When the Human Genome Project wrapped up in 2003, it revolutionized human genetics research.
By RIMSIE MCCONIGA
When the Human Genome Project wrapped up in 2003, it revolutionized human genetics research. The 10-year project determined the sequence of DNA present in a human. This recipe for life, DNA, will be the subject of a presentation as part of Park University's fourth annual Johnson Family Lecture Series in Science on Tuesday, March 19, which will feature Dr. Bryant McAllister speaking on direct-to-consumer DNA tests.
“I will focus the presentation at Park University around the surprising, or potentially unsettling, aspects of findings from a DNA test,” says Dr. McAllister. “Many customers have the reaction, ‘that can’t be accurate.’ Thus, I’ll focus on the different surprising outcomes to highlight aspects of the test results that are the most robust and are more speculative.”
Dr. McAllister says that because the human genome contains 3 billion bases in its DNA, determining the sequence of a human genome was a challenging and time-consuming endeavor. However, the result has been the explosion of genome biology, where the genome sequence of many organisms has now been determined and used as the basis for most biological research. Our understanding of differences in DNA sequence among individuals has expanded dramatically. These DNA differences influence the physical and behavioral diversity among humans, including health conditions.
The project has resulted in a phase of exponential growth in “recreation genetics.” The marketplace for DNA tests for individuals continues to soar. The number of AncestryDNA customers doubled in each of the past several years. AncestryDNA has more than 10 million customers in its database, and if the growth trend stays on the same trajectory as the past several years, they should exceed 20 million customers this year. Its customers are mostly U.S. based. 23andMe has more than 5 million customers in their DNA database. The MyHeritage company, based in Israel, is also growing rapidly and has a global customer base.
Dr. McAllister says one big difference exists between scientific studies that aim to generalize findings from a sample of data and commercial DNA tests. These companies aim to make specific interpretations for your individual and unique genetic profile.
“You can learn about yourself from the interpretations of your DNA,” says Dr. McAllister. “Personally, I find the list of people I’m related to in the database as the most helpful feature of these tests, because I use these matches with cousins based on our DNA as a tool for family history research. When I know I’m matched with someone in the database because we share a recent common ancestor, I want to know the identity of the common ancestor(s).”
Most people who take the DNA tests are motivated because of curiosity about their ancestors and where they came from, which Dr. McAllister says isn’t an accurate representation of what the test does.
“However, in doing this, a person may discover new relatives that they had not previously known about, such as an adoptee,” says Dr. McAllister. “They may also discover that the oral family history does not match the true biological history. For example, I found a match on Ancestry that was a previously unknown grandchild of my grandfather. My grandfather was a bit wild, so most of my family has found it amusing. The match, however, seems less amused about this new revelation about his grandmother. The participants in this affair have all passed, but it’s interesting how modern tools are uncovering the stories that went to the grave with them.”
Even with the family surprises that come with testing Dr. McAllister says he is an avid AncestryDNA user. “The AncestryDNA tests of my parents, their siblings, and cousins form part of the tools I use for genealogical research. I’ve also done specialized DNA testing on other platforms for genealogical research. The DNA test results include a list of relatives with an estimated relationship to the tester. From these relatives, I can organize from the list sets of individuals that share a common ancestor or a common ancestral couple. This ancestor(s) may be someone I already have historical information about from documentation, or it may be someone that is discovered from the DNA matches. In these two cases, the DNA matches are either supporting the historical record or providing clues that can be used to inform the search for historical records.”
Most people have a general idea of where their ancestors were from and have been told a personal history from parents, grandparents, aunts and uncles. Dr. McAllister says there are however, some surprise findings in that the ancestry composition estimate doesn’t agree with what the customer knows about their personal history.
“Most cases are not a surprise, but rather a mismatch between expectations of the test,” says Dr. McAllister. “Americans tend to think of themselves as 50 percent German, 25 percent Irish, and 25 percent English, or some variant on this theme of breaking down their ancestors to countries of origin. They are then surprised when the results report the person is 45 percent English, 15 percent Irish and Scottish, 15 percent German, 15 percent Scandinavian, and 10 percent Broad Northern European. The lack of fit between the family history and ancestry composition prediction represents a discrepancy between what the person thinks the test will tell them and what the test is actually attempting to predict. These tests are predicting the geographical regions where the customer shows the greatest genetic similarity with peoples having deep roots in that region. This similarity can be due to having ancestors from that geographic region, but it can also be due to where your ancestors came from to settle in that region, or regions where your ancestors' cousins migrated to.”
But hand-in-hand with the fascinating and educational results of these tests comes some disturbing and frightening privacy issues that accompany the explosive growth of this industry.
While there are stories almost every day about adoptees finding birth parents through these tests, or donor-conceived individuals finding the identity of an anonymous sperm donor. Dr. McAllister says anonymity can no longer be guaranteed for biological relationships. “We are approaching a point where essentially anyone can be identified through a DNA test of a close relative. Law enforcement have realized this feature and are using recreational genetic databases for criminal investigation. There are lots of third-party websites that will accept DNA data that a customer downloads from AncestryDNA, for example, and then uploads to the site. GEDmatch is one of these third-party sites used by lots of genealogists. Law enforcement is using GEDmatch, uploading DNA profiles from a crime scene, to identify the relatives of the perpetrator of the crime. By identifying the relatives of the perpetrator, this may lead to the identification and arrest of a suspect. It did in the case of the Golden State Killer, and several other cold cases.”
Family Tree DNA, sells DNA testing services to the FBI and also allows the FBI access to their database. 23andMe and AncestryDNA expressly forbid use of their databases for these purposes, but Dr. McAllister says they are not entirely immune to nefarious access that does meet their usage agreement.
Dr. McAllister’s academic research interest focuses on genome organization in the context of chromosome structure. Chromosomes represent the different DNA molecules present in a genome, and he wants to understand how the rearrangement of the DNA facilitates evolutionary processes such as adaptation.
He studies flies for this work and he says the basic principles of genetics work the same between humans and flies. Most of what we currently understand about human genetics originates from work on flies and other model organisms.
In contrast, he says, humans probably represent the best characterized organism at the level of DNA sequence data.
While genetics is a rapidly moving field, Dr. McAllister says most of the discoveries fit neatly into our current understanding.
For many people who don’t know their family’s health history some of the companies provide interpretations of health risks for the customer, which are based on well understood genetic variants that are known to increase risk for a medical condition, such as Late-Onset Alzheimers. “Finding that you do have an increased risk of Alzheimers may be unsettling to a person, because there is no treatment,” says Dr. McAllister. “For customers that want to know this information, they often view the knowledge as powerful, even though it’s not actionable. Customers should keep in mind, however, that the Alzheimers interpretation is limited. 23andMe is basing their interpretation on one major risk variant; however, there are many variants known to increase the risk of developing Alzheimers. A customer may have a family history of Alzheimers, do a 23andMe test, and find they are not at increased risk. The genetic variants responsible for Alzheimers in this person's family may not be the one 23andMe tests, so they may not have gained any information about the Alzheimers risk in their family.”
Dr. McAllister says that because genetics is the common thread throughout all of biology, the applications of genetics are also endless. Genetic applications touch on many aspects of modern life, whether it’s commercial DNA testing, agriculture, or medicine.
Most of all Dr. McAllister likes that genetics provides a window into the continuity of life. And he says it provides a perspective on the past and also can be used to predict the future.
The presentation will begin at 7 p.m. in the Jenkin and Barbara David Theater within Alumni Hall on the University of Parkville Campus. Admission to the lecture is free, but registration is requested at park.edu/johnson.