This introductory seminar course and the materials presented here focus on the science underlying personal genome analysis, comparison of tests available from the varied companies that dominate the direct-to-consumer genetic marketplace (e.g., Ancestry DNA, Family Tree DNA, The Genographic Project, and 23andMe), and building the knowledge to navigate the results obtained from the analysis of your own DNA sample. Materials are organized to support this course, aimed at introducing someone with only a basic understanding of biology to The Personal Genome and the discoveries that lie within, but are available to anyone. The site is actively "under construction".
COURSE OBJECTIVES: In this course you will:
Contrast different types of genetic information indicative of ancestral relationships
Recognize the existence of genetic structure among human populations across the globe
Build proficiency in the conceptual foundation for the methods that underlie tests of human ancestry
Navigate the 23andMe web platform to view the various interpretations of genome data
Investigate the relationship between genotype and phenotypic characteristics with known genetic basis
Evaluate the personal and the potential societal impacts from commercialization of genetic tests
Develop skills for contributing to a productive group discussion about science and humanity
Consider the possible outcomes of DNA testing
Evaluate the value of the results versus potential foreseen and unforeseen consequences
Identify the potential impacts of DNA testing on you and your relatives
Relate the molecular structure of DNA to genome sequence
Recognize the presence of a shared genome among cells of your body
Prepare authorization forms and samples for DNA testing
Integrate parent-offspring relationships into the broader Tree of Life
Apply a ‘tree thinking’ framework to individuals, populations and species
Recognize the utility of shared features, such as SNPs, as indicators of common ancestry
Trace the uni-parental history of the mitochondrial genome and Y chromosome
Contrast between unique mutations and common SNPs in ancestry analysis
Recognize the geographic patterns and the prevalence of haplogroups
Identify your placement within the Y chromosome and/or mtDNA tree of humanity
Interpret the different predictions of the ancestry composition
Recognize the presence of ancient genetic variants revealed by Neanderthal ancestry
Reading: assigned on ICON
Evaluate the importance of reference populations in ancestry analysis
Contrast geographic patterns of shared and private variation in humans
Relate patterns of genetic variation in modern human populations to global colonization
Contrast different patterns of inheritance; mtDNA, Y, X, and autosomes
Consider the role of recombination in shuffling autosomes and X chromosomes
Calculate degrees of relatedness and expected similarity in autosomal DNA
Evaluate the relationships revealed with other users indicated by shared genome segments
Recognize the value of testing known relatives to partition branches of your family tree
Predict the percent similarity expected based on degree of family relationship
Genetic Variation and Phenotypic Diversity
Recognize the influence of the genotype on the appearance of a phenotype
Contrast between traits with simple versus complex genetic causation
Evaluate the association between genetic variants and complex phenotypes
Navigating Your Genome
Compare regions of your genome shared with relatives
Use SNPedia to identify variants of interest and explore your genotype
Test Results and Health Risk
Interpret the meaning of increased health risks associated with genetic variants
Recognize the impact of genetic variants on the effectiveness of pharmaceuticals
FDA Regulation of DTC Genetic Tests
Evaluate potential outcomes of learning about disease risks
Recognize the current level of impression in risk assessment from genetic data
Downloading and Using Your Genome Data
Download your DNA test results and identify fields of the text file
Identify tools available for further analysis and interpretation of genome data
Direct-to-Consumer Genetic Tests; Which Test To Do?
Consider the different uses of direct-to-consumer genetic tests
Compare the results and platforms provided by different companies
Identify relatives that can be tested to enhance studies of ancestral relationships
The Future of Genetic Testing
Reading: Perfect Genetic Knowledge by Dawn Field
Evaluate the value of personal genetic information relative to its costs
Identify societal impacts of widespread genetic testing
I posted a few times in the summer of 2015 when 23andMe and AncestryDNA both reached the threshold of genotyping their first million customers. I'm consistently amazed at how popular these commercial DNA tests have become. In this year, 23andMe has grown to 2 million customers in the 10 years since launching the first version of their DNA testing service. AncestryDNA now has 5 million customers in their database, adding over 2 million so far this year. The graph below plots the growth of 23andMe and AncestryDNA customers. The graph includes press releases of customer numbers, and also includes customer numbers and test dates from the #Powerof1Million social media campaign that shows a more detailed picture of early growth of the 23andMe database than represented by the press releases. It would be nice to have a similarly fine-grained view of the growth from 1 to 2 million, because the 23andMe product has undergone a lot of changes during this period (e.g. website redesign, carrier status reports, FDA approved health reports). While the addition of the 2nd million 23andMe customers over about a year and a half is remarkable, growth of the AncestryDNA customer database is truly astounding.
To get a better view of growth in the AncestryDNA database, I've dropped the start date in May 2012 and the first reported size of the database (120,000 customers) the following year and plotted customer numbers on a logarithmic scale over about a 3-year period. This does a good job linearizing the exponential growth experienced by the AncestryDNA database since the spring of 2014, which is about the time when I gave tests to my parents. Growth of customer numbers in the first year after introducing the product was a bit lower than it has been over the past 3 years, so the April 2013 number is a bit of an outlier. Remarkably, there does not appear to be any slowdown in the recent growth rate. The time it takes for the database to double in size has been about 10.5 months over this period, so if this trend continues, anticipate that the database will reach a size of 10 million customers in the summer of 2018!
23andMe and AncestryDNA are by far the two largest and well known direct-to-consumer (DTC) genetic testing services, and the sustained growth of the customer bases at both continues against ever increasing competition. MyHeritage recently launched a DNA service to accompany their genealogical platform. Many companies are entering into the health and trait prediction market and working hard to compete. At the Baltimore Ravens football game this weekend, for example, Orig3n is giving away DNA test kits. American, and increasingly international, consumers are clearly interested in the interpretations of DTC genetic testing services. An article by Andelka Phillips that reviewed over 200 DTC genetic services astutely pointed out, "there is also a continuing need for educational initiatives that will allow consumers to understand what test results will mean for them in order to make informed decisions about whether to use such services."
This article discusses why our genome has such a small portion of Neanderthal DNA compared to the amount of DNA from those who originated in Africa. Neanderthals had large skulls with strong hands, while humans in Africa had shorter faces and slender limbs. According to the article, approximately 50,000 years ago these two types of humans encountered one another and started reproducing.
There have been many hypotheses why such a small portion of our genome is Neanderthal in origin. This article proposed an answer that is based on new scientific models and information that hasn't been accessible in the past. The answer is based on two recent studies that overlap enough to give one, scientifically supported answer. This answer is simply that the Neanderthals had a much smaller population than modern humans.
Because Neanderthals had a small population for hundreds of thousands of years, a lot of inbreeding occurred, according to Graham Coop, genetics professor and publisher of one of the studies. This inbreeding caused mutations to develop that negatively impacted their population. These impacts included both superficial mutations, as well as increasing the probability of disease. The article specified that these mutations did not include reproductive issues, which is why the mutations continued to be passed along. A geneticist at 23andMe who worked with Dr. Coop explained that once the two populations began to mix, the ability of natural selection to remove unfavorable mutations in the now unified group began to take place.
David Reich, a genetics professor at Harvard and writer of the other study, found that a majority of Neanderthal DNA was located relatively far away from important genes. This is because in the larger population, natural selection was more able to remove harmful mutations, leaving only mutations that did not significantly impact the well being of the individuals. At first, however, he concluded this was a sign of infertility in Neanderthal-human hybrids, but then determined it couldn't explain most of the pattern. Reich and his team then determined differences in population size was a feasible explanation. Using advanced mathematical models, they determined a "pattern of weak natural selection" could have been the root cause.
The idea of natural selection occurring more efficiently as the two populations mixed makes sense. This is because the idea that the efficiency of natural selection increases as population grows is a general biological principle. This means when it was the relatively small population of only Neanderthals, natural selection would not have been as efficient when compared with the population of both Neanderthals and modern humans.
An article in The Atlantic from September 2015 explores the history of feline modification and asks the question is there a future of genetically improved house cats. The article begins with an excerpt from a Times article from 1885 explaining the genetic research of Francis Galton and his quest to make the perfect house cat, who in Galton's mind should be deaf. The Times went on to say that Galton was impractical and useless when there were so many other things to fix about a cat like it's voice, teeth, and paws. Later in 1981 a task force called the Human Interference Task Force was set up to keep curious humans away from radioactive-waste sights, specifically Yucca Mountain. Some of the philosophers came up with the idea to create cats who's fur would change color when exposed to radiation and create a sort of folklore that insisted cats with colored fur were a bad omen. Obviously this never occurred but the idea of genetically engineered animals was not dead. In 2004 a biotech company Allerca announced their plans to create the first hypoallergenic cat. The cats were on sale for $4,000 but the potential buyers were put through a screening process much like adoption of a child. The company eventually pulled the plug with rumors that the cats were not really hypoallergenic. The most recent genetic expirament occurred in 2011 when a photo of a glowing green cat was released to the public. This cad had been used for feline AIDS testing in hopes of finding a cure for human AIDS. This cat had been injected with monkey genes which prevented the strand of feline AIDS from entering the feline eggs prior to fertilization. As for the green color, the geneticists used jellyfish genes that cause the infected cells to glow an eerie green color. Though this may look like some sort of genetic experiment gone wrong, the researcher assured that their goals were to help take another step in curing AIDS, no creating a generation of glowing, disease-resistant cats. With advancing technology felines may be a part of the future to help find cures for genetic diseases. On the domestic side no current research is being done on "improving" the modern house cat. Along with the lack of research genetic engineering on animals for mass production and consumption comes with a large moral and political debate that may take years to sort out. This may put a damper on those who wish to have hypoalergenic glowing cats but hopeful many research breakthroughs will make up for it on the other side.
A recent article from Nature reports the Chinese scientists have been the first to inject humans with genes edited by the CRISPR-Cas9 technique. On October 28th a team of oncologists at Sichuan University injected the modified cells into a patient with aggressive lung cancer as a part of a clinical trial. Though this is not the first time oncology clinical trials have used edited cells it is the first time with the new and significantly more efficient CRISPR technique This new method will hopeful speed up the race to get gene-edited cells in to clinics across the world. One scientist has predicted a sort of "Sputnik 2.0" with the race being a biomedical duel between the United States and China. With competitive research occurring these studies usually come to marked quicker and the end product is better than had the field been less competitive. The U.S. will soon be using the new technology in a cancer trial that is predicted to start in early 2017. Another Chinese trial is expected to begin in March 2017 specifically focusing on bladder, renal, and prostate cancers. Neither of these trials have approval or funding yet. Specifics about the trial in China were included and began with researchers removing immune cells from a cancer infected patient. They would then use CRISPR, which combines a DNA-cutting enzyme with a molecular guide that can be programmed to tell the enzyme precisely where to cut, to disable a gene in the immune cell. The specific gene they were disabling usually puts a stop to the immune response, a trait cancers can take advantage of to continue proliferating. After the gene splicing the cells were cultivated and injected back into patient. The hope is that with that specific gene blacked that the cells will be able to fight off and defeat the cancer. The Chinese team plans on treating ten people with this method who will each receive two, three, or four injections. For six months these patients will be monitored for any adverse effects and to see if they are benefiting from the treatment. Oncologists across the world are excited for this study and are looking froward in hopes of bettering and saving more lives.