Boston - "Who Do You Think You Are?" was the title of the opening keynote by Kenneth Chahine at the Consumer Genetics Conference. The answer gets trickier the more you learn. Chahine is the senior vice-president for DNA at the popular Ancestry.com genealogy company.
In May, AncestryDNA gene testing service was launched to provide customers with information about their genetic heritage. Currently the company has two million paying customers who have worked out 39 million family trees while accessing 10 billion different records. The ethnicity predictions from AncestryDNA can be associated with the family trees that its customers have put together to shed further light on their heritages.
So far some 50,000 customers have taken advantage of the service and there’s a long waiting list. Chahine noted that so far half of AncestryDNA’s customers are mixtures of three or more ethnicities. In addition, the company has identified 500,000 fourth cousin relationships among the users of its gene testing services. This number of fourth cousins is not too surprising considering that a reproduction rate of 2.5 per generation would yield about 1,000 fourth cousins after five generations. Basically, fourth cousins share about 0.4 percent of DNA from the ancestor that they have in common. At about 10 generations, for purposes of tracing relatedness, the genes shared by people become essentially indistinguishable from just the genes conserved in human beings.
Interestingly, AncestryDNA has found that lots of Americans are distantly related (have a most recent common ancestor) to one another back to colonial times. Why? There was a kind of genetic bottleneck largely because there were so few people living in what became the United States before 1790. The company estimates that between 1607 and 1790 about 900,000 people immigrated to this country. The largest share of immigrants were enslaved Africans, about 360,000 people. The next largest groups of immigrants came from England (230,000), Ulster (135,000), Germany 103,000), and Scotland (48,500). The result of this immigration pattern was that in 1790, nearly 2 million residents of the new United States were descended from English immigrants; 750,000 from Africans; 320,000 from Scotch-Irish; 280,000 from German; 200,000 from Irish; 160,000 from Scottish; and 120,000 from Welsh. But while many Americans assume their ethnic admixtures occured only in the new world (for example, an Italian grandfather marrying a Swedish grandmother), AncestryDNA's work on allele frequencies (differences in genes associated with different ethnicities), shows that a lot of ethnic mixing took place in Europe centuries before the ancestors of contemporary Americans arrived here.
Chahine offered a case study of one customer whose family came from Puglia in Italy. To his surprise, it turns out that his genetic test indicates a heritage that is 36 percent European Jewish; 17 percent Eastern European; 10 percent Southern European; 11 percent Scandinavian; 11 percent Middle Eastern; and 9 percent Turkish/Persian/Caucasian. Customers so far have not expressed any anxieties over such results, but instead are intrigued by them. The company is working to improve its tests to further probe ethnic differences among people of African and Asian heritage.
Watch Out for the Cops!
One participant asked what the company would do when it receives subpoenas asking for clients’ genetic information related to police investigations? Chahine responded that looking into a genetic database like AncestryDNA's for the purpose of a police investigation would be the equivalent of knocking on every door in Boston to a search for a criminal. He acknowledged that the day would come when police and prosecutors will try to search AncestryDNA’s database seeking to identify a suspect in a criminal case, but he insisted that the company would fight against such requests in court. So far as I know, there are no cases yet in which law enforcement officials have requested that a consumer genetics company turn over genetic data from a customer to them.
Who Wants Genetic Privacy Anyway?
Later, Chahine went into detail about the elaborate steps AncestryDNA takes to protect the genetic privacy of its customers. However, he noted with some bemusement that when many customers share their results willy-nilly with little apparent concern about privacy issues. I suggested that the fact that consumers of genetic testing do not appear to be all that worried about genetic privacy is a pretty good sign that company and regulator concerns over genetic privacy are exaggerated. I do concede that putting your genetic information in public (as I have) would make it easier for police to identify you in any investigation.
Who Do You Want Your Children to Be?
Another panelist, Good Start Genetics CEO Don Hardison, explained that his company is different from many other testing companies because his researchers look at an entire gene that is implicated in inherited diseases. Good Start offers pre-pregnancy carrier testing to physicians whose patients want to know the risks of passing genetic diseases to their children. Most people are carriers of one or more genes for particular recessive traits that they could pass on if they mate with another carrier. For example, cystic fibrosis is the most common lethal inherited disease in people of European heritage and about one in 20 people are carriers of a cystic fibrosis gene variant.
When Good Start scanned through the gene associated with cystic fibrosis they found 1900 variants, of which 550 could be implicated in causing the disease. So his company tests not for just the most common cystic fibrosis variants but all 550 of them. The result is that in a recent screening of 1,000 patients, their test found three of 32 disease-causing cystic fibrosis variants that would not have been revealed by standard tests. One of those variants would not have been uncovered by any previous test. Currently the company offers a panel that tests carrier status for 23 disorders recommended by the American Congress of Obstetricians and Gynecologists, the American College of Medical Genetics, and several national Jewish advocacy organizations. For what it’s worth, 23andMe, the testing company I used, tells me that I am not a carrier of the common variant associated with cystic fibrosis though I am a carrier for Alpha-1 antitrypsin deficiency.
Hardison noted that some 400,000 couples currently go to fertility clinics annually. Good Start’s pre-pregnancy tests give couples information that can help them decide to opt out of having children, use pre-implantation genetic diagnosis to select embryos that do not carry the disease gene, adopt, or go ahead and have children, armed with the knowledge of the disease risks. Interestingly, Good Start could test for many more disease risk variants, but has chosen not to do so right now because payers will not cover the costs of the tests.
A tragic but intriguing story of how next-generation whole genome sequencing is being used to diagnose infants with inherited genetic diseases was outlined by Neil Miller. Miller works in neonatal genomic medicine at Children’s Mercy Hospital in Kansas City. Researchers have identified more than 7,000 monogenic disorders — inherited diseases controlled by a single pair of genes. Miller explained that such disorders afflict 3 to 4 percent of children, and account for 25 percent of all infant deaths and 15 percent of pediatric hospital admissions. Thirty percent of the annual 66,000 neonatal intensive care unit (NICU) admissions are because of inherited diseases. NICU costs run from $3,000 to $8,000 per day. The somewhat good news is that there are early treatment options for 500 of the known inherited diseases. Genetic diagnoses can also rule out diseases, providing physicians with information that allows them to halt ineffective treatments.
Miller’s team recently used whole genome sequencing to diagnose extremely rare genetic diseases in six of seven infants. Sequencing to diagnosis took just 50 hours for each case. In one case, a five week old girl was suffering from constant seizures. Her whole genome was sequenced as were those of her parents. Miller’s team found nothing related to the known 174 genetic variants associated with epilepsy, but did find a novel mutation in the BRAT1 gene that resulted in the child’s malady. Miller concluded that whole genome sequencing was immediately useful and would soon be affordable for diagnosing diseases in neonates.