was very pleased to get my Rare Genes from History report back showing I had the Scythian gene. That seems to go along with the Sarmatian theory about the Bentleys.

How do you see the industry changing over the next few years?

JB:  I can speak best about changes I am seeing in the field. They’re getting closer to having rapid DNA testing on a chip. This gives flexibility to those who want to use DNA as “point of use” testing. The FBI this past year came out at the Promega conference and said that within the next two years they would like to see wide adoption of “point of use” testing. The IntegenX prototype allows you to put your swab into a cartridge, insert it into the instrument on the fly and get your STR results in a few hours. Previously, Rapid DNA testing was not only time-consuming and lab-bound but it was very expensive. It cost several hundred dollars in reagents alone. As the technology improves to allow 2 hour testing in our lab or on a chip, reagent and personnel time continue to drop,  Now, the FBI would like to see point of use testing in every booking station in the country. At the last show, I also saw an instrument from Illumina that would run Y-STRs, mtDNA and autosomal DNA profiles simultaneously on one sample. Another change that is coming is we will see an expanded profile becoming the standard, perhaps something similar to the GlobalFiler kit from Life Technologies with its 24 loci. With the new technology you can increase the speed for amplifying the specimen by five times and achieve nine times the discriminating power or resolution.

Any final remarks?

JB: The DNA testing field is on the threshold of even greater accolades of appreciation both from the scientific community and the public. If DNA wasn’t even in anyone’s mind twenty years ago, soon it will be part of everyone’s daily lives.

 
























Sir Alec Jeffreys, inventor of DNA fingerprinting, and Jim Bentley at forensics meeting.

The question of ancestry has been of human concern in virtually all cultures and over all times of which we have any knowledge. Whether it be a story about the origin of a particular tribe or nation and its subsequent mixture with other groups, or curiosity about a family history, there is always the implication that we understand ourselves better if we know our ancestors and that we, within ourselves, reflect properties that have come to us by an unbroken line from past generations. As treasurer of the Marlboro Historical Society in Vermont, I am the recipient of requests for printed copies of the Reverend Ephraim Newton’s mid-eighteenth-century history of our town, 70 percent of whose pages consist of “Genealogical and Biographical Notes” and a “Catalog of Literary Men.” Over and over our correspondents write of the “pride” they have in descending from these early settlers.

Surely pride or shame are appropriate sentiments for actions for which we ourselves are in some way responsible. Why, then, do we feel pride (or shame) for the actions of others over whom we can have had no influence? Do we, in this way, achieve a false modesty or relieve ourselves of the burdens of our own behavior? As a descendant of late-nineteenth-century Eastern European immigrants I cannot depend on Reverend Newton’s pages to explain my frequent contributions to The New York Review, but neither have the extensive “begats” in Genesis 10 or Matthew 1 been more enlightening.  Read More...

PRESS RELEASE
Rare Genes from History:  DNA Consultants’ Next-Generation Ancestry Markers

PHOENIX -- (Oct. 1, 2012) -- DNA typing has gone from successes in the criminal justice system and paternity testing to new heights in mapping genetic diseases and tracing human history. John Butler in the conclusion to his textbook Fundamentals of Forensic DNA Typing raised an important question about these trends. How might genetic genealogy information intersect with forensic DNA testing in the future?

"At DNA Consultants, that new chapter in DNA testing arrived several years ago," said Donald Yates, chief research officer and founder. "As we approach our tenth anniversary, examining human population diversity continues to be the whole thrust of our research, and it just gets more and more exciting."

The company's DNA database atDNA 4.0 captures and puts to use every single published academic study on forensic STR markers, the standard CoDIS markers used in DNA profiles for paternity and personal identification. In 2009, the company introduced the first broad-scale ethnicity markers and created the DNA Fingerprint Plus.

But its innovations didn’t stop there. In October 2012, the company announced the launch of its Rare Genes from History Panel.

Why CoDIS Markers?

“Theoretically,” noted Butler in 2009, “all of the alleles (variations) that exist today for a particular STR locus have resulted from only a few ‘founder’ individuals by slowly changing over tens of thousands of years.”

How true! Hospital studies have determined that the most stable loci (marker addresses on your chromosomes) have values that mutate at a rate of only 0.01%. That means the chance of the value at that location changing from parent to progeny is once every 10,000 generations.

So the autosomal clock of human history ticks at an even slower quantum rate than mitochondrial DNA. Like “mitochondrial Eve,” its patterns were set down in Africa over 100,000 years ago when anatomically modern humans first appeared on the stage of time.

Though the face value of the cards in the deck of human diversity never changed—and all alleles can be traced back to an African origin—as humans left Africa and eventually spread throughout the world, alleles were shuffled and reshuffled. Humanity went through bottlenecks and expansions that emphasized certain alleles over others. Genetic pooling, drift and selection of mates produced regional and country-specific contours much like a geographic map. 

By the twentieth century, when scientists began to assemble the first genetic snapshots of people, it was found that nearly all populations were mixed, some more than others. The geneticist Luigi-Luca Cavalli-Sforza at Stanford University proved that there is almost always more diversity within a population than between populations.

So if there is no such thing as a “pure” population—a control or standard—how are we to make sense of any single individual’s ancestral lines? Statistical analysis provides the answer. And rare genes are easier to trace in the genetic record than common ones. Their distinctive signature stands out.

Back Story:  It All Began with the Melungeons

About the same time as DNA Consultants' scientists were cracking the mystery of the Melungeons, a tri-racial isolate in the Appalachians, they became aware of certain very rare alleles carried by this unusual population in relatively large doses. The Starnes family, for instance, in Harriman, Tennessee, was observed to have a certain rare score repeated on one location in the profiles of members through three generations. The staff dubbed it “the Starnes gene.”

Soon, company research had characterized 26 rare autosomal ancestry markers—tiny, distinctive threads of inheritance that reflected an origin in Africa and expansion and travels through world history. Genes in this new generation of discoveries were named after some distinctive feature associated with the pattern they created in human genetic history--for instance, the Kilimanjaro Gene after its source in Central East Africa. The Thuya, Akhenaten and King Tut genes were named for the royal family of Egypt whose mummies were investigated by Zahi Hawass’ team in 2010.

The Starnes Gene” became the Helen Gene. Because of its apparent center in Troy in ancient Asia Minor and predilection for settling in island populations, it was named for "the face that launched a thousand ships," in the famous phrase by Christopher Marlowe.  

All 26 of DNA Consultants' new markers are rare. Not everyone is going to have one. But that’s what makes them interesting, according to Dr. Yates.

Coming from all sections of human diversity—African, Indian, Asian and Native American—they are like tiny gold filaments in a huge, outspread multi-colored tapestry, explains Phyllis Starnes, assistant principal investigator and wife of the namesake of the first discovery. But does that mean that her husband has a connection to Helen of Troy? The markers don’t work on such a literal level, but it does imply that Billy Starnes shares a part of his ancestral heritage with an ancient Greek/Turkish population prominent on the page of history.

Over the past two decades, geneticists have worked out the macro-history and chronology of human migrations in amazing detail and agreement. The Rare Genes from History Panel is another reminder--in the words of an American Indian ceremonial greeting--that “We Are All Related.”

These rare but robust signals of deep history can act as powerful ancestral probes into the tangled past of the human race as well as unique touchstones for the surprising stories of individuals.

For more information about the science of autosomal DNA ancestry testing, visit DNA Consultants or check out its Twitter or Facebook page. 

Environmental doctor Anne Marie Fine of Scottsdale, Ariz. was one of the first physicians to adopt genetic tests as part of her practice in 2002. Recently, she gave a brief introduction to the role epigenetics plays in human diversity at the 12th annual Conference on Diversity in Vancouver, British Columbia. Her paper with Donald N. Yates, "Epigenetics and the Autosomal DNA of Human Populations: Clinical Perspectives and Personal Genome Tests," should appear soon, but in the meantime you can watch a short video of her epigenetics presentation (5:37). Epigenetics is beginning to loom as a much more important factor in multigenerational health than mere genetics. We would be interested in your comments!

Every year in the United States about half a million paternity cases are performed proving or disproving whether an alleged father is the true parent of a child. Sometimes there is a court order to do this; at other times, it is sheerly for personal information. The determination of parentage is made based on a simple comparison of a small rock-hard number of genetic markers in the DNA fingerprint of the child and alleged father. Samples are extracted from a 30-second cheek swab and processed at any of an estimated 2,000 forensic labs across the country. The standard in place since about 1997 has been a set of 30-32 biallelic or double values each person carries on loci spread across their chromosomes, making for a virtually unique identification signature that reflects the equal DNA input of mother and father (and in fact all grandparents and all ancestors).

Often termed CODIS markers (standing for Combined DNA Identification System), these alleles or variations are the magic numbers underlying the popularity of paternity tests as well as the national passion for jailing or exonerating crime suspects. If a value is found in the DNA profile of the child and is not present in the two observed values of the alleged father on the same locus, this constitutes what is known in the paternity business as an exclusion:  the alleged father is almost certainly not the true father. Conversely, if all the alleged father’s values can be detected in the child’s on each location, one after another, that male is judged to be the child’s biological father to a 99.999% certainty. Paternity tests are simple math.

A famous paternity test involved proving who was the true father of the baby born to Anna Nicole Smith in 2006. After her death in early 2007, several men came forward claiming to be in father, including a European prince, Anna Nicole’s bodyguard and a convict who had been a former boyfriend. Larry Birkhead pressed his case. When the results came in, he was declared by Bahamian court to be the baby’s biological father. The child’s original birth certificate was amended to show this.

Can paternity testing be used in a reverse process to establish the identity of a father, given only the child’s DNA profile? No, but with enough DNA profiles available for comparison the missing member of a family group can be reconstructed by comparing alleles they must share, called obligate.  Doing so is a matter of logic and statistics, mostly just either-or, deductive logic.

I became interested in reconstructing a parent’s profile after many of DNA Consultants’ customers inquired if such a calculation or estimate was even possible. Some were adopted persons who had no recourse to testing their parents, some knew one parent but not the other, and some had no access to parents. They were either uninterested or unavailable. In a special category were females who were only-children with both parents deceased who wanted to know something about their father, but who could not take a Y-chromosome haplotyping test, as they did not carry a copy of their father’s male DNA. In this respect, autosomal DNA testing is the great equalizer.

My father, Lawden Henry Yates, died in 1978. My mother, Bessie Cooper Yates, lived to the advent of DNA tests, but I failed to obtain any sample from her before her death in 2006. I had siblings and half-siblings still living, however, so in 2010, I constructed a family group autosomal DNA study with the help of Crystal Wagner at Chromosomal Laboratories/Bode Technology. The results were very satisfying. This paper and blog post will serve as a report to those who are interested.

Step One
I was fortunate to have the participation of three half-sisters by my father, along with his second wife, their mother. Comparing mother and daughters I was able to verify the obligate alleles each daughter must have received from the mother.

Autosomal alleles are fixed in our genealogy, have little or no mutations (unlike YSTRs, which mutate from generation to generation, as do mitochondrial nucleotide positions, though more gradually over time)[*] and derive from both parents equally by recombination at the moment of conception. They are copied and preserved without change in every cell of our bodies. The mother is responsible for half of the equation.  By a process of elimination the other number on each row of the lab report must represent the father’s contributions.  This method is completely logical and unequivocal. There can be no other answer to the problem. No studies suggest these pieces of our double helix DNA change significantly in transmission from one generation to the next or mutate over time in genealogies. Their values and patterns are strictly attributable to heredity.

Step Two
The father’s alleles are confirmed by a comparison with three children by his first wife, my mother.  

Step Three
By the same watertight process we can now proceed to the mother’s reconstructed DNA profile. In it, we can expect to visualize the final piece of the puzzle, proceeding from the known to the unknown according to the immutable laws of autosomal DNA and genetic inheritance.

We have arrived at my mother Bessie Yates’ DNA profile by a multi-step process of extrapolating it using three of her children and three children by her husband’s second marriage, along with the test results of my half-sisters’ mother. Seven tested profiles yielded two reconstructed ones. In the process we have also recovered my deceased father’s DNA profile.

Separating Mother and Father’s Contributions to Ancestry
Having overcome these hurtles, I was most interested in the utility of the results. I felt confidant about the method. But what excited me most was to see how my own autosomal ancestry results might be respectively apportioned in my parents. For this, I ran a DNA Fingerprint Plus on them both. The findings were very satisfying to me personally, helping solve many questions I had always had about what ancestry I got from my father, what from my mother and what from both.

Let’s start with American Indian admixture. My own DNA Fingerprint Test, as well as percentage tests through another company, suggested a relatively large amount, perhaps one-quarter all told by various measures, but family tradition had placed Native American heritage solely on my mother’s side. To be sure, my mother gave me a Native American mitochondrial haplotype, indicating a female line going back to a Cherokee woman in Georgia, traced as far back in records as 1790. Extensive genealogy research showed, however, that my father’s great-grandmother was also a Cherokee with the surname Thomas from North Carolina. What did the new autosomal DNA profiles say?

On a rough measure, I have received a “double dose” of Native American II, a marker co-relating with 80% of 24 tested American Indian populations in the atDNA 4.0 database. (Two siblings and one half-sibling received only single doses.) This seemed to indicate that I had some degree Native American (not possible to say how much) from both parents. True enough apparently, judging from the top world matches for my mother and father. I give here the top ten for comparison.

These results confirmed that my father did have some Native American, although evidently not as much. They also suggested that although both bore about the same mixture of European and Native American ancestry (including high matches to Melungeon), my mother had a more pronounced Native American cast, her highest match being to North Asian, one of the supposed Asiatic feeder populations of Native Americans, whereas my father’s top match was European American. Based on profile frequencies, my father was five times more likely to be European American than American Indian if subjected to forensic profiling, whereas my mother was 18 times more likely to come out as a Siberian Native than Northern European. Sometimes, it seems, exotic ancestry rises to the top. My overall conclusion was that my mother probably had 3/8 and my father 1/8 Native American heritage, which corresponds to their proved genealogies.

In my own profile, combining those of my parents, here are my megapopulation results:

Self (Donald N. Yates)

According to these frequencies, my mother and father’s Native American ancestry reinforced each other in me to make my top four matches Native American (or Siberian-Mongol-Turkic), so that I am about twice as likely to be graded into the Native American category by population statistics than the European. Similar conclusions emerged from my siblings’ tests, and a diminished presence of Native American indicators was confirmed in my half-siblings, although their mother seemed to evince some Native American as well as my father, the shared parent. All participants in this study had grandparents born in North Alabama.

Further observations are possible. For instance, I was surprised to see a large indication of Jewish ancestry in my father’s profile. Genealogy confirms as much, as the family surname is Hebrew (an anagram of Ger Tzedek similar to Katz, Kohen Tzedek). The emigrant Yates figure was reportedly an English Jew in seventeenth-century Virginia. My mother also showed Jewish ancestry. Both parents matched Melungeons, an Appalachian ethnic type suspected to have Sephardic Jewish forebears. My father’s family included uncles named Josephus, Manaen, Irbin, Azariah, Lazarus and Sherith—apparently his Middle Eastern matches were truthful to a partial Muslim background. My mother’s mother was named Palestine, and the names Isaac and Jacob were ubiquitous in her family tree. But neither side of the family claimed any Jewish heritage. It was left to autosomal DNA to reveal that hidden inheritance.

Although never performed before to my knowledge, this method of reconstructing autosomal profiles can be useful to others seeking to recover unavailable relatives’ genetic fingerprints and to separate parents’ contributions to their children’s ethnic and ancestral stories. Since it is based on immutable markers in DNA it rests on more solid ground than Y chromosome alleles or mitochondrial mutations. The challenge in exploiting the method is to have enough subjects in your family group study. In my case, I was fortunate to have a prolific father with six living children. I would like to conclude by thanking all my siblings, half-sisters and my father’s widow. Their participation made it possible to present a true first in DNA genealogy.

Read the working paper
A Method of Reconstructing Parentage and Ancestry by Autosomal DNA Profiles

Go to Learn about DNA

The sequencing of the human genome capped off the 20th century's tireless search for genetic causes for all diseases.  But epigenetics is the hot new science now. Dr. Anne Marie Fine, a Scottsdale physician, certainly thinks so. Dr. Fine spoke in Paris recently on Epigenetics and Beauty and next month will present a paper called "Dining at the Epigenetic Cafe" in Monte Carlo, Monaco at the largest European physicians' anti-aging conference.  In June she will present a paper entitled "Epigenetics and the Autosomal DNA of Human Populations: Clinical Perspectives and Personal Genome Tests at the University of British Colombia, Canada," with Donald Yates, principal investigator at DNA Consultants, along with participating in a 90 minute colloquium on epigenetics, autosomal DNA and ethnic identity.  Clearly, epigenetics is stealing the show!

From the Fine Center for Natural Medicine News, here is how Dr. Fine describes epigenetics and its promise:

"Epi" literally means "above" so epigenetics are the influences from above that affect the DNA. Epigenetics refers to modifications to DNA and chromatin, the protein scaffolding that surrounds the DNA, that persist from one cell division to the next, despite a lack of change in the underlying DNA sequence.  So the "epigenome" refers to the interface between the environment and the genome.  This is the basis behind the new science of epigenetics- how the environment affects the cellular DNA. Cells are bathed continuously in a sea of changing environmental conditions.  This means the epigenome is dynamic and responsive to environmental signals especially during development, but also throughout life.  It is becoming increasingly apparent that stress, environmental chemicals, and nutrient deficiencies are some of the biggest factors that promote epigenetic changes to the DNA.  In addition, some of these changes in gene expression persist long after the exposure has stopped.  What this means is that these changes can transcend generations.

It is becoming clear that a wide variety of common illnesses, behaviors, and other health conditions may have at least a partial epigenetic etiology, including cancer, respiratory, cardiovascular, reproductive, and autoimmune diseases, neurological disorders such as Parkinson's, Alzheimer's, and other cognitive dysfunctions, psychiatric illnesses, obesity and diabetes, infertility and sexual dysfunction.  Effectors of epigenetic changes include many agents, such as heavy metals, pesticides, tobacco smoke, polycyclic aromatic hydrocarbons, hormones, radioactivity, viruses, bacteria, basic nutrients, and the social environment, including maternal care.  It has even been suggested that our thoughts and emotions can induce epigenetic changes.

"Incredibly, only about 2 percent of diseases can be attributed to locked-in single gene mutations," says Dr. Fine.  Most disease occurs as a complex interaction between genetic susceptibility and the environment.  This means, while there are genetic predispositions,  there are environmental triggers that actually start the disease, but also environmental factors that protect against developing the disease.   The key is to understand which factors promote disease, and avoid them, and which protect, and seek them out.  Our genetic makeup doesn't necessarily determine our biological fate.  "Genes may load the gun, but environment pulls the trigger," says Dr. Fine.

James Watson once said that the double helix contains a library of detailed information about all generations of our ancestry "if only we could read it." Combining epigenetics and the advances in autosomal DNA tests, we are beginning to read the whole of human medical, evolutionary and ethnic history, at least in outline form. 

At a time when it seemed that American science had bitten off more than it could chew with the Human Genome Project, Craig Venter and his innovative company published "A New Strategy for Genome Sequencing." Appearing in the journal Nature in 1996, the Venter multi-center approach bypassed laborious gene mapping and allowed the HGP to meet its goal of full sequence information on the human genome in 2000.

"In the race to sequence the human genome," write the editors of Nature's DNA Technologies Milestones, "research groups had to choose between the random whole genome shotgun sequencing approach or the more ordered map-based sequencing approach." The choice of randomness versus order was present from 1982, but the Venter strategy was resisted for many years. Finally, in 1996 it was accepted and given an equal emphasis with the more orthodox approach.

After a standoff between the two groups of scientists, "a showdown ensued, with the biotechnology firm Celera Genomics wielding whole-genome shotgun sequencing and the International Human Genome Sequencing Consortium wielding map-based sequencing. Yet when the dust settled, it was a draw -- both groups published their initial drafts of the human genome concurrently in 2001."

The maverick technology helped make high throughput genomic sequencing at commercial labs an economy reality and gave birth to a range of new DNA tests within the reach of ordinary consumers like you and me. Today, fifteen years later, those interested in autosomal ancestry testing and personal genomics have biologist and entrepreneur Craig Venter and his irascible persistence as a scientific pioneer to thank.

In a paper to be delivered at the American Marketing Association's meeting in Washington in June, Elizabeth C. Hirschman estimates that the number of people who have purchased a DNA test now exceeds 1.5 million. Her work suggests that the value of the market (excluding paternity testing) in 2011 will reach nearly $150 million in sales. That seems like too big an industry to escape government oversight, and it's true that several scientists have targeted the direct-to-the-consumer DNA testing business for criticism, particularly personal genomics companies like 23andme.

Before another academic grant gets written to send out another industry questionnaire, however, marketing professionals and public policy analysts ought to have a look at Hirschman's new case study, destined, we think, to become a classic. "Altruistic Economics and Consumer Cooperatives in the DNA Marketspace" sketches a vibrant picture of DNA test takers busy following up on their results in social networking sites like DNA Communities and even joining in the design process for product improvements by the leaders in the industry. No unhappy campers there!

The proof of the pudding is in the eating. Rather than mount yet another policy making roundtable, would-be regulators should just order some of the DNA tests available from today's leading companies and judge for themselves how accurate or valuable or harmful they are. That makes a lot more sense than writing another food review for a restaurant they do not intend to patronize, or for a cuisine that is not to their taste.

The AMA's Marketing and Public Policy Conference is the premier national and international event for marketing academics, public policy makers, and marketing practitioners interested in social and public policy.

Another point made by the paper is that "The industry has completed the introduction, early growth stages and consolidation phase of its life cycle . . . . It is a mature field facing few new technology thresholds, and it is still very much confined to the United States, Canada and England." That having been said, it may be too late to regulate the industry. It seems to be doing fine all by itself. Like the pharmaceutical and computer industries, the DNA marketspace is an American phenomenon we should all just basically let thrive and be proud of.

Altruistic Economics and Consumer Cooperatives in the DNA Marketspace

 

Discussion is accelerating in the United States and European Union to regulate private genomic testing that provides consumers medical information, according to Science magazine and the European Journal of Human Genetics. No mention is made in the reams of white papers about ancestry testing, but some of the pitfalls and bureaucratic morasses in the thinking about true genetic/medical testing are fairly ominous, if not silly.

"Although there has been speculation about the potential psychosocial harms of testing [that is, genomic medical testing], such as an increase in anxiety or encouragement of fatalistic behavior, there are, to date, few studies addressing these concerns," writes the reporters for Policy Forum in the Oct. 8 issue of Science. "The limited evidence tends to be reassuring, even for risk information associated with relatively serious ailments...however, the scope for potential harm from unnecessary or unproven treatment after genetic risk assessment is an important unstudied question" (pp. 181f.).

We commend scientists and physicians for finding a new field of study divorced from reality but have to wonder what they will do about ancestry testing once they have conquered and tamed Frankenstein's elder monster. We suggest the following guidelines:

• Labeling on Internet sites and Zen Shopping Carts that explicitly states, "The claims for this ancestry product have not been evaluated by the U.S. Government Accountability Office (GAO), U.S. Federal Trade Commission (FTC), House Energy and Commerce Committee, Food and Drug Administration, National Institutes for Health or Department of Bioethics and Humanities, University of Washington School of Medicine, Seattle, WA 98195 USA."
• Predictive ancestry information may be hazardous to your progeny.
• No animal has been harmed in the production or clinical evaluation of this ancestry test.
• If you discover you have ancestry you did not expect, take a deep breath. Then take a healthy dose of skepticism, followed by two aspirins and a glass of water.

To Do DNA or Not to Do DNA?

Much Ado about Nothing

American education is in such a state of decline and confusion that the following new program, with all its pros and cons, seems tantamount to a mad hatter's tea party. We reproduce a description of it from Nature in all its carefully nuanced and agonizing detail. We suggest that rather than fretting over whether DNA testing companies might use predatory marketing on teenagers or students be pressured into making purchases and be psychologically damaged by DNA results, the school authorities worry about real threats like the fast food poisons served up in the cafeteria franchises on their campuses. Or overpriced and watered down textbooks. Or alcohol in dorms. Or date rape. Or just about anything else.

A DNA education

Nature 465: 845-46 16 June 2010

Taking personal genetic testing into the classroom brings ethical and legal sensitivities to the fore. Although personalized genetic testing is still very new and controversial, its increasing use in health care seems inevitable — a trend that makes it essential to give consumers and physicians a better education in the technology's strengths and weaknesses.

That was the rationale behind an announcement made last month by the College of Letters and Science at the University of California, Berkeley. This year, instead of sending its incoming students a book for later discussion in class, the college will send them a kit to swab their DNA. If they so choose, students can send in their sample to be analysed for three common gene variants that indicate how an individual metabolizes alcohol, lactose (found in dairy products) and folic acid, a vitamin common in leafy green vegetables.The impulse behind Berkeley's announcement was commendable.

But officials there were too hasty in designing the programme, as evidenced by the firestorm of criticism it triggered and the changes the university has instituted in response. For example, each student's kit will now include not just details of the measures being taken to safeguard and anonymize the data and descriptions of the genes to be tested, as originally planned, but also information about the ethical and legal issues surrounding genetic testing. In addition, the university has modified a contest that accompanies the programme: the prize will no longer be a full genetic test conducted by a commercial testing company, which could be perceived as an endorsement of such firms, but will instead be cash.

Finally, organizers have decided to hold off revealing the tests' results until just before a lecture at which the benefits and limits of genetic testing, as well as the three chosen genes, will be discussed in detail. They will also give an accompanying lecture on the ethical and social dimensions of genetic testing. And students will be able to seek private counselling about their results if they wish.

Although it was wise of Berkeley to make these improvements, concerns remain. The university contends, for example, that there will be no pressure on students to participate in the genetic testing. Not only will they be told it is entirely optional, but students — or in the case of those under 18 years of age, their parents — will sign an informed consent document. Moreover, faculty members will never learn which students participated and which did not. But critics still worry about indirect pressure: the very fact that the kits are being sent to all of the college's incoming students could give them the impression that their participation is expected, in which case their choice may not feel so free.

A telling contrast in approach has been provided by Stanford University in Palo Alto, California, which announced a similar course designed for medical students shortly after Berkeley announced its programme. Recognizing the potential for controversy from the outset, Stanford officials first appointed a task force of basic scientists, clinicians, legal professionals, genetic counsellors, ethicists and students who spent a year designing precautions against coercion and conflicts of interest by the institution, and working out access to counselling.

The result is a well-thought-out programme — which also includes a research component designed to test a commonly held belief: do students truly learn better when the information presented to them is of personal relevance?

That said, the Berkeley and Stanford programmes are both still experimental. No one has all the answers to the issues they raise, which is why designing such curricula will involve constant refinement and evolution. It is shortsighted for critics to oppose such endeavours on the grounds that experts don't yet know how to interpret genetic information or how to integrate it into medical care. That is changing rapidly — and these two programmes are only the beginning of a long conversation that needs to happen on campuses worldwide.