1. The Personal Genome Navigating the DNA Marketplace
Bryant McAllister, PhD
Associate Professor of Biology
University of Iowa
The Triangle Club
February 18, 2018

2. The Personal Genome
Recreational Genetics – analyses of individual DNA sequence data to inform geographic ancestry, biological relationships and physical/behavioral traits through direct-to-consumer (DTC) genetic tests.
Personalized Medicine – analyses of individual DNA sequence data to diagnose genetic causation of a medical condition and/or tailor medical treatment under guidance of a physician and supported by other medical services.
Define Genome _ the entirety of DNA sequence information present in each of your cells, and shared among the cells of your body
First Human Genome Sequence completed in 2003 – a reference for you, but different
Recreation Genetics – use of your own, or family members, genetic data to inform geographic origins, biological relationships, physical/behavioral traits
Different from Personalized Medicine – use of your genetic data to diagnose or treat diseases
1) How many are familiar with direct-to-consumer genetic tests? Show hands
2) Keep hands raised if you have done a test yourself, or manage the test of a family member
3) Keep hands raised if you have done multiple tests on yourself, or manage multiple tests

3. Introduced in November 2007 at $999
Introduced in November 2007 at $999. Price dropped to $299 in May 2012, and reduced again to $99 in December 2012.

5. DNA Interest Group Meetings: 4th Tuesday of each month, 6-7 pm
Iowa City Public Library, Room A
February 27 – Race & Ancestry
March 27 – Why the Y Chromosome
April 24 – National DNA Day
May 23 – Pharmacogenetics

6. Personal Genome Learning Center
Mission: foster knowledge of genetic and evolutionary principles through engagement with personal genomics
Engage students in the application of genetic and evolutionary principles through the exploration of personal genome data.
Involve students in public outreach events and workshops that support understanding of personal genome results and applications.
Develop resources that support learning genetic and evolutionary principles relevant to understanding personal genome data.

7. Three of the major players in the direct-to-consumer genetic testing marketplace.
Ask: How many have done a test by one of these three companies?

8. Genome-wide SNP Analysis: Major Testing Options
23andMe – Report revised in Includes Ancestry Estimates & DNA Matching ($99 list); Carrier Status & Trait Prediction reports also available ($199 list).
AncestryDNA – Includes Ancestry Estimate and DNA Matching ($99 list). Integrated with Ancestry.com family tree for an extra subscription fee.
MyHeritageDNA – Includes Ancestry Estimate and DNA Matching ($99 list). DNA matches on same platform as tree-building infrastructure.
Family Tree DNA – Various tests available including Family Finder SNP test ($79 list).

9. Long standing interest in the science, technology and applications in “recreational genetics”
A little over a year ago, I proposed to offer a first-year seminar course on personal genomics, including an opportunity for students to do a test on themselves, and then set out to learn what was offered by the different companies.
First, parents given AncestryDNA tests
Tested myself using the Geno2.0 kit from The Genographic Project; finding – I’m basically a brit with a bit of Native American mixed in.

10. Genome-wide snp analysis
Now, I want to turn the attention to genetic test of your whole genome. If you have ever seen a news story with the title of, “genes associated with” or “genes identified that cause” its likely that this is a discovery enabled by the same or similar testing platform you can pay $99 to have your own genome analyzed.
Chromosomes, DNA, and your unique genetic profile

11. DNA is the Cellular Recipe for Life
A Genome is the entire set of DNA molecules present in a cell.
Each DNA molecule contains a string of A=T pairs and G≡C pairs as a DNA sequence.
Cells of an individual contain the same genome sequence, but different from any other individual.
In the case of mitochondrial DNA, it about 16,000 pairs of A-T and G-C bases. Change in the bases of mtDNA through mutation, thus changes in DNA sequence is relatively slow, so your mtDNA sequence is likely the same as your mothers, and her mothers, but as you move back through the generations changes will have accumulated in your lineage compared to others in this room.

12. The Human Genome Chromosomes:
23 pairs of linear DNA molecules inherited from both parents; 22 pairs of autosomes, and a single pair of sex chromosomes
Gametes (egg or sperm) contain only 1 member of each pair

13. The Human Genome Chromosomes:
23 pairs of linear DNA molecules inherited from both parents; 22 pairs of autosomes, and a single pair of sex chromosomes
Gametes (egg or sperm) contain only 1 member of each pair

14. Single Nucleotide Polymorphism
SNP Analysis
Single Nucleotide Polymorphism
My mum’s hair colour is grey.
My mom’s hair color is gray.

15. Single Nucleotide Polymorphism
SNP Analysis
Single Nucleotide Polymorphism
My mom’s hair color is gray.
My mom’s hair color was gray.

16. Genome-Wide SNP Analysis
Each company uses a common testing technology that assesses about 600,000 different known variable sites (SNPs) in the DNA of your genome (including mtDNA in some cases). Most of the same sites are used in the tests of different companies.

17. Genome-Wide SNP Analysis
# rsid chromosome position genotype
rs AA
rs AG
rs CC
rs AA
rs GG
rs AG
rs AC
rs CT
rs AG
rs GG
rs CC
rs TT
rs GG
i GG
i GG
rs GG

18. Ancestry composition
Now, I want to turn the attention to genetic test of your whole genome. If you have ever seen a news story with the title of, “genes associated with” or “genes identified that cause” its likely that this is a discovery enabled by the same or similar testing platform you can pay $99 to have your own genome analyzed.
Predicting the geographic origins of your ancestors

19. Prediction of Ancestry CompositionG
Given an individual with this genotype, what geographic areas is the person likely from?

20. These two tests are the most different in the sites analyzed
These two tests are the most different in the sites analyzed. Results here are from the same person.

22. Uni-Parental Inheritance
Maternal Transmission of mtDNA
Paternal Transmission of the Y chromosome
I’ll return to mtDNA haplogroups later in the talk. I’ve had my own mtDNA sequenced, and frankly it’s not that interesting or informative.
I do hope, however, you have an appreciation of how the analysis of the mtDNA sequence can be used to identify relationships between you and others, and that the relationships identified through analysis of mtDNA only represent a single line of ancestry; mom to mom to mom.
Now I want to turn to another single line of ancestry, the paternal line. Early successes in the analysis of mtDNA to determine relationships in humans were immediately complemented with analyses of the Y chromosome, which traces paternal lineages. Although, analysis of the Y chromosome is only applicable to males, it is broadly used in recreational genetics.

23. Uni-Parental Haplogroups
Both 23andMe and Genographic Project predict haplogroup for mtDNA and Y chrom (for males) using SNPs on these DNAs

24. Y Chromosome Tree

26. DNA Relatives Revealing common ancestry through DNA matching
Now, I want to turn the attention to genetic test of your whole genome. If you have ever seen a news story with the title of, “genes associated with” or “genes identified that cause” its likely that this is a discovery enabled by the same or similar testing platform you can pay $99 to have your own genome analyzed.
Revealing common ancestry through DNA matching

27. Segment Matching Between Relatives
identical
segment
Focusing on a single pair of chromosomes, this diagram illustrates the reduction in the length of a chromosome region inherited from a single ancestor. Exchange between pairs of chromosomes, which can occur each generation, reduces the size of regions inherited from ancestors. The 1st cousins in this diagram each inherited regions of this chromosome from their common grandfather. The brackets encompass an identical segment shared between the cousins in the overlapping region.
Exchange between chromosome pairs gradually reduces the size of regions inherited from ancestors; however, segregation can result in the loss of identity with ancestors. At the 2nd cousin level of this diagram, the grandfather’s chromosome region is transmitted in the lineage on the left, whereas it is lost in the lineage on the right. Segregation produces a 50:50 chance of retention and loss of ancestral chromosome regions each generation.
These processes occur independently across each of the 22 pairs of autosomes. Considering all 22 pairs of autosomes and the amount of exchange within these pairs, full 1st cousins with two common grandparents are expected to share 41 identical segments, on average. The expected number of identical segments shared between full 2nd cousins drops considerably to only 15.

28. at least one common variant at all SNPs in this segment
Matching of SNPs
# rsid chromosome position Tester Match
rs AA GG
rs GG AG
rs CC CC
rs AA AA
rs GG GG
rs GG AG
rs AA AC
rs TT CT
rs GG AG
rs GG GG
rs CC CT
rs GG TT
rs GG GG
i GG GG
i GG GG
rs AA GG
Half-Identical:
at least one common variant at all SNPs in this segment

29. Genetics for Genealogy
Results vary dramatically based on individual ancestry and database composition – test the oldest generation.
American Colonial
Ancestry
19th Century German
Migrants to Texas
Two females, both born about 1940

30. Genetics for Genealogy
Results vary dramatically based on individual ancestry and database composition – test the oldest generation.
American Colonial
Ancestry &
1/8 19th Century
Irish Migrants
19th Century German
Migrants
Their children, both born in late 1960’s

31. Genetics for Genealogy
Results vary dramatically based on individual ancestry and database composition – test the oldest generation.
Endogamy increases the background level of relatedness among individuals.
Lists of DNA matches contain two types of errors:
The genetic identity shared with the relative was not inherited from your most common ancestor(s), but rather a more distant ancestor.
Relatives descended from a known common ancestor(s) do not appear in the list of DNA relatives.
DNA relatives may be connected through multiple pathways of common ancestry.

32. Family Testing Strategy
Test my (and my mother’s) mtDNA; and my dad’s mtDNA
Currently conducting a test on distant cousin that should share my Y chromosome
Also, testing the Y from a cousin of my mothers to examine my maternal grandfathers patriline
~50%
identical

33. Genetics for Genealogy: Major Testing Options
AncestryDNA ($99 list) – Fully integrated with active Ancestry.com tree with powerful features; no ability to directly examine matching DNA segment(s)
MyHeritageDNA ($99 list) – Detailed information on genetic basis of DNA matches; DNA matches exist on site for building family trees (accepts raw data from 23andMe or AncestryDNA)
Family Finder Test at Family Tree DNA ($79 list) – Broad set of features to examine DNA matches; website navigation challenging and database relatively small (accepts raw data from 23andMe or AncestryDNA)
23andMe ($199 or $99) – Good for broad set of interpretations, entertainment, & validating relationships; most users are private and not motivated by genealogy

34. Traits
Now, I want to turn the attention to genetic test of your whole genome. If you have ever seen a news story with the title of, “genes associated with” or “genes identified that cause” its likely that this is a discovery enabled by the same or similar testing platform you can pay $99 to have your own genome analyzed.
Inference of personal characteristics influenced by your genetic profile

40. Considerations
Now, I want to turn the attention to genetic test of your whole genome. If you have ever seen a news story with the title of, “genes associated with” or “genes identified that cause” its likely that this is a discovery enabled by the same or similar testing platform you can pay $99 to have your own genome analyzed.

41. informed decisions about whether to use such services.”
“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.”

42. Questions About DNA Tests
What outcome(s) do you want in the test results?
What does the DNA test assay?
What interpretations are delivered in the results?
How would you use these results?
What is the cost, and how does it compare with competitors?
Are there additional fees associated with access or use of test results?
Are other customers satisfied with the service?
Are the terms of service acceptable to you?

44. Potential Consequences of the Results from a Personal Genetic Test
Surprising findings about family relationships
New relatives discovered by genetic matching
Discovery of genetic relationship between your parents
Different relationship than expected with other tested family members
Surprising prediction of ancestry composition
Individuals contain a genetic mixture representative of their ancestry through human history
Surprising discovery of genetic susceptibility to disease
You and/or your children may have an increased chance of developing an incurable genetic disease