CSE 291 Personal genomics for bioinformaticians Class meetings

CSE 291: Personal genomics for bioinformaticians Class meetings: TR 3: 30 -4: 50 MCGIL 2315 Office hours: M 3: 00 -5: 00, W 4: 00 -5: 00 CSE 4216 Contact: mgymrek@ucsd. edu Today’s schedule: • 3: 30 -4: 00 – Genetic Genealogy + Crowd Genomics • 4: 00 -4: 05 – break • 4: 05 -4: 50 – Surname Inference Journal club Announcements: • Guest lecture by Cinnamon Bloss on Thursday! • PS 2 due Thursday (how is it going? ) • Small schedule rearrangements – check online

Genetic Genealogy + Web 2. 0 Genomics CSE 291: Personal Genomics for Bioinformaticians 01/24/17

Outline • Intro to genetic genealogy + maternal and paternal lineages • Y chromosome analysis • Web 2. 0 genomics

Intro to genetic genealogy

Genetic genealogy is a major personal genomics application

A genetic genealogist’s toolkit Autosomal DNA • SNP genotyping (e. g. 23 and. Me, 1. 5 million SNPs), eventually whole genome sequencing (all 3 billion base pairs) • Can determine recent relatives (e. g. siblings, aunts/uncles, grandparents) • Y chromosome Can determine. DNA overall ancestry decomposition (paternal lineage) • STR genotyping (e. g. FTDNA), Y-SNP analysis (23 and. Me, FTDNA), Y chromosome sequencing (Big. Y) • Determine ancestry along paternal lineage Mitochondrial DNA (maternal lineage) • mt. DNA SNPs (23 and. Me, FTDNA) • Determine ancestry along maternal lineage

Review: how the genome is inherited mt. DNA chr. X chr 1 chr. X chr. Y mt. DNA chr. Y and mt. DNA don’t have recombination! Inherited as one big (easy to analyze) chunk Exceptions: pseudoautosomal region (PAR) on X and Y can recombine

Paternal Lineage – Y chromosome Males share a Y chromosome (minus mutations) with: • Their sons • Their fathers • Their male siblings • Nth cousins that can trace a male line back to the same common ancestor Co-inheritance of surnames and last names! E. g. : Johnson Smith Females don’t have a Y chromosome, so don’t share it with anyone.

Example – 23 and. Me

Maternal Lineage – mt. DNA Females share mt. DNA (minus effects of mutation and mosaicism) with: • Their children • Their mothers • Their siblings • Nth cousins that can trace a female line back to the same common ancestor Males share mt. DNA with: • Their siblings • Their mothers • Nth cousins on the same maternal line

Example – 23 and. Me

Maternal, paternal, autosomal inheritance Founders … Y mt. DNA Y: Paternal lineage mt. DNA: Maternal lineage Autosomal: all ancestral lineages Y mt. DNA

Y chromosome analysis

Y-STRs and Y-SNPs Y-STRs: short tandem repeats on the Y chromosome Example: DYS 458 • Reference genome contains 16 copies of “TTTC” • Example genome (Craig Venter) contains 17 copies of “TTTC” Common Y-STR panels type 12, 67, or 111 markers (more markers = better resolution) Y-STR haplotype: ordered results of number of repeats at each marker Y-SNPs: common single nucleotide polymorphisms on the Y chromsome Example: M 173 (173 rd SNP documented by the Human Population Genetics Laboratory at Stanford, which uses code “M”. ) (modern nomenclature: rs 2032624, chr. Y: 15026424)

Y Haplogroups Nomenclature #1 (by subclade) • Major clades are labeled with capital letters A (base) through R • One or more specific mutations defines the branch points • Subclades within a capital letter group are named using alternative alphanumeric symbols. * used for parent. • E. g. E* contains E 1, E 2, E 3 • E*1 contains E 1 a, E 1 b, etc • It can get crazy. E. g. R 1 b 1 a 2 a 1 a 1 b 3 Nomenclature #2 (by mutation) • Keep capital letter names • Include a dash and mutation name. If multiple mutations, choose one e. g. Alon’s Y haplogroup: R 2 a, or R-M 124 The Y Chromosome Consortium, Genome Research 20

The entire Y Haplotype tree “Y chromosome Adam” (~200 -300 Kya) Poznik et al. Nature Genetics 2016

Surnames and Y chromosomes Smith Y Closely matching Y chromosomes are likely to share a surname Smith Y

Surname Projects http: //clandonaldusa. org/

Calculating TMRCA of a pair of Y chromosomes Common application: Given a pair of Y chromosomes, how many generations ago do they share a common ancestor? (time to most recent common ancestor = TMRCA) If t is small (<~20), likely to share a surname MRCA (most recent common ancestor) t(# generations) Present-day sample 1 Present-day sample 2

Calculating TMRCA of a pair of Y chromosomes t Let: X = x 1, x 2, x 3, … xn Where xi is 1 if vi=ui, else 0. And qi(t) be the probability that marker i matches after t generations: Given: Two Y-STR haplotypes with n markers: V = v 1, v 2, v 3, … v n U = u 1 , u 2 , u 3 , … un qi(t) = (1 -μi)2 t L(x|t) = Πiqi(t)xi(1 -qi(t))1 -xi Example P(t|k) for with 5 markers scored with k matches Mutation rates (# mutations/generation) for each STR: μ = μ 1, μ 2, μ 3, …μn Walsh Genetics 2001

Y-Search

Y-STRs confirm written and oral history

Genghis Khan and Y-STRs 1 in 200 men are direct Y descendants of Genghis Kha Zerjal et al. AJHG 200

Web 2. 0 Genomics

Exploring your genome on the internet 23 and. Me • SNP genotyping + ancestry, trait, and some health tools National Genographic Project • SNP genotyping, focused on human history Family Tree DNA • SNP genotyping, Y-STR and Y-SNP, mitochondrial DNA. land • Free site where you can upload genotypes from e. g. 23 and. Me or FTDNA and get additional analyses and tutorials • Donate your genome to scientific research GENI. com • Build your pedigree and connect with others • Available in analyzable format from familinx. org. Largest connected pedigree = 13 million people! Gedmatch. com • DNA and genealogical tools for researchers and genealogists And many more…