Steve's Genealogy Blog

At the recent Family Tree DNA 5th International Conference on Genetic Genealogy for Project Administrators, Matthew Kaplan, Associate Staff Scientist in the Division of Biotechnology, and Taylor Edwards, Senior Research Specialist in the Genomic Analysis and Technology Core, both at the University of Arizona, presented a lecture entitled “What’s in a Name…the Current State of Y STR Nomenclature 2009”.

Matt Kaplan

SOURCE: Matt Kaplan (Houston, Harris County, Texas). Photographed by Stephen J. Danko on 15 March 2009.

Taylor Edwards

SOURCE: Taylor Edwards (Houston, Harris County, Texas). Photographed by Stephen J. Danko on 15 March 2009.

When analyzing microsatellites or short tandem repeats (STRs), the most direct way to determine the number of repeats is simply to sequence the STRs. This, however, is not the easiest way to determine the number of repeats. In practice, the STRs and flanking regions are replicated in the polymerase chain reaction (PCR) and the lengths of the products are measured. The lengths of the products are compared to the lengths of standards and the results are obtained more quickly and easily than they would if the STRs were directly sequenced.

The Clinical Science and Technology Laboratory of the National Institute of Standards and Technology (NIST) has generated a Human Y Chromosome Profiling Standard (SRM 2395) that can be used to standardize the analysis of STRs in Y DNA.

In addition, standard methods of naming STRs have been recommended:

• “The repeat sequence motif in STRs should be defined so that the first 5′-nucleotide that can define a repeat motif are used” (Butler et al. 2008).
• “The sequence originally described in the literature of the first public database entry shall become the standard reference (and strand) for nomenclature” (Butler et al. 2008).
• “If a nomenclature is already in use, it is recommended that it should be continued” (Gill et al. 2001).
• “Alleles should be named according to the total number of contiguous variant and non variant repeats determined from the sequence data” (Butler et al. 2008).
• Obtain the null allele if a SNP occurs in the primer set.
• “Intermediate alleles (e.g., 11.1) fall into two classes: an insertion/deletion either (a) within the repeat motif or (b) in the flanking region encompassed by the PCR primer positions” (Butler et al. 2008).

The University of Arizona shares all sequence data with Dr. John Butler at NIST. The goal is to follow the standards in the industry.

The result of these recommendations is that the nomenclature used by Family Tree DNA (FTDNA) will be adjusted to conform to the standard. For example, the repeat in DYS441 will change from CCTT to TTCC, with the consequence that FTDNA must add +1 to the repeat values for DYS441. However over 1/3 of FTDNAs 67 markers are not yet addressed by Butler.

As of now, the values of three Y DNA markers used by FTDNA will change. In addition, FTDNA will begin to include microalleles (decimal values) where they appear.

References:

Butler J.M., M.C. Cline, and A.E. Decker. 2008 Addressing Y-chromosome short tandem repeat allele nomenclature. J. Genetic Geneal. 4:125-148.

Gill P., C. Brenner , B. Brinkmann, B. Budowle, A. Carracedo, M.A .  Jobling, P. de Knijff, M. Kayser, M. Krawczak, W.R. Mayr, N. Morling, B. Olaisen, V. Pascali, M. Prinz, L. Roewer, P.M. Schneider, A. Sajantila, C. Tyler-Smith. 2001 DNA Commission of the International Society of Forensic Genetics: Recommendations on forensic analysis using Y-chromosome STRs. Forensic Sci. Intl. 124:5-10.

Copyright © 2009 by Stephen J. Danko

Doron Behar, postdoctoral fellow in the Hebrew University of Jerusalem, and William Hurst, administrator of the mitochondrial DNA (mtDNA) Haplogroup K Project, discussed the use of mtDNA testing for genealogy and anthropology.

Doron Behar, MD, PhD

SOURCE: Doron Behar, MD, PhD (Houston, Harris County, Texas). Photographed by Stephen J. Danko on 14 March 2009.

William R. Hurst

SOURCE: William R. Hurst (Houston, Harris County, Texas). Photographed by Stephen J. Danko on 14 March 2009.

The mitochondrial genome is a circular unit of DNA with 16569 base pairs numbered according to the Cambridge Reference Sequence (CRS). Two hypervariable segments (HVS-I from bp 16029-16383 and HVS-II from bp 00057-00372) make up the bulk of the control region (bp 16024-00372).

Haplotypes are determined from short tandem repeats (STRs) in HVS-I, and haplogroups are determined from single nucleotide polymorphisms (SNPs) in the coding region of the mitochondrial genome.

GenBank has over 5100 complete mtDNA sequences, 250 of which are from Family Tree DNA (FTDNA). By itself, FTDNA has over 4100 complete mtDNA sequences. These sequences were used in the studies published as Olivieri A, et al. (2006) The mtDNA legacy of the Levantine early Upper Paleolithic in Africa. Science 314:1767-1770 and Behar D., R. Villems, H. Soodyall, J. Blue-Smith, L. Pereira, E. Metspalu, R. Scozzari, H. Makkan, S. Tzur, D. Comas. 2008 The Dawn of Human Matrilineal Diversity. Am. J. Hum. Genet. 82:1130-1140.

The HVS-I mutation rate is about 1 mutation per 20,000 years; the coding region mutation rate is about 1 mutation per 5000 years, and the overall mtDNA mutation rate is about 1 mutation per 4000 years.

Based on analyses of mtDNA, there are four surviving populations in Africa today: the Pygmies, the Khoisan, African non-Pygmy or Khoisan, and non-Africans. About 95% of West Central African Pygmies and 20% of West Central African Bantus belong to the L1c1a clade and can be dated to about 75,000 years before the present (ybp). The L0d and L0k clades correspond to Khoi or San ancestry and date back to 90,000 ybp. Clades L3M and L3N gave rise to the entire out of Africa lineage.

A detailed study of one of these out of Africa lineages, designated as Haplogroup K, was conducted based on full mtDNA sequences. Haplogroup K was distributed throughout western Eurasia and is the haplogroup to which about 1/3 of all Ashkenazi Jews belong. Currently, there are 43 K subclades. Based on the full mtDNA sequences obtained, 88 new K subclades have been identified for a total of 131 total K subclades.

Full mitochondrial sequences provide data that can identify new SNPs and, therefore, establish new subclades. The identification of new mtDNA subclades may enable genetic genealogists to provide more refined information on ancestry than is currently available through mtDNA analysis.

Copyright © 2009 by Stephen J. Danko

At the recent Family Tree DNA 5th International Conference on Genetic Genealogy for Project Administrators, Robert D. McLaren presented a talk entitled “Lessons Learned from Running a Large Surname DNA Project.”

Robert D. McLaren

SOURCE: Robert D. McLaren (Houston, Harris County, Texas). Photographed by Stephen J. Danko on 15 March 2009.

Surname projects in genetic genealogy usually require that the project administrator recruit participants. Participants can be recruited by both a shotgun approach and a targeted approach. Shotgun approaches include advertising in family/clan newsletters, surname websites, and surname lists.

To effectively recruit participants, project administrators should create a document for possible recruits that provides a brief overview of the project, including reasons to participate. The document should describe how to join the project and the costs involved.

Project administrators must be prepared to address questions about DNA testing, including medical, privacy, legal, insurance, and non-paternity concerns.

Feedback to members is critical. Project administrators may need to encourage participants to upgrade their tests when appropriate, target distant relatives, and explain results.

Project administrators need to calculate modal haplotypes for each haplogroup. Calculated marker by marker, the modal haplotype represents the most frequent allele at each marker.

Estimating the time to the most recent common ancestor (TMRCA) is a bit tricky. For example, for two participants who match at 65 out of 67 markers, there is a 45% probability that the two share a common ancestor within four generations, and an 84% probability that the two share a common ancestor within eight generations. Still, the TMRCA calculations are designed for populations, not individuals. Two participants who match at 65 out of 67 markers may be much more closely or much more distantly related than predicted by TMRCA calculations.

If the project includes three descendants of a common ancestor, an ancestral haplotype may be estimated (if the possibility of parallel and back mutations is ignored).

Robert McLaren also had several suggestions for Family Tree DNA:

• Report fractional markers,
• Generate a new standard panel of fast and medium-fast mutating markers (30 would be great),
• Include all makers (standard and advanced) in Y-Search, and
• Rework advanced panels of markers so they don’t overlap standard panels.

Copyright © 2009 by Stephen J. Danko

At the recent Family Tree DNA 5th International Conference on Genetic Genealogy for Project Administrators, Dr. Michael Hammer of the University of Arizona discussed advances in calculating the time to the most recent common ancestor (TMRCA).

Michael Hammer, PhD

SOURCE: Michael Hammer, PhD (Houston, Harris County, Texas). Photographed by Stephen J. Danko on 15 March 2009.

Microsatellites or short tandem repeats (STRs) in DNA were first discovered in the 1980s. Genetic genealogists compare the lengths of these STRs present in the Y-chromosome of two individuals in order to estimate the TMRCA.

Several models have been developed over the years to estimate the TMRCA:

• The Symmetric Single Step Model (Ohta T. and M. Kimura, 1973 A model of mutation appropriate to estimate the number of electrophoretically detectable alleles in a genetic population. Genet. Res. 22:201-204.)
• The Asymmetric Mutation Model (Walsh J.B., 1987 Persistence of tandem arrays: implications for satellite and simple-sequence DNAs. Genetics 115:553-567.)
• Multiple Step Models (DiRienzo A., A.C. Peterson, J.C. Garza, A.M. Valdes, M. Statkin et al., 1994 Mutational processes of simple-sequence repeat loci in human populations. Proc. Natl. Acad. Sci. USA 91:3166-3170; Fu Y.-X., and R. Chakraborty, 1998 Simultaneous estimation of all the parameters of a stepwise mutation model. Genetics 150:487-497.)
• The Proportional Slippage Model (Kruglyak S., R. Durrett, M.D. Schug, and C.F. Aquadro, 1998 Equilibrium distributions of microsatellite repeat length resulting from a balance between slippage events and point mutations. Proc. Natl. Acad. Sci. USA 95:10774-10778; Ellegren H., 2000 Microsatellite mutations in the genome: implications for evolutionary inference. Trends Genet. 16:551-555)

Different STRs mutate at different rates, and different lengths of STRs mutate at different rates. In general, the longer the STR, the faster the mutation rate.

Watkins’ Geometric Geometric Model uses four parameters to estimate TMRCA:

• STRs mutate with the probability μ
• STRs mutate up or down with the probability ρ
• STRs mutate in multisteps with the probability α
• STRs mutate with allele-specific mutations with the probability β

When provided with defined pedigrees and STR data, genetic genealogists attempt to calculate the values of μ, ρ, α, and β that are most likely.

Mike Hammer described a method to estimate these parameters for single copy STRs by measuring the number of mutations for each STR and calculating the mutation rate μ for each STR. More mutations are recovered from STRs with more meioses. Close relatives help estimate the α parameter.

These four parameters can be calculated for each STR. In the panels of Y chromosome markers offered by Family Tree DNA, there are both fast and slow changing markers. Panel #2, as a whole, is faster moving than Panel #1, and Panel #3, in general, is faster moving than Panel #2.

The calculation of TMRCA will continue to be refined as more data is collected.

See Watkins J.C. 2007 Microsatellite evolution: Markov transition functions for a suite of models. Theor. Popul. Biol. 71:147-159 for a more detailed discussion of models of STR mutation rates.

Copyright © 2009 by Stephen J. Danko

I just returned home from the Family Tree DNA 5th International Conference on Genetic Genealogy for Project Administrators held in Houston this past weekend.

Staff of Family Tree DNA and the Hammer Lab

SOURCE: Staff of Family Tree DNA and the Hammer Lab (Houston, Harris County, Texas). Photographed by Stephen J. Danko on 15 Mar 2009.

The weekend passed so quickly! I have to admit that I felt a bit awed by both the presenters and the other participants. The Family Tree DNA Project Administrators at this conference were an impressively knowledgeable and dedicated group of genealogists.

It’s late, and I’ll have to leave my comments and observations on the conference until another day. Nonetheless, I’ll be thinking about what I learned for days to come.

Copyright © 2009 by Stephen J. Danko

Today I’m flying to Houston to attend the Family Tree DNA 5th International Conference on Genetic Genealogy for Project Administrators.

I’m the administrator to the Danko DNA Project and the Niedzialkowski DNA Project at Family Tree DNA . These projects are small right now and I hope to learn some techniques to help convince more people to participate.

The conference promises to be an exciting combination of scientific presentations and practical discussions on the use of DNA in genealogy.

The program begins tonight with a reception hosted by Family Tree DNA. The talks begin Saturday morning and continue through Sunday afternoon.

Saturday’s program begins with introductions by Max Blankfeld, Vice-President of Marketing and Operations and Family Tree DNA, followed by a presentation on Family Tree DNA in 2008 by Bennett Greenspan, the President and CEO of Family Tree DNA.

Also on Saturday morning, Spencer Wells, National Geographic Explorer-in-Residence and director of the Genographic Project, will discuss Deep Ancestry: Inside the Genographic Project.

Other presentations during the weekend will discuss Privacy & Ethics of DNA Testing, Advances in mtDNA, Advances in TMRCA (time to most recent common ancestor), the Current State of Y STR (short tandem repeat) Nomenclature 2009, and Updates to the Y-Chromosome Tree, among others.

This will be an exciting conference for me, especially given my scientific background and my compassion for genealogy.

And, if there’s anyone out there with the Niedzialkowski or Danko surnames who is interested in having their DNA analyzed for genealogical purposes, let me know. I can arrange an incredible deal on DNA testing through the Danko DNA Project and Niedzialkowski DNA Project!

Copyright © 2009 by Stephen J. Danko