In the years following FDA approval of direct-to-consumer, genetic-health-risk/DTCGHR testing, millions of people in the US have sent their DNA to companies to receive personal genome health risk information without physician or other learned medical professional involvement. In Personal Genome Medicine, Michael J. Malinowski examines the ethical, legal, and social implications of this development. Drawing from the past and present of medicine in the US, Malinowski applies law, policy, public and private sector practices, and governing norms to analyze the commercial personal genome sequencing and testing sectors and to assess their impact on the future of US medicine. Written in relatable and accessible language, the book also proposes regulatory reforms for government and medical professionals that will enable technological advancements while maintaining personal and public health standards.

When individuals sign on to a DNA ancestry test, they understand that the company will undertake an analysis of certain segments of their genome, called ancestry information markers (AIMs). These segments can, under proper analysis, reveal their genetic descent from certain regions of the world.

Over a period of 20 years, family genetic genealogy, through the purchase of consumer ancestry testing kits, has been one of the fastest growing family activities of this generation. Citing data from the International Society of Genetic Genealogy, the Washington Post reported in 2017 that eight million people worldwide were involved with recreational genomics. It is estimated that by 2019 about 25 million people had signed up for a DNA ancestry test offered by one of the dozens of companies that have entered this marketplace. The kits are sent to a person’s home with return packaging that includes a reservoir for depositing saliva or swabs for sampling cheek cells. The MIT Technology Review predicted that by 2021 there would be 100 million consumers of ancestry DNA services.

Most human genetic diversity is found within populations rather than between populations. Scientists have reported that any two individuals within a particular population are as different genetically as any two people selected from any two populations in the world. Given this finding, how can science use a small percentage of genetic diversity between populations as markers of ancestral origins?

Much of recreational DNA ancestry offers consumers a long reach into the history of their descent by discovering which biogeographical population most closely matches their DNA profiles. The science and DNA analytics provide probability estimates that their DNA markers (ancestry informative markers, or AIMs) are most likely from a particular continent or even a specific country. But DNA ancestry tests have applications that go well beyond recreational genealogy. Even prior to the growth of this sector of direct-to-consumer testing, DNA was used to determine paternity and to establish identity in criminal investigations. An important and largely unintended application of ancestry DNA testing has been the uncovering of family secrets: “Why does my father look so different from his parents?” or “Why are my mother’s skin tones so much darker than those of her parents?”

As we noted previously, the science behind DNA ancestry requires that one compares the unique genetic markers on the consumer’s DNA sample with the frequency of those markers in reference panels representing different regions of the world. When the field of DNA ancestry began, it was a scientific project that involved the search for biogeographical DNA. Scientists could use changes in the human genome to determine how ancient populations moved around the globe. The further populations moved across the globe and the more time elapsed (many thousands of years), the greater the number of mutations or genetic variants. Genetic ancestry began with a half-dozen distinct continental regions and with markers called hypervariable microsatellites, or short tandem repeats (STRs) of DNA, 2–6 base pairs in length. These microsatellites were considered ideal at the time because they had a high heterozygosity, which means two different alleles at a site. A site that has an AA is homozygous, whereas one that has AG is heterozygous. The more diverse the alleles, the greater the chance of distinguishing allele frequencies among populations. Initially, scientists used changes in the maternally inherited mitochondrial DNA (mtDNA) and the paternally inherited Y chromosome. That changed when autosomal markers were chosen for ancestry analysis.

In order to locate people’s ancestry to a region of the world through their DNA, the markers on their DNA sample have to be compared to population reference panels for the regions that form part of the comparison group. These ancestry inference methods have served medical research, forensic science, and commercial popular genealogical interests. According to Santo et al., the reliability of any ancestry inference depends on the existence of reliable population reference databases. Many researchers and ancestry DNA companies utilize different sources for population data on different countries. For example, ALFRED is an allele frequency database supported by the Yale Center for Medical Informatics, which has genomic data from population samples across the globe. You can enter the name of a country or population group, such as Siberian Yupik (the sample was collected from unrelated Siberian Yupiks from northeastern Siberia, Russia) and it will provide information on the number of people (29) and/or chromosomes sampled (58).

The criminal justice system began using DNA to solve crimes in the 1980s, after a geneticist from the University of Leicester in the UK developed a method for sequencing certain segments of chromosomal DNA. Those segments, called short tandem repeats (STRs), were expressed differently in different people, in contrast to the 99.9 percent of our DNA that is the same, and thus could be used to establish an indicator of personal identity (see Chapter 1).

As a recreational activity, with no serious consequences at stake, it barely matters whether the results consumers receive from their DNA ancestry tests accurately represent the percentages of their ancestry from different geographical regions. Given that there are no international standards for such testing, unlike genetic disease tests, it is not surprising that the results from different ancestry testing companies vary. As noted in Chapter 4, there are several stages in the analysis of a person’s saliva or cheek swabs where the criteria, reference frames, or analytics can vary among companies, yielding different outcomes.

When you purchase a DNA ancestry service you are sent a kit containing instructions for submitting a DNA sample. Most companies provide a plastic tube, which they ask the test-taker to fill with saliva or cheek swabs, seal, and return. When the company receives your DNA test sample it is processed for analysis. As noted previously, the vast amount of your genome does not distinguish you from other individuals. Therefore, your genome is broken down into segments of DNA that contain the alleles of interest, rather than it being fully sequenced. Here is how AncestryDNA describes the processing of the DNA samples it receives from customers:

By this point in the book, we have explored multiple perspectives of DNA ancestry testing, beginning with its commercial success as a consumer recreational activity, its serious scientific foundations in population genetics, its applications in criminal investigations, and its social and ethical consequences in searching for one’s identity.

If human populations in different geographical regions can be identified by DNA, while the vast amount of human DNA is identical, then, in the regions or places on the genome that are variable, there must be markers that reveal biogeographical regions of origin. DNA polymorphisms (letter changes in the nucleotides) are currently the choice markers because most human polymorphisms are characterized by alleles that are unevenly distributed among the world’s distinct populations.

Stories of family deceits and deceptions have become commonplace in a media receptive to personal tales of triumph and tragedy. A distinguished geneticist learns in his mature years that his mother, while married to his legal father, had a secret affair that begat him. A best-selling author discovers that her paternal DNA was from a medical student serving as a sperm donor and not her legal father, who traced her ancestry deep into Eastern Europe. A woman who, as a newborn, was left in a bag abandoned in the foyer of a Brooklyn apartment building searches for her biological parents 23 years later. These revelations are the result of the millennial DNA ancestry revolution.

The purpose of DNA ancestry genealogy is to determine what the geographical origins are of an individual’s ancestry, regardless of where he or she is currently living. The scientific premise behind this exercise is that people’s DNA contains sequences of their ancestors’ DNA, which can be traced back hundreds or even thousands of years, and that their ancestors were settled in a region of the world that remained relatively isolated. This isolation allowed ancient populations to remain inbred within certain geographical parameters. Inbreeding is the mating of humans closely related by ancestry. It is more likely to occur in isolated, non-migrating populations, resulting in a loss of genetic diversity and a high incidence of birth defects. Mutations in the DNA circulating within these inbred populations can provide a genetic fingerprint of the geographical region in which they were located.