Limitations of DNA testing

When DNA testing companies like, for example, 23andme began to offer direct-to-consumer genetic tests, interest in testing one’s DNA became increasingly popular. Su and colleagues [40] revealed in their study about the motivation of buying a genetic test that there are five principal reasons why individuals decide to test their DNA, and that is, health, curiosity and fascination, genealogy, contributing to research, and recreation.

The rise of new advanced technology in geneticshas not only extended the possibilities to test one’s individual genome, but also brought forward scientific research opportunities, andfurthermore, induced novel approaches with respect to biological application. Next-Generation Sequencing (NGS) has changed considerably biological research by means of reducing reaction volume, and furthermore, increasingsimultaneously the number of sequencing reactions [41]. Especially the costs might have played a key role why Next-Generation Sequencing became popular in the scientific community and why genetic ancestry testing companies emerged on the market and started to offer direct-to-consumer genetic tests. According to The National Human Genome Research Institute,the cost per Megabase (a million bases) of DNA sequence and the cost per genome in September of 2001 came to $5.292 and $95.263.072, respectively. In contrast, the cost per Megabase of DNA sequence reached only $0.045 and the cost per genome $4.008 in January 2014. Especially the change from “first generation” sequencing platforms, that is, Sanger sequencing with capillary-based instruments (October 2007: $397 cost per Megabase of DNA sequence, $7.147.571 cost per genome) to “next generation” sequencing platforms (January 2008: $102 cost per Megabase of DNA sequence, $3.063.820 cost per genome) led to a decrease in costs [42].

The decreasing costs and the concurrent possibility of massively parallel sequencing not only led arise DNA testing companies, but also opened up new research areas like, for example, “metagenomics”, which allows to investigate the microbal and viral content of the human body [43], or Genome-Wide Association Studies (GWAS) which is applied to detect genes that are

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associated with diseases in order to evaluate risk like it was done, e.g., for coronary artery diseases [37]. The new technology in genomics became alsoincreasingly important in forensic sciences, that is, in human identification, as larger multiplexes might exhibit similar or even greater power to discriminate genetically individuals [44].

Some genetic testing companies offer their customers information about their risk for diseases. Incorporating new technology in research areas like personal genomics or medical research, however, poses new challenges that have to be resolved first. One of its challenges is to bioinformatically process, and subsequently, interpret the great amount of data obtained by the new instruments [45]. Furthermore, most Next Generation Sequencing technology in medical research so far was applied to investigate gene variations in populations of European descent meaning that a genetic association of a gene with a disease in the European population might not exist in a population of Africa [46]. Moreover, someone might not develop a disease despite carrying a risk gene for the respective disease. Thus, the validity of one’s predisposition to a disease by now should be treated with caution as research on this topic is still in its infancy. It is therefore especially necessary that consumers of genetic ancestry tests receive comprehensive information about their results [47] although research on gene-associated diseases indeed might prove to provide reliable information in the future about one’s predisposition for a disease. At least, an increased positive attitudefrom 2002 to 2010 regarding genetic tests was found in a population in the Netherlands when considering the future benefits and use of DNA test [48].

An important component of Genome-wide association studies is the previous estimation of genetic ancestry. However, autosomal markers sometimes have not the power to distinguish genetically populations from different geographic regions. That is, depending on the population under study a set of autosomal markers might be more or less useful in distinguishing genetically populations. For example, a set of 128 autosomal markers (Ancestry Informative Single-Nucleotide Polymorphisms) was able to distinguish ancestry in African and Mexican Americas [49], but was less useful in determining admixture in populations of Eurasia [50] meaning that the outcome of a genetic analysis depends both on the population under study and the genetic markers that were selected. Consumers of genetic ancestry tests should be especially cautious when the company is providing ancestral links to famous historical characters like Cleopatra, Napoleon, or the Queen of Sheba. It might be possible that there are indeed ancestral links, but usually they are so general, and thus, on the personal level meaningless. The reason behind this is the rapid accumulation of ancestors. An

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individual has theoretically after 200 generations 2200 _(~1.6*1060_{) genetic ancestors. However, in} practice there never had existed a population that size 200 generations ago. After 20 generations the same individual would have theoretically 220 _{(~1,000,000) ancestors, but in reality, again someone} would not have this number of ancestors as not all genealogical ancestors contribute genetically to one’s genome [51]. Ralph and Coop [51] have shown in their study that many of the ancestors within Europe are the same and shared among people meaning that even individuals from geographically distant populations within the continentshare the same set of ancestors that lived about 1,000 years ago whereas individuals living in neighboring populations even share 2-12 genetic ancestors over the last 1,500 years.This means, that going back far enough many people can exhibit ancestral links to a famous historical person.

Uniparental markers are powerful tools to trace back one’s geographic paternal and maternal origin because of the lack of recombination, high mutation rate, and the small effective population size which make the markers geographically more distinctive [33]. However, mitochondrial DNA gives information only about the maternal and the Y chromosome only about the paternal ancestor.Furthermore, haplogroups of mtDNA and Y chromosomes are rarely unique to one population, and thus, often provide information only about broad geographic origin [52]. For example, Ely and colleagues [53] found in their study that <10% of African Americans could be traced back to one single geographic region in Africa. Thus, the authors concluded that only few people will be able to trace their maternal ancestor to a particular region or ethnic group in Africa. It is also possible that only a small fraction of African mtDNA haplotypes have been detected so far which might explain why 40% of African Americans do not match with African mtDNAs [53]. Another aspect that has to be taken into consideration is that ethnic groups that existed 200 or 400 years ago might differ from ethnic groups that nowadays exist. Therefore, conclusions about one’s ethnic originin Africa have to be treated with caution when only the mtDNA or the Y chromosome was analyzed.

The most comprehensive approach in investigating one’s ancestors is the combination of all three genetic system markers, because, for example, autosomal DNA might reveal a principal European ancestry, but the same individual might still exhibit an African Y and/or mtDNA haplotype [33]. Especially in individuals of recently admixed populations like in the Americas due to the Transatlantic Salve Trade, the combination of different genetic markers can reveal unexpected patterns of admixture as males and females from different continental populations contributed unequally to the gene pool in the Americas.

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Tracing one’s genetic ancestry back to a geographical region underlies continuous improvements. For example, a new method, called Geographic Population Structure (GPS) was able to place 83% individuals from different parts of the world to their country of origin, and even a quarter of about 200 Sardinians to their village [54]. Moreover, researchers also began to develop methods that allow for determining the time of admixture from a specific geographic area [55]. For example, in the context of the Transatlantic Slave Trade, Moreno-Estrada and colleagues [39] found two migration pulses from two geographic different regions in Africa into the Caribbean.

However, since the study of genetic variation among human populations, discussions about ‘racial’ categorizations in human genetics became the center of many interdisciplinary scientific disputes. For example, scholars from various research fields ranging from the humanities, social sciences, life science, medicine, and law engaged in an intensely interdisciplinary dialogue at the Stanford University to work out which race and ethnicity categories can be used in human genetics [56]. In order to evade ‘racial’ categorizationsby the scientists themselves, many life science researchers have classified their study populations according to “self reported ethnicity” like it was done in a genetic study in Colombian populations [57], but also in Hispanics and African Americans of the U.S. [58].

Concerns about DNA testing especially appear, because information about one’s ancestry components might lead to a change in one’s notion of identity. As all people, from the genetics point of view, are admixed, Baylis [59] has illustratedelaborately that identity is not found in the genes, but in the society that constructs racial identity. DNA does not imply racial identity, but concerns about DNA testing are still explicable as categorizations in human genetics might be misunderstood, misinterpreted and misused as it can potentially provoke people to act like racists. Therefore, dialogue across disciplines in academia is necessary to find a common agreement how to categorize human populations in the life science, also because controversies about how to label groups of individuals still remain [56]. However, dialogue within academia is probably not enough, and thus, has to be extended to the people outside academia where it should be explained not in jargon, but in plain language to avoid racism.

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3.4 Investigating the TAST with genetics