| MUTATION RATE ANALYSIS NOTES - see #3 FTDNA Case Study Framework |
Anatole Klyosov - summary of methods to confirm family trees through mutation rate analysis of clusters
To calculate mutation rates you first need to identify a cluster - a branch of a haplogroup tree with the modal haplotype being the common ancestor. Copying of DNA from father to son can result in mutations in SNPs (occur once and remain) and STRs (short tandem repeat markers that are either shortened or lengthened). The group of STRs are known as haplotypes. The STRs of a common ancestor is known as the modal haplotype of a haplogroup.
Example of mutation rates: in 6 of 12 markers mutations occur at the rate of 1 in 2840 years. In 67 markers, 1 mutation takes place in 170 years. If you are a genetic distance of 2 from 67 markers of the modal haplotype of a haplogroup, chances are that it took 340 years for the mutation to take place.
Markers
DYS Mutations
Ave mutation rate
Ave mutation rate
per haplotype per maker 6 of 12 19, 388, 390, 391, 392, 393 1 in 2840 yrs .0088 .00147 in FTDNA order 12 12 marker panel 1 in 1140 yrs .022 .00183 in FTDNA order 25 25 marker panel 1 in 540 yrs .046 .00184 in FTDNA order 37 37 marker panel 1 in 280 yrs .090 .00243 in FTDNA order 67 67 marker panel 1 in 170 yrs .145 .00216 in FTDNA order In order to find the Time to the Most Recent Common Ancestor (TMRCA), more than one haplotype will be needed: at least
- (40) 6 markers
- ??? 12 markers
- (10) 25 markers
- (4) 67 markers
The smaller the amount of markers or haplotypes included, the less reliable the result. The average STR mutations is used to calculate the time span from the MRCA. Assumption: A generation is 25 years and occurs 4 times in 100 years.
2 Methods:
- Logarithmic - unmutated
- ln (B/A) = kt
- B=total haplotypes in set
- A=number of unchanged base haplotypes in set
- k=average mutation rate
- t=# years
- example
- B= 100, A=80 12 marker haplotypes k =.0088;
- ln (100/80)/.0088 = 250 years
divide by zero error A (number of unchanged base haplotypes in set) can not = 0
- Linear - mutation count
- n/N/μ = t
- n=# mutations
- N=# haplotypes
- μ=average mutation rate
- t=# years
If both methods have approximately the same result this is a 'clean' result
If the methods yield different results, the haplotypes in calculation are probably from a mixed population:
- "The main reasons of such a discrepancy are typically as follows:
different mutation rates employed by researchers,
lack of calibration of mutation rates using known genealogies or known historical events, or when a time depth for known genealogies was insufficient to get all principal loci involved,
mixed series of haplotypes, which are often derived from different clades, and in different proportions between those series, which directly affect a number of mutations in the series,
lack of corrections for reverse mutations (ASD-based calculations [see below] do not need such a correction),
lack of corrections for asymmetry of mutations in the given series of haplotypes – in some cases."
page 190 Mutation Rates and some historical evidence written in the Y Chromosome I. Basic Principals and Method by Anatole Klyosov
- I used the different phylogenetic PHYLIP programs, features and TreeView to find the clusters. If they didn't have a clean result, I realized that not enough haplotypes were being represented. Given the population in the world and the number of the South Irish in my FTDNA projects that I include in the case study the probability for finding family clusters is quite low. For perspective the U.S. population is 312,016,766, FTDNA has 343,915 members and I have 185 South Irish members with a genetic distance less than 9.
Population Calculation
Percentage
FTDNA members vs U.S. population 343,915/312,016,766= .0011 South Irish project members vs FTDNA members 185/343,915= .0005 South Irish FTDNA members vs U.S. population 185/312,016,766= 0.00000059 South Irish FTDNA members vs Irish immigrants during famine 185/2,000,000= 0.0000925 South Irish FTDNA members vs Irish immigrants in U.S. 185/36,278,332= 0.000005099463
Reviewing the percentages above, you can clearly see that the number of project members is quite low and many more results need to be added to build out family trees and branches. As a result the number of 'clean' mutation rate results will be lower than anticipated. The majority of the work will be the in the identification of the clusters using the phylogenetic trees and verifying the relationships using the logarithmic and linear mutation rate calculation methods. The methodology uses the South Irish research of family trees and branches as an example. All other FTDNA projects should have similar numbers in comparison to the total population.
South Irish cluster example (click link to see current working prototype for the MacFarlane project):
Kit Name County Project Haplogroup 393 390 19 391 385 426 388 439 389-i 392 389-ii 458 459 455 454 447 437 448 449 464 460 GATA H4 YCAII 456 607 576 570 CDY 442 438 531 578 DYF395S1 590 537 641 472 DYF406S1 511 425 413 557 594 436 490 534 450 444 481 520 446 617 568 487 572 640 492 565 South Irish Modal 13 24 14 10 11-15 12 12 11 13 13 29 17 9-10 11 11 24 15 19 29 15-15-17-17 11 11 19-23 15 15 18 17 36-37 13 12 11 9 15-16 8 10 10 8 10 10 12 23-23 16 10 12 12 15 8 12 22 20 13 12 11 13 11 11 12 11 128386 Mark R. Donahue 1 E & II IrishII GD 2 Not known O'Donoghue R1b1b2 13 24 14 10 11-15 12 12 11 13 13 29 17 9-10 11 11 24 15 19 29 15-15-15-17 11 11 19-23 15 15 18 17 34-37 13 12 11 9 15-16 8 10 10 8 10 10 12 23-23 16 10 12 12 15 8 12 22 20 13 12 11 13 11 11 12 11 87188 John Winston Donahue 1 E & II IrishII GD 3 O'Donoghue R1b1b2 13 24 14 10 11-15 12 12 11 13 13 29 17 9-10 11 11 24 15 19 29 15-15-17-17 11 11 19-23 15 13 18 17 35-36 11 12 11 9 15-16 8 10 10 8 10 10 12 23-23 16 10 12 12 15 8 12 22 20 13 12 11 13 11 11 12 11 11211 Geoffrey The O'Donoghue Glens 1 E & II IrishII GD 3 Offaly/Glenflesk, Kerry O'Donoghue R1b1b2 13 24 14 10 11-15 12 12 11 13 13 29 17 9-10 11 11 24 15 19 29 15-15-17-17 11 11 19-23 15 15 18 17 36-37 12 12 11 9 15-16 8 10 10 8 10 10 12 23-25 16 10 12 12 15 8 13 22 20 13 12 11 13 11 11 12 11 138667 Connell 1 E & II IrishII GD 4 Ireland O'Connell R1b1b2 13 24 14 10 11-15 12 12 11 13 13 29 17 9-10 11 11 24 15 19 29 15-15-17-17 11 11 19-23 15 15 18 18 36-36 12 12 11 9 15-16 8 10 10 8 10 10 12 23-23 16 10 12 12 15 8 13 22 20 13 12 11 13 11 11 12 11 12294 Donahue, Kerry, Ireland 1 E & II IrishII GD 3 Ireland South Irish & Sullivan R1b1b2 13 24 14 10 11-15 12 12 11 13 13 29 17 9-10 11 11 24 15 19 29 15-15-17-17 11 11 19-23 15 15 18 17 36-38 12 12 11 9 15-16 8 10 10 8 10 10 12 23-23 16 10 12 12 15 8 12 22 20 14 12 11 13 11 11 12 11 Anc Michael B E R Donohue 1 E & II IrishII GD 3 Clonfert O'Donoghue R1b1b2 13 24 14 10 11-15 12 12 11 13 13 29 17 9-10 11 11 24 15 19 29 15-15-17-17 11 11 19-23 15 15 17 17 36-37 12 12 11 9 15-16 8 10 10 8 10 10 12 23-23 16 10 12 12 15 8 13 22 20 13 12 11 13 11 11 12 11 98930 Mortimer O'Donoghue 1 E & II IrishII GD 3 Knocknagoshel, Limerick O'Donoghue R1b1b2 13 24 14 10 11-15 12 12 11 13 13 29 17 9-10 11 11 24 15 19 29 15-15-17-17 11 11 19-23 15 15 18 18 36-37 12 12 11 9 15-16 8 10 10 8 10 10 12 23-23 16 10 12 12 15 8 13 22 20 13 12 11 13 11 11 12 11 52203 Abraham Hayes, b.1727, Fairfield, CT 1 E & II IrishII GD 3 Ireland Eo'ganacht septs R1b1b2 13 24 14 10 11-15 12 12 11 13 13 29 17 9-10 11 11 24 15 19 29 15-15-17-17 11 11 19-23 16 15 19 17 36-39 13 12 11 9 15-16 8 10 10 8 10 10 12 23-23 16 10 12 12 15 8 12 22 20 13 12 11 13 11 11 12 11 87188 John Winston Donahue 1 E & II IrishII GD 3 O'Donoghue R1b1b2 13 24 14 10 11-15 12 12 11 13 13 29 17 9-10 11 11 24 15 19 29 15-15-17-17 11 11 19-23 15 13 18 17 35-36 11 12 11 9 15-16 8 10 10 8 10 10 12 23-23 16 10 12 12 15 8 12 22 20 13 12 11 13 11 11 12 11 48210 John Dennehy 1 E & II IrishII GD 3 Ireland South Irish R1b1b2 13 24 14 10 11-15 12 12 11 13 13 29 17 9-10 11 11 24 15 19 29 15-15-17-17 11 11 19-23 15 13 18 17 35-36 11 12 11 9 15-16 8 10 10 8 10 10 12 23-23 16 10 12 12 15 8 12 22 20 13 12 11 13 11 11 12 11 N3676 Thomas M Donohue* 1 E & II IrishII GD 2 Limerick O'Donoghue R1b1b2 13 24 14 10 11-15 12 12 11 13 13 29 17 9-10 11 11 24 15 19 29 15-15-17-17 11 11 19-23 15 15 18 17 37-37 14 12 11 9 15-16 8 10 10 8 10 10 12 23-23 16 10 12 12 15 8 12 22 20 13 12 11 13 11 11 12 11 168616 Bernard O'Neill 1 E & II IrishII GD 2 Kilkenny O'Donoghue R1b1b2 13 24 14 10 11-15 12 12 11 13 13 29 17 9-10 11 11 24 15 19 29 15-15-17-17 11 11 19-23 15 15 18 17 34-37 13 12 11 9 15-16 8 10 10 8 10 10 12 23-23 16 10 12 12 15 8 12 21 20 13 12 11 13 11 11 12 11 67716 Mahoney 1 E & II IrishII GD 3 Ireland O'Mahony R1b1a2 13 24 14 10 11-15 12 12 11 13 13 30 17 9-10 11 11 24 15 19 29 15-15-16-17 11 11 19-23 15 15 18 17 36-36 13 12 11 9 15-16 8 10 10 8 10 10 12 23-23 16 10 12 12 15 8 12 22 20 13 12 11 13 11 11 12 11 80538 Sullivan 1 E & II IrishII GD 5 Unknown Origin Sullivan 13 24 14 10 11-15 12 12 11 13 14 29 17 9-10 11 11 24 15 19 29 15-15-17-17 11 11 19-23 15 15 18 17 36-38 12 12 11 9 15-16 8 10 10 8 10 10 12 23-23 16 10 12 12 15 8 12 22 20 14 12 12 13 11 11 12 11 181470 O'Mahony 1 E & II IrishII GD 0 Ireland O'Mahony R1b1a2 13 24 14 10 11-15 12 12 11 13 13 29 17 9-10 11 11 24 15 19 29 15-15-17-17 11 11 19-23 15 15 18 17 36-37 13 12 112325 O'Connell of Tarmons 1 E & II IrishII GD 1 Ireland O'Connell R1b1 13 24 14 10 11-15 12 12 11 13 13 29 17 9-10 11 11 24 15 19 29 15-15-17-17 11 11 19-23 15 15 18 17 36-37 12 12 U2516 Sullivan 1 E & II IrishII GD 1 Unknown Origin Sullivan 13 24 14 10 11-15 12 12 11 13 13 29 17 9-10 11 11 24 15 19 29 15-15-17-17 11 11 19-23 15 15 18 17 32-37 13 12 128141 Geoffrey O'Connell b.1825 Ireland 1 E & II IrishII GD 2 Ireland O'Connell R1b1b2 13 24 14 10 11-15 12 12 11 13 13 29 17 9-10 11 11 24 15 19 29 15-15-17-17 11 11 19-23 16 15 18 17 36-37 12 12 How to update 1. insert new row below the last entry mutation rate 12 marker panel 25 marker panel 37 marker panel 2.calculate 12, 25 and 37 marker: fast moving marker changes 12 haplotypes 0.022 2 mutations B total number of haplotypes slow moving marker changes 25 haplotypes 0.046 1 mutations A base haplotypes unchanged shade cells unchanged haplotypes changes 37 haplotypes 0.090 33 changes # changes shade cell changed markers 18 B total haplotypes 16 A base haplotypes 18 B total haplotypes 17 A base haplotypes 18 B total haplotypes 1 A base haplotypes 3.the logarithmic and linear methods automatically calculate. logarithmic method ln (B/A)/mutation rate logarithmic method= 5.35 generations 134 years logarithmic method= 1.24 generations 31 years logarithmic method= 32.12 generations 803 years linear method changes/B total/mutation rate linear method= 5.05 generations 126 years linear method= 0.00 generations 0 years linear method= 20.37 generations 509 years Based on the logarithmic and linear methods for 12 and 25 markers, these 18 haplotypes are in a cluster and are in a family tree. The results of 37 markers indicates that these haplotypes are from different branches of the same family tree.
Resources
Paper - Mutation Rates and some historical evidence written in the Y Chromosome I. Basic Principals and Method - Anatole Klyosov
Paper - DNA Geneaology, Mutation Rates, and Some Historical Evidence written in the Y Chromosome II. Walking the Map - Anatole Klyosov
Additional Papers from Anatole Klyosov's Series
Interpreting Clusters DNA & Genealogy Colleen Fitzpatrick, Andrew Yeiser; see pages ....