wfgs. 23andmeby jerry merritt explain the problems with autosomal dna tests. provide a tour of a...
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WFGS
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Autosomal DNA
23andMeby
Jerry Merritt
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Explain the problems with Autosomal DNA
tests.
Provide a tour of a 23andMe autosomal account.
Show how to handle the chaos.
Objectives
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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
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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
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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.
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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.
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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
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One way to remember which is which: SNP P=Past STR R=Recent So it’s the SNPs which mark the Haplogroups.
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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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Y Chromosome Mitochondrial DNA (mtDNA) X Chromosome Autosomal DNA
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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
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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
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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.
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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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Y Chromosome Mitochondrial DNA (mtDNA) X Chromosome Autosomal DNA
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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
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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.
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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.
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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.
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Recombination
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Interphase
Homologous pair of chromosomesin diploid parent cell
Chromosomesreplicate
Homologous pair of replicated chromosomes
Sisterchromatids Diploid cell with
replicated chromosomes
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Interphase
Homologous pair of chromosomesin diploid parent cell
Chromosomesreplicate
Homologous pair of replicated chromosomes
Sisterchromatids Diploid cell with
replicated chromosomes
Meiosis I
Homologouschromosomesseparate
1
Haploid cells withreplicated chromosomes
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Interphase
Homologous pair of chromosomesin diploid parent cell
Chromosomesreplicate
Homologous pair of replicated chromosomes
Sisterchromatids Diploid cell with
replicated chromosomes
Meiosis I
Homologouschromosomesseparate
1
Haploid cells withreplicated chromosomes
Meiosis II
2 Sister chromatidsseparate
Haploid cells with unreplicated chromosomes
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MITOSIS MEIOSIS
MEIOSIS I
Prophase I
Chiasma
Chromosomereplication
Homologouschromosomepair
Chromosomereplication
2n = 6
Parent cell
Prophase
Replicated chromosome
Metaphase Metaphase I
Anaphase ITelophase IHaploid n = 3
Daughter cells ofmeiosis I
MEIOSIS II
Daughter cells of meiosis II
nnnn
2n2n
Daughter cellsof mitosis
AnaphaseTelophase
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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
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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
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Y Chromosome Mitochondrial DNA (mtDNA) X Chromosome Autosomal DNA
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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
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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.
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There is nothing in this test that will tell you
which branch of your family the match is on, however.
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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.
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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.
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Y, mt and,Autosomal DNA
As you can see, our Autosomal DNA is (theoretically) representative of our whole ancestry.
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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?”
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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.
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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.
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how many genetic ancestors we have after a certain number of
generations
1 2 3 4 5 6 7 8 9 10 11 12 13 140
20
40
60
80
100
120
140
2 4 816
32
54
77
98
110120
125125125125
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So how far back do you have to go before you
begin to lose ancestral DNA big time?
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1 2 3 4 5 60
10
20
30
40
50
60
70
80
90
100100 99.9 99.8 99.6
54
0.01
% Probability of Having DNA from All of your Ancestors from a Particular Generation
Passed to Your DNA
Number of Generations Back
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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?
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probability that you will have DNA of a specific ancestor from N generations
ago
1 2 3 4 5 6 7 8 9 10 11 12 13 140
10
20
30
40
50
60
70
80
90
100100 100 100 99 98
85
62
38
22
127
4 2 1
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How do you get started doing your autosomal
testing?
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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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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
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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
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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
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The default is NO SHARING. And HEALTH data is, by default, NOT available
to you until you unlock it.
Your Profile
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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
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The 23andMe Homepage.
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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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Locations of haplogroup H circa 500 years ago
Maternal Haplogroup: H
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Locations of haplogroup R1b1b2 circa 500
years ago
Paternal Haplogroup: R1b1b2a1a2f*
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With Y and mtDNA testing the problem was too few
contacts.
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With Autosomal DNA testing the problem is too
many.
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Taming the Chaos
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99.74%
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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.
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Typically you’re trying to connect to a missing
link.
Define the problem.
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Go in with a plan.
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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.
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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
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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.
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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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Third Cousins
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So I now have segments on chromosomes 4 and 8 that are probably from the parents of the two great-grandmother sisters.
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Comparison
Chromosome
Start point
End pointGenetic distance
# SNPs
Catherine vs. Jerry Merritt
428,000,0
0036,000,00
07.2 cM 1151
Catherine vs. Jerry Merritt
439,000,0
0062,000,00
018.0 cM 3409
Catherine vs. Jerry Merritt
8102,000,
000120,000,0
0012.6 cM 3358
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# rsid chromosome position genotype rs4477212 1 72017 AA rs3094315 1 742429 AA rs3131972 1 742584 GG rs12124819 1 766409 AG rs11240777 1 788822 GG rs6681049 1 789870 CC rs4970383 1 828418 AA rs4475691 1 836671 TT rs7537756 1 844113 AG rs13302982 1 851671 AG rs1110052 1 863421 GG rs2272756 1 871896 AG rs3748597 1 878522 CC rs13303106 1 881808 AA rs28415373 1 883844 CC rs13303010 1 884436 AG rs6696281 1 892967 TT
Or you can download your entire genome
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# rsid chromosome position genotype rs28698289 Y 57437890G rs2334088 Y 57438752A rs6568298 Y 57439116T rs4047343 Y 57440310G rs6568295 Y 57440901G rs2334083 Y 57441719C rs9724556 Y 57442197C i4001200 MT 3 T i4001110 MT 7 A i4001358 MT 9 G i4000553 MT 26 C i4001079 MT 40 T i4001190 MT 41 C i4000964 MT 43 C i4001177 MT 46 T i4000987 MT 49 A
Even Y and mtDNA
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Jerry Vicki Catherine
1325 AA 1325 AG 1325 AA3491 AA 3491 AA 3491 AA13123 AG 13123 AG 13123 AA148867 TT 148867 TT 148867 TT166995 AA 166995 AG 166995 AA188239 GG 188239 GG 188239 GG284477 AG 284477 AG 284477 AG284486 AG 284486 AG 284486 AG284489 GG 284489 AG 284489 AG284494 AG 284494 AG 284494 AG284495 CC 284495 CT 284495 CT284500 AA 284500 AG 284500 AG285776 CT 285776 CC 285776 CT285790 TT 285790 TT 285790 TT
And make enormous Excel studies.
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