General Rules for Grade Inquiries:
* The instructor will not respond to inquiries regarding the calculation of grades or questions about adding up scores.
* Grade calculations and additions are performed in Excel once all grades are finalized; students are expected to figure these calculations out independently.
* The instructor will only reply to emails regarding specific grading errors.
Introduction to Genetic Testing and Privacy
Previous Topic Review: Discussion of Hardy-Weinberg analysis and its applications in genetic testing, including:
* Paternity testing.
* Crime scene analysis.
* Conservation biology (deciding which organisms to breed to save a species).
The Importance of Genetic Privacy:
* Concerns revolve around who has access to an individual's genetic data.
* The potential for data leaks or unauthorized sharing and the subsequent harm it could cause.
* 23andMe Consent Policies: When individuals submit a cheek swab, they sign fine print consenting to their genetic data being used for purposes other than their own report. There is a standing question of whether users truly realize the extent of this consent.
The DNA Dragnet and Personal Genomics Databases
DNA Dragnet Definition: Traditionally, a "dragnet" in law enforcement involves the temporary seizure of a large group of individuals to solve a crime.
Legal Requirements for DNA:
* Individual DNA evidence is generally forbidden for seizure without a warrant.
* Law enforcement must have specialized suspicion before data can be mandated.
Voluntary Consent via Commercial Databases:
* Police can request DNA samples from large numbers of people who are not currently detained or arrested, provided consent is obtained.
* Submission of samples to companies like Ancestry.com or 23andMe constitutes voluntary consent, making that data available for law enforcement use in personal genomics databases.
De-identification of Samples:
* Attempts are made to de-identify patient samples in clinical settings.
* UPMC and Geisinger: These organizations have undertaken massive genetic research experiments sequencing thousands of individuals.
* EPIC Database: This is the database used to store patient information; records are kept de-identified to protect privacy from hackers or leaks.
Genetic Exceptionalism and Discrimination:
* The concern is whether employers or insurance companies will use genetic sequences to discriminate against individuals.
* Example: An insurance company might refuse to pay for coverage if an individual is discovered to be heterozygous for Cystic Fibrosis or possesses other genetic markers that carry a negative connotation to the payer.
Commercial Genetic Testing Kits and Data Types
Major Providers: Historically, Ancestry.com and 23andMe are the primary market leaders.
Data Presentation: Results typically include percentages and geographic maps showing ancestral origins. These percentages change over time as the reference population (the sample population compared against the user) grows and provides better data.
Four Types of Data Used in Commercial Testing:
1. Mitochondrial DNA (mtDNA): Used to track maternal lineage (the mother's side of the family).
2. Y-chromosome Haplogroups: Used to track paternal lineage.
* This is only applicable to males (XY).
* Females (XX) cannot track their paternal lineage through this method as they lack a Y-chromosome.
3. Geographic Origins and Ethnicity Estimates: Derived from historical records, such as church records.
4. Autosomal SNPs: Single Nucleotide Polymorphisms found on autosomes (chromosomes 1 through 22).
Concepts in Genetic Genealogy
Definitions:
* Genealogy: The study of a family tree and the descent of individuals through historical records.
* Genetic Genealogy: The practice of layering genetic information (DNA data) on top of traditional genealogical family trees.
Haplogroups:
* A haplogroup is a long stretch of DNA containing different DNA sequences or SNP markers linked together on a chromosome that are inherited as a unit.
* The term "haplo" refers to the haploid nature of the inherited sequence (from one chromosome).
* Haplogroups are used to trace deep ancestry, such as ancient migration patterns out of Africa thousands of years ago.
Haplogroups vs. Haplotypes:
* Haplogroups: Track deep time ancestry (thousands of years).
* Haplotypes: Involve smaller amounts of information and only track ancestry over hundreds of years.
Human Evolutionary Lineages: Mitochondrial Eve and Y-Chromosome Adam
Mitochondrial Eve:
* There are 78 recognized mitochondrial haplogroups for humans.
* The "L" haplogroup includes "Mitochondrial Eve," the woman from whom every female currently on Earth is descended.
* Clarification: This does not mean she was the only woman alive at the time. Other women (metaphorically referred to as Wilma or Betty) existed, but their mitochondrial lineages eventually died out because they did not produce continuous female offspring to carry the DNA to the modern day.
Migration Patterns:
* Lineage "L" originated in Africa.
* The sub-haplogroup "L3" was the lineage that left the African continent to populate the rest of the world, while six other sub-haplogroups remained in Africa.
Y-Chromosome Adam:
* All men on Earth are descended from a single Y-chromosome haplogroup, identified as haplogroup "E".
* Other paternal lineages existed but have since gone extinct.
* There are approximately 20 different Y-chromosome haplogroups currently present on Earth derived from this common ancestor.
The Molecular Clock and Anthropological Research
The Molecular Clock:
* DNA polymerase makes errors during replication at a relatively constant rate.
* By comparing two genome sequences and counting the number of differences, scientists can estimate the time of divergence between those two groups.
* This functions similarly to carbon dating but uses DNA sequences to measure time.
Multidisciplinary Research:
* Molecular anthropologists and archaeologists combine genetic data with physical evidence (like tools, caves, or pottery) to build a more accurate picture of human evolution and migration.
Ethnicity Estimates and Family Lore
Data Reliability: Ethnicity estimates are most reliable when drawn from SNP analysis of autosomes combined with documented family histories spanning at least 5 generations.
Historical Records:
* Mormons: Maintain extensive written records of descendants and marriages.
* Greenland: Possesses comprehensive records of offspring for the history of its population.
* European Churches: Maintain centuries of records regarding marriages and births.
The Fallibility of Family Oral History:
* Families often have "lore" regarding their ancestry that is not supported by genetic data.
* Example: A common myth in Pennsylvania is that families have a certain percentage of Native American ancestry (often a "great grandmother").
* The instructor's own genome sequencing showed 0% Native American ancestry, despite family stories.
* Dialogue Note: A student mentioned using a "trail of tombstones" to verify ancestry for scholarships. The instructor cautioned that while tombstones are helpful, they are not definitive because non-paternity events (affairs, secret adoptions, or siblings raised as children of the grandparents) occurred frequently before DNA testing existed.
Family Tree App: The Mormon-run "Family Tree" app is a free resource that allows users to see tombstone records and ancestral lineages, sometimes dating back to the 1600s in Boston or older.
Forensic Applications and Technology
Analytical Tools:
* CODIS (Combined DNA Index System): The FBI/government database used for forensic analysis. It uses STRs (Short Tandem Repeats).
* STRs: DNA regions where sequences like GATC repeat multiple times (AATG is another example mentioned).
* Commercial Kits: Ancestry.com and 23andMe use SNPs (Single Nucleotide Polymorphisms) and examine nearly 1,000,000 locations on the chromosomes.
Genetic History:
* The first human genome sequence was completed in 2002.
* Early sequencing involved only a few individuals, such as Craig Venter (private project) and a composite of individuals for the public project.
* 1,000 Genomes Project: A subsequent major project to sequence 1,000 individuals to understand genetic variability.
Database Biases: Most current genetic databases are heavily biased toward populations of European descent, with less data available for individuals from Africa, Asia, and Oceania.
Rare SNPs: Mutations that occur in 1 in 1,000 or 1 in 10,000 people are often not captured by these commercial kits, which focus on the most common differences.
Case Studies in Forensic Genetic Genealogy
2012 Hacking Study: Two individuals demonstrated they could use online resources (like 23andMe/Ancestry) to identify participants in the supposedly anonymous "1,000 Genomes Project." They mapped Y-haplogroups to surnames found on social media to identify participants and their families.
The Golden State Killer (Joseph James DeAngelo):
* Crimes: Committed 12 murders, 50 rapes, and numerous robberies between 1976 and 1986.
* Investigation: In 2018, investigators used a rape kit from a 1980 crime to extract DNA.
* Process: They uploaded the crime scene DNA to GEDmatch, a public database where users voluntarily upload their sequence data.
* Finding the Suspect:
1. GEDmatch identified "third cousins" of the killer.
2. Investigator Paul Holes (contextual note) and his team built family trees using newspapers and gravesite records.
3. They narrowed the search to two cousins matching the geographic and age profile.
4. They eliminated one cousin via DNA from a discarded item (napkin/cup) that showed a family match but not a direct match.
5. They surveilled Joseph James DeAngelo and collected facial tissue from his trash.
6. The DNA from the facial tissue matched the rape kit and murder scene evidence.
* Outcome: DeAngelo was taken into custody without a violent confrontation.
Questions & Discussion
Ethics of Genetic Privacy: The lecture concludes by questioning the ethics of using family members' voluntary data to prosecute relatives. Is it ethical to have your DNA data used to identify a family member (e.g., an uncle) who is a serial killer? While many might support catching a violent criminal, it remains a significant ethical dilemma regarding consent and the use of personal information.