You’ve probably heard of “paternity testing” and “prenatal screening,” but how many people understand the terms “genotype” and “genomics”? While many people aren’t familiar with genetic terminology, chances are that at some point during your life you’ll find yourself discussing information that has been obtained from analyzing your genome.
Genomics is the study of genomes, the full set of hereditary information (or genes) present in an organism. As a field, genomics has grown exponentially over the past several decades. The bacteria Haemophilus influenzae was the first to be sequenced in 1995; however genomics became really exciting with the completion of the Human Genome Project, which set out to sequence the human genome using DNA taken from four anonymous donors.
Genomics is more than just genome sequencing. It also focuses on analyzing genetic data to determine how gene products function and interact, and which gene products are expressed in a given set of conditions. The Human Genome Project aimed to locate and identify the 20,000 to 25,000 nucleotide stretches of DNA in the genome. Initiated in 1990, the project published the complete human genome sequence in 2003.
The published sequence reflects the general arrangement of genes found in every human being. At the same time, it does not completely reflect the genomic sequence of individuals, because every organism (that is not a twin or clone) is genetically unique.
Enter the era of personal genomics. Personal genomics is all about determining and analyzing DNA sequences for individuals. This relatively new field is growing rapidly and has already found a number of applications, particularly in the area of genetic testing. Genetic testing refers to the process of examining and interpreting an individual’s DNA using bioinformatics tools. Police use genetic testing to identify suspects and victims at crime scenes as well as biological relationships in paternity tests. Doctors also perform genetic tests on newborns to screen for various genetically based disorders that can be treated before the disease progresses. In addition, some individuals screen themselves to determine whether there is a chance that their children will have a particular genetic disorder. Pre-natal diagnostics test whether a fetus has a genetic disorder, while other types of genetic testing can be performed to confirm a diagnosis of a disease, to identify individuals at risk for developing a particular disease or disorder, and how an individual may respond to certain chemicals or drugs.
How does analyzing a genetic sequence provide information about disease susceptibility? Although humans share the same genes, individuals can possess different variations of each gene, called alleles. Variations in the sequence of a gene may lead to differences in the appearance and/or behaviour of a gene product. In the case of certain genes, possessing a particular variant has been found to correlate with an increased risk of developing a specific disease. Various genes have been linked to breast cancer, Burkitt’s lymphoma, leukemia, a hereditary form of retinoblastoma, as well as many other conditions. These linkages are determined by genome-wide association studies which look at large numbers of people with or without a particular disease. Researchers then analyze the DNA sequences to determine if those with the disease share common genetic features.
Genetic testing used to be mediated by professionals such as doctors and genetic counsellors. However, over the past few years a number of companies have sprung up that offer this service to anyone who can afford it. These direct-to-consumer (DTC) companies argue that every individual has the right to access their genetic information. All a person has to do is send in a DNA sample and pay up. The company then analyzes the sequence to provide information about the customer’s likelihood of developing certain diseases later in life. In addition, some companies make predictions about an individual’s reactions to certain drugs and offer other services. For example, one DTC company called 23andme helps customers “fill in” their family tree by comparing their genotype with those of other customers and assigning biological relationships based on genetic similarity. The company also claims it can map a client’s origins by determining which ethnicities his or her ancestors likely belonged to.
Those intrigued by these possibilities should keep in mind that costs range between $500 and $999, depending on the company and the information you want to obtain. But is it even worth it?
An article recently published in Nature suggests that predictions obtained from DTC companies should be taken with a grain of salt. The article compared the results obtained by two different DTC companies (Navigenics and 23andme) after testing five individuals for their susceptibility to 13 diseases. The study found that while the companies’ predictions matched perfectly for four of the diseases, the remaining seven diseases involved predictions with 50 per cent agreement or less between the two companies. Although the sample size in this example is small, it shows that there are flaws with DTC testing. The article points out that the genotypes determined by each company matched more than 99.7 per cent of the time, indicating that the raw data was quite accurate. In addition, DTC companies base their predictions on results obtained from scientific studies. The fact that predictions given by different companies do not always agree is not necessarily a sign of incompetence.
U of T researcher Dr. Stephen Scherer points out, “As with everything there are variances […] most of the data the DTC companies deliver is based on relative risks with lots of mathematics behind them. The data is mainly ‘grey’ and not black and white, but that is no different than most other medical data.”
The authors of the Nature article suggest that the differences in predictions reported by the two companies may partly lie in the fact that each test uses different disease markers. Diseases with a genetic basis are caused by a combination of genetic factors, and each company chooses the disease markers that it feels provide the best predictions. Part of the reason for the disparity in predictions likely arises from the information each company uses to establish its analyses. Hence, the problem likely lies in an imperfect understanding of the connection between genetic factors and disease.
Scherer suggests that the accuracy of DTC testing could be improved by taking into account other kinds of genetic variations. Currently, DTC companies only look at single-nucleotide variations called single-nucleotide polymorphisms (SNPs) in DNA sequences. However, there are many other kinds of genetic variations: nucleotide additions, deletions, sequence inversions, and duplications called structural variations. These are very common and can also increase an individual’s susceptibility to developing a particular disease. “The importance of structural variation to gene expression, protein structure, and chromosome stability is being increasingly recognized in normal development and disease,” says Scherer, who argues that structural variations are “gain[ing] more prominence in genomic medicine.”
Of course, the best way to obtain genetic data is to sequence the entire genome. For the most part, only genes thought to be linked to certain diseases are analyzed to determine disease susceptibility. This means that the sequences of all variants need to be known. Sequencing reveals all the variations present throughout the genome.
Since the Human Genome Project, DNA sequencing technology has improved significantly and the costs have also fallen dramatically. The complete sequence published at the end of the project in 2003 cost $2.3 billion, while the first individual’s genome sequence, published several years later, cost several million. In November 2009, Complete Genomics claimed to have sequenced a full genome for $1,700. The DTC company Knome offers full genome sequencing for $68,500. Promises abound to drive down the cost to $1,000 or less within the next few years. Some believe that in the near future it will be affordable to sequence the genome of every individual in the United States. Having such a wealth of information will undoubtedly be invaluable to researchers, but does having access to one’s genetic information have any impact on the individual?
Experts point out that predictive genetic testing is only valuable if it leads to behavioural change. For example, if an individual discovers that he has a higher risk of developing colon cancer, this might motivate him to get screened for it earlier. However, it is unlikely that an individual with a two per cent higher risk of obesity will significantly change his or her eating and exercise habits. And what about diseases like Huntington’s? A positive genetic test for this disease means that an individual will definitely have it later in life. Not everyone may want to know about their predispositions to certain illnesses.
This issue only scratches the surface of the huge number of ethical, practical, and legal issues that have arisen with the growth of personal genomics. Privacy is a primary concern when it comes to genomic information. Another common concern is that genetic data indicating a susceptibility to certain illnesses may lead to genetic discrimination by insurance companies. The Genetic Information Nondiscrimination Act, passed in 2008 by U.S. Congress, protects individuals from such discrimination by health insurance companies and employers, but not life insurance companies.
Then there is the issue of DTC companies and what laws will regulate them from exploiting naive and uneducated consumers. Several European countries have resorted to banning DTC testing companies outright. There have been cases where DTC companies have been accused of making claims unsupported by scientific evidence. Commentaries on this issue express the need for greater transparency in the companies’ methods, increased consumer education, and government agencies to play some role in regulating their actions.
In addition, questions are being raised about the way genetic information is used in genomic research. In some studies, genetic samples are gathered from children with consent from their parents or guardians. Some argue that by the time these children reach the age of majority, they may decide that they do not want their genetic information to continue being used and should therefore be contacted and asked for further permission. Others argue that it is unrealistic to track down and contact every person whose DNA has been sampled.
In other cases, research may require linking genomic information with medical records. Harvard lecturer Patrick Taylor claims that seeking consent when it comes to using personal information for research will result in biased samples that pose a huge barrier to carrying out effective research. Nevertheless, in either debate, there is general agreement about the need to protect privacy, whether or not consent is given.
These heated debates hint that current regulations used for controlling the use and accessibility of genomic information are inadequate and will have to be rethought as the personal, economic, and political ramifications of personal genomics become more evident.
The Human Genome Project provides a glimpse into a possible future in which people are at ease with accessing and sharing their genomic data, where genetic testing and full genome sequencing is easily accessible and allows individuals to play a more prominent role in making decisions regarding lifestyle and health. This may also be a future for which we are not prepared, where genetic data is exploited and used by employers to discriminate between potential employees, or by DTC companies who make unreasonable promises to uneducated consumers.
Whether we are prepared for it or not, personal genomics seems to be the way of the future, and that future is coming fast.
