1.  WFGS

2. 23andMeby Jerry Merritt

3.   Explain the problems with Autosomal DNA tests.  Provide a tour of a 23andMe autosomal account.  Show how to handle the chaos. Objectives

4.   Y-chromosome (paternal line)  Mitochondrial or mtDNA (maternal line)  Autosomal DNA (all lines) There are now three different DNA tests available to gather information about one's ancestry

5.   The Y chromosome is only found in males, who have one Y chromosome and one X chromosome. The Y chromosome is composed of 58 million base pairs and contains 83 genes which code for only 23 proteins.  The Y chromosome does not undergo recombination during meiosis. Y-chromosome

6.   The Y chromosome contains two types of ancestral markers. Short Tandem Repeats (STRs) trace recent ancestry.  The second type of ancestral marker, SNPs, document ancient ancestry. SNPs are small "mistakes" that occur in DNA and are passed on to future generations.  SNP mutations are rare. They happen at a rate of approximately one mutation every few hundred generations.

7.   SNPs (single nucleotide polymorphisms)  STRs (short tandem repeats, aka microsatellites).  SNPs are a change in a single nucleotide in the DNA and occur infrequently; once they occur they are stable and typically define a whole chromosome and become its signature.  STRs change by the number of repeats and change at a much faster rate than SNPs.

8.   By testing the combination of SNPs and STRs in our Y-DNA, we can gain information on our paternal ancestry, ranging from ancient history (thousands and tens of thousands of years ago) with the much slower mutating SNPs, to recent history (100-1000 years ago) with faster mutating STRs.  More simply, SNPs allow us to track ancient or deep ancestry,  while STRs allow us to track recent ancestry in the range of immediate family history over several generations

9.   One way to remember which is which:  SNP P=Past  STR R=Recent  So it’s the SNPs which mark the Haplogroups.

10.   When a SNP occurs it marks a branch in the Y- chromosome phylogenetic tree.  The branch points in the tree are called haplogroups.  The tree has twenty main branches.  They are classified by the letters A through T.  Each branch has many further sub-branches called subclades Haplogroups

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12.   Y Chromosome  Mitochondrial DNA (mtDNA)  X Chromosome  Autosomal DNA

13.   Mitochondria are cellular organelles that provide most of the energy required for various cellular functions.  human mtDNA is a circular molecule of 16,569 base pairs.  Every human cell contains between 100 and 10,000 copies of mitochondrial DNA Mitochondrial DNA

14.   Mitochondria are cellular organelles that provide most of the energy required for various cellular functions.  human mtDNA is a circular molecule of 16,569 base pairs.  Every human cell contains between 100 and 10,000 copies of mitochondrial DNA Mitochondrial DNA

15.   mtDNA analysis is complicated by the fact that not all mitochondria within an organism or even a single cell have exactly the same mtDNA sequence.  In general the most useful genealogical purpose for mtDNA is to try to solve specific puzzles or hypotheses about unproven relationships.

16.   Unlike nuclear DNA, mitochondrial DNA does not recombine and thus there is no change between parent and child.  mtDNA is only passed on from mother to child  although males inherit mtDNA from their mothers, they do not pass it on to their children.  This allows mtDNA to be used for tracing matrilineage.

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18.   Y Chromosome  Mitochondrial DNA (mtDNA)  X Chromosome  Autosomal DNA

19.   The use of X chromosomes to study genealogical relationships is still relatively new.  The X chromosome, just like the Y, contains STRs, called X-STRs.  The problem with studying X-STRs is that the entire X chromosome undergoes recombination during meiosis. X chromosomes

20.   The X chromosome, found in both males and females, is more than 153 million base pairs and contains roughly 1000 genes. Females have two X chromosomes while males have just one.  In other words, in females, the two X chromosomes randomly swap information and genes.

21.   A male’s X chromosome is inherited from his mother.  It is a mixture of her two X chromosomes, one from her mother and one from her father. It is therefore a mixture of the maternal grandparent’s X chromosomes.

22.   A female inherits one X chromosome from each of her two parents.  The X chromosome from her father is passed on from his mother and is a mixture of her parent’s (the paternal great-grandparent’s) DNA….  while the X chromosome from the female’s mother is a mixture of her parent’s (the maternal grandparent’s) DNA.

23.  Recombination

24.  Interphase Homologous pair of chromosomes in diploid parent cell Chromosomes replicate Homologous pair of replicated chromosomes Sister chromatids Diploid cell with replicated chromosomes

25.  Interphase Homologous pair of chromosomes in diploid parent cell Chromosomes replicate Homologous pair of replicated chromosomes Sister chromatids Diploid cell with replicated chromosomes Meiosis I Homologous chromosomes separate 1 Haploid cells with replicated chromosomes

26.  Interphase Homologous pair of chromosomes in diploid parent cell Chromosomes replicate Homologous pair of replicated chromosomes Sister chromatids Diploid cell with replicated chromosomes Meiosis I Homologous chromosomes separate 1 Haploid cells with replicated chromosomes Meiosis II 2 Sister chromatids separate Haploid cells with unreplicated chromosomes

27.  MITOSIS MEIOSIS MEIOSIS I Prophase I Chiasma Chromosome replication Homologous chromosome pair Chromosome replication 2 n = 6 Parent cell Prophase Replicated chromosome Metaphase Metaphase I Anaphase I Telophase I Haploid n = 3 Daughter cells of meiosis I MEIOSIS II Daughter cells of meiosis II n n n n 2n2n 2n2n Daughter cells of mitosis Anaphase Telophase

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29.   If it weren’t for recombination, we would only have 44 ancestors in our genetic tree….  Because we only have 22 pairs of autosomes of which there are 44 halves.  So the least each ancestor could have contributed would be one half of an autosome.  But recombination mixes the genes up.  The outcome is that we have about 125 ancestors in our genetic tree. Recombination Saves the Day

30.   Crossover  Because you end up with swapped alleles from both maternal and paternal grandparents in each chromosome you can’t use that ( by itself ) to trace lineage. Recombination

31.   Y Chromosome  Mitochondrial DNA (mtDNA)  X Chromosome  Autosomal DNA

32.   Now for the good stuff.  Autosomal DNA is the 22 pairs of non-sex chromosomes found within the nucleus of every cell. Autosomal DNA tests examine SNPs, or alleles, located throughout all of your DNA. Autosomal DNA

33.   Autosomal DNA tests can be used to search for relative connections along any branch of your family tree….  … unless the connection is so far back that the shared DNA has essentially been eliminated through too many generations of recombination. Your autosomes are composed of random combinations of your ancestor's autosomes.

34.   There is nothing in this test that will tell you which branch of your family the match is on, however.

35.   Therefore, having your parents and/or grandparents tested as well will definitely help you to narrow down potential matches.  For instance, if you find a match to a particular segment and your mother also matches on that segment, it came from her line.  Likewise for the grandparents.

36.   The Autosomal DNA contains most of the DNA that makes us who we are. Because of the way it is transferred down the generations, we usually cannot identify which specific ancestor gave us specific genes…  unless we compare our results with people we know we are related to, and see which stretches of DNA match.

37.  Y, mt and,Autosomal DNA As you can see, our Autosomal DNA is ( theoretically ) representative of our whole ancestry.

38.   One of the most important – and confusing – concepts that people who are new to autosomal testing encounter is the fact that everyone has both a Genetic Tree and a Genealogical Tree.  Your genealogical tree includes every one of your ancestors throughout history.  Your genetic tree, however, only includes those ancestors who were lucky enough to contribute DNA to your genome. So, what do we mean by “theoretically?”

39.   Your parents are absolutely in your genetic tree, as are your grandparents and great-grandparents.  Go back a few more generations, however, and your genealogical ancestors start disappearing from your genetic tree.  Thus, your genetic tree is actually a tiny subset of your genealogical tree.  Further, while a genealogical tree remains constant (an ancestor will always be in a particular genealogical tree), a genetic tree changes with every new generation (that is, some ancestors will fall off the genetic tree with each new generation). Fading away.

40.   on average only about 125 of our 1024 genealogical ancestors at 10 generations (or 11.7%) are our genetic ancestors.  The probability of having DNA from all of your genealogical ancestors at a particular generation becomes vanishingly small very rapidly.  You only have to go back 5 generations for genealogical relatives to start dropping off your DNA tree. Fading away.

41.  how many genetic ancestors we have after a certain number of generations

42.   So how far back do you have to go before you begin to lose ancestral DNA big time?

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44.   What’s the chance you still have any of that ancestor’s DNA in your cells? And what about that favorite or that famous ancestor like Pocahontas or Thomas Jefferson?

45.  probability that you will have DNA of a specific ancestor from N generations ago

46.  How do you get started doing your autosomal testing?

47.   The best deal at the moment seems to be at 23andme.com.  A test of all chromosomes, including mtDNA, is $99.  But it also requires a one year subscription to their web site or another $9 per month.  This comes to a total on $207.  Or you can do a one-time payment of $399 and be paid up forever. 23andMe

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49.   Arrives in about a week.  You spit in a tube, close the top, and shake it for 20 seconds.  Put it in the pre-paid return mailer and send it off. The Kit

50.   The lab checks 1,000,000 markers or SNPs.  Then they send the data to 23andMe for posting.  This took about two weeks for my sample. The Lab

51.   Once the data is loaded, you have the option of sharing all or parts of it or none of it.  This is handled in your Personal Profile which you set up while waiting for your Kit to arrive. Your Profile

52.   The default is NO SHARING.  And HEALTH data is, by default, NOT available to you until you unlock it. Your Profile

53.   Many people use 23andMe just for the health report.  You have to opt in to see your health data since it could be scary.  Then there is a further opt-in to see data on cancer, Altzheimers, and Parkinsons since that is even more scary.  Genealogists sometimes never look at their Health Report at all.  More on the Health Report in a moment. Health Data

54.  The 23andMe Homepage.

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57.   What if that data got out?  The Genetic Information Nondiscrimination Act, or GINA, has passed through Congress and was signed into law on May 21, 2008.  GINA protects Americans from discrimination on the basis of genetic information.  If you believe that. Yikes!

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59.   Locations of haplogroup H circa 500 years ago Maternal Haplogroup: H

60.   Locations of haplogroup R1b1b2 circa 500 years ago Paternal Haplogroup: R1b1b2a1a2f*

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62.  With Y and mtDNA testing the problem was too few contacts.

63.  With Autosomal DNA testing the problem is too many.

64.  Taming the Chaos

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73.   Even with all of this capability, with the exception of the non-Indian connection, I have not been able to link to another relative by a specific line.  What might this mean for you?  What might make the investment in 23andMe useful to you?  Well, as in the Y and mtDNA, you need to have a problem that Autosomal DNA testing can solve.

74.   Typically you’re trying to connect to a missing link. Define the problem.

75.  Go in with a plan.

76.   I had a worst-case scenario.  After 18 years of detailed research….  I didn’t know the father of a great-grandmother.  So I had no surname to try to connect to.  How then do I know if someone on my list of 23andMe relatives is also kin to the missing father? For example.

77.   Identify some segments of DNA that I know come from the missing father.  Then if I connect to someone who has that same segment I’ll know they are also kin to the missing father.  So how do I go about doing that? My plan

78.   Figure out which connections I already have that are also descended from the missing father.  The great-grandmother in question had one sibling and I knew several of her great-grandkids.  Plus I knew several second cousins from my great- grandmother.  That gives me second and third cousins to work with but they have to take the DNA test with me.  Then any DNA segments we all share must be from the missing father or his wife….  Unless we are also kin along some other lines we don’t know about. Putting the plan into action.

79.   So how do I tell if the shared segments are from the missing father or, instead, from the mother – who I’m fairly sure of?  I have to locate someone descended from the mother’s line but not the father’s line. That requires another third or fourth cousin or two.  If those cousins also share one of the segments it means it came from the mother’s line.  If they don’t share it, then it probably came from the missing father.

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81.  Third Cousins

82.  So I now have segments on chromosomes 4 and 8 that are probably from the parents of the two great-grandmother sisters.

83.  ComparisonChromosomeStart pointEnd point Genetic distance # SNPs Catherine vs. Jerry Merritt 428,000,00036,000,0007.2 cM1151 Catherine vs. Jerry Merritt 439,000,00062,000,00018.0 cM3409 Catherine vs. Jerry Merritt 8102,000,000120,000,00012.6 cM3358

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85.   # rsid chromosomepositiongenotype  rs4477212172017AA  rs30943151742429AA  rs31319721742584GG  rs121248191766409AG  rs112407771788822GG  rs66810491789870CC  rs49703831828418AA  rs44756911836671TT  rs75377561844113AG  rs133029821851671AG  rs11100521863421GG  rs22727561871896AG  rs37485971878522CC  rs133031061881808AA  rs284153731883844CC  rs133030101884436AG  rs66962811892967TT Or you can download your entire genome

86.   # rsid chromosomepositiongenotype  rs28698289Y57437890G  rs2334088Y57438752A  rs6568298Y57439116T  rs4047343Y57440310G  rs6568295Y57440901G  rs2334083Y57441719C  rs9724556Y57442197C  i4001200MT3T  i4001110MT7A  i4001358MT9G  i4000553MT26C  i4001079MT40T  i4001190MT41C  i4000964MT43C  i4001177MT46T  i4000987MT49A Even Y and mtDNA

87.  JerryVickiCatherine 1325AA1325AG1325AA 3491AA3491AA3491AA 13123AG13123AG13123AA 148867TT148867TT148867TT 166995AA166995AG166995AA 188239GG188239GG188239GG 284477AG284477AG284477AG 284486AG284486AG284486AG 284489GG284489AG284489AG 284494AG284494AG284494AG 284495CC284495CT284495CT 284500AA284500AG284500AG 285776CT285776CC285776CT 285790TT285790TT285790TT And make enormous Excel studies.

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