DNA: UNLOCKING THE CODE

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1 DNA: UNLOCKING THE CODE Connecting Cousins for Genetic Genealogy Bryant McAllister, PhD Associate Professor of Biology University of Iowa Iowa Genealogical Society April 9, 2016

2 Workshop Schedule Session 1 Navigating the DNA Marketplace Session 2 Connecting Cousins for Genetic Genealogy Session 3 Option 1: Getting More from Your SNP Data (Advanced) Option 2: Small-Group Tutorials (Beginner) Session 4 Ancestry Analysis from DNA

3 OBJECTIVES Navigate lists of DNA relatives and individual DNA matches Cluster DNA relatives into family groups having common ancestry Recognize patterns of autosomal identity produced by fundamental principles of inheritance

4 Genetic Genealogy DNA-Based Inference of Common Ancestry great grandparents Historical Record of Ancestors great great grandparents great grandparent grandparent parent grandparent parent 2 nd - 3 rd cousins DNA Ancestors DNA Siblings DNA Connections 2 nd cousin 1x removed

5

6 AUTOSOMAL SNP MATCHING DNA matching using segments of identity in SNP data

7 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.

8 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

9 Family Testing Strategy ~50% identical

10 Genome-wide SNP Analysis Each company uses a common testing technology that assesses about 700,000 different known variable sites (SNPs) in the DNA of your genome (including mtdna is some cases). Most of the same sites are used in the tests of different companies.

11 Genome-wide SNP Analysis My mum s hair colour is grey. My mom s hair color is gray.

12 Genome-wide SNP Analysis # rsid chromosome posi-on 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

13 Matching of SNPs # rsid chromosome posi-on 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

14 DNA RELATIVES Clustering DNA relatives through common relationships

15 name name name

16 name name name name

17 name name

18 DNA Matches in AncestryDNA

19 Without an active Ancestry.com subscription

20 With an active Ancestry.com subscription

21 DNA Matches in AncestryDNA

22 Ancestor(s) Shared with DNA Match

23 DNA Matches in AncestryDNA Thomas F McAllister b Ohio d Louisiana Mary A Diggins b Kentucky d Louisiana

24 A Thomas F McAllister b Ohio d Louisiana Mary A Diggins b Kentucky d Louisiana test A

25 DNA Circles

26 name name name name

27 Match A Match B Match C

28 A B C D E Sara Combs b TN d MO William Lane b TN d AR Match A Match B Match C Match D Match E A B C Matches D & E are likely also connected to this same family.

29 Example Summary of DNA Matches DNA Match In Common With or Shared Match Ancestors (relationship) Match-A Match-B Match-C Match-D G Grandparents GG Grandparents GG Grandparents GGG Grandparents Match-A (2C) self yes yes no Match-B (3C) yes self no yes Match-C (3C) yes no self no Match-D (4C) no yes no self

30 Example Summary of DNA Matches DNA Match In Common With or Shared Match (relationship) Match-A Match-B Match-D Match-C Match-A (2C) self yes no yes Match-B (3C) yes self yes no Match-D (4C) no yes self no Match-C (3C) yes no no self D B A C

31 Mechanisms for Clustering Relatives Shared Matches tab in AncestryDNA Shared matches limited to 4 th cousin and closer to tester Shared matches limited to 4 th cousin and closer of 1 match Sharing results of a DNA test bypasses this limit DNA Circles and New Ancestor Discoveries in AncestryDNA DNA kit linked with shared family tree Dependent on both DNA and Ancestor Information matches In Common With sorting in Family Finder (FTDNA) Use Family Finder Matrix to compare multiple DNA relatives No mechanism for clustering match lists in 23andMe Greatest limitation of 23andMe platform for genealogical research

32

33 AUTOSOMAL INHERITANCE Three fundamental principles govern autosomal transmission

34 Mendelian Principles Segregation Chromosome pairs separate and are transmitted individually and equally to gametes

35 Chromosomal Inheritance

36 Autosomal Inheritance 1:1 segregation each generation ~ expectation ~ % 25% 12.5% 6.25% 3.125%

37 Mendelian Principles Segregation Chromosome pairs separate and are transmitted individually and equally to gametes

38 Mendelian Principles Segregation Chromosome pairs separate and are transmitted individually and equally to gametes Independent Assortment Different pairs of chromosomes sort independently during gamete formation

39 Autosomal Inheritance Recombination Independent assortment and exchange between chromosome pairs forms new genetic combinations

40 Patterns of Inheritance

41 SNP Matching rsid chromosome posi-on Grandchild GP1 GP2 rs GG GG GG rs GG TT TG rs AA GG AG rs AA AG AG rs CC TC TC rs GG AA AG rs TT TT TT 45.8 Mb half-identical segment: at least one common variant at all SNPs in this segment rs CC TC TT rs AC AA AA rs GG GG AG rs CC CC TC rs CC TC TT rs CC TC TT

42 The Autosomal Genome Chromosome Measurements Physical Size basepairs 3 Gbp ~ half the genome 6 Gbp ~ whole genome Genetic Size centimorgans 3,590 cm = all autosomes

43 Segment Matching Between Relatives identical segment

44

45 Expectations for the Inheritance of Identical Matching Autosomal Segments Between Relatives Relationship Genome Identical 1 st cousins 12.50% 2 nd cousins 3.13% 3 rd cousins 0.78% 4 th cousins 0.20% 5 th cousins 0.05% Number of Identical Segment 41.4 segments 14.8 segments 4.8 segments 1.5 segments 0.4 segments Avg. Length of Shared Segment p(none)* Donnelly 21.7 cm cm cm cm cm 0.70 *without detection errors

46

47 GENETICS FOR GENEALOGY Considerations

48 Genetics for Genealogy Results vary dramatically based on individual ancestry and database composition test the oldest generation. American Colonial Ancestry 19 th Century German Migrants to Texas

49 Genetics for Genealogy Results vary dramatically based on individual ancestry and database composition test the oldest generations. American Colonial Ancestry & 1/8 19 th Century Irish Migrants 19 th Century German Migrants

50 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.

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