Abstract
Short tandem repeats on the Y-chromosome (Y-STRs) are common DNA polymorphisms useful for genetic genealogy, population and evolutionary genetics, human genetics, pathology and forensic sciences. It is important to identify all Y-STR variants and to have knowledge of Y-STR mutation rates in order to correctly estimate the time to the most recent common ancestor (tMRCA) between paternally related individuals. When capillary electrophoresis (CE) is performed to analyze genealogical pairs, Y-STR sequence variations remain hidden when the number of repeats is identical. These hidden variations could be due to parallel Y-STR changes or modifications (PM) that occur independently in different lineages leading to alleles with identical number of repeats. In this study, we detect for the first time twelve PM by analyzing 133 males (960 meiosis) in extended deep-rooting family pedigrees on 42 Y-STRs. These PM were observed in nine Y-STR loci with mutation rates of at least 5.94 × 10−3 per generation. Sequencing analysis made it possible to distinguish insertions/deletions in different repeat regions revealing the presence of two unique changes in three PM on rapidly mutating and complex Y-STRs DYS724-ab and DYS518. Sequencing unraveled more information concerning the identity of alleles, and increased allelic discrimination possibilities which is of great importance in population genetics and forensic analysis. Limiting the analysis to CE could lead to wrong ancestral allele assumptions, to false negative interpretations and to tMRCA underestimations. These observations highlight the importance and added value of sequencing analysis and suggest a shift in genotyping methods from CE to next generation sequencing.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Tilanus MGJ. Short tandem repeat markers in diagnostics: What’s in a repeat? Leukemia. 2006;20:1353–5.
Brunstein J. STR typing: method and application. Med Lab Obs Mlo. 2014;46:40–2.
Barra GB, Santa Rita TH, Chianca CF, et al. Fetal male lineage determination by analysis of Y-chromosome STR haplotype in maternal plasma. Forensic Sci Int Genet. 2015;15:105–10.
Calafell F, Larmuseau MHD. The Y chromosome as the most popular marker in genetic genealogy benefits interdisciplinary research. Hum Genet. 2017;136:559–73.
Roewer L. Y chromosome STR typing in crime casework. Forensic Sci Med Pathol. 2009;5:77–84.
Kayser M. Forensic use of Y-chromosome DNA: a general overview. Hum Genet. 2017;136:621–35.
Ballantyne KN, Goedbloed M, Fang R, et al. Mutability of Y-chromosomal microsatellites: Rates, characteristics, molecular bases, and forensic implications. Am J Hum Genet. 2010;87:341–53.
Larmuseau MHD, Claerhout S, Gruyters L, et al. Genetic-genealogy approach reveals low rate of extrapair paternity in historical Dutch populations. Am J Hum Biol. 2017;29:1–9.
Claerhout S, Vandenbosch M, Nivelle K, et al. Determining Y-STR mutation rates in deep-routing genealogies: Identification of haplogroup differences. Forensic Sci Int Genet. 2018;34(November 2017):1–10.
Sun JX, Helgason A, Masson G, et al. A direct characterization of human mutation based on microsatellites. Nat Genet. 2012;44:1161–5.
Maguire CN, McCallum LA, Storey C, Whitaker JP. Familial searching: a specialist forensic DNA profiling service utilising the National DNA Database® to identify unknown offenders via their relatives—The UK experience. Forensic Sci Int Genet. 2014;8:1–9.
Chandler JF. Estimating per-locus mutation rates. Journal of Genetic Genealogy. 2006;2:27–33.
Willems T, Gymrek M, Poznik GD, Tyler-Smith C, Erlich Y. Population-scale sequencing data enable precise estimates of Y-STR mutation rates. Am J Hum Genet. 2016;98:919–33.
Ballantyne KN, Ralf A, Aboukhalid R, et al. Toward male individualization with rapidly mutating Y-chromosomal short tandem repeats. Hum Mutat. 2014;35:1021–32:e1007028.
Andersen MM, Balding DJ. How convincing is a matching Y-chromosome profile? PLoS Genet. 2017;13:e1007028.
Børsting C, Morling N. Next generation sequencing and its applications in forensic genetics. Forensic Sci Int Genet. 2015;18:78–89.
Hill CR, Kline MC, Mulero JJ, et al. Concordance study between the AmpFℓSTR® MiniFilerTM PCR amplification kit and conventional STR typing kits. J Forensic Sci. 2007;52:870–3.
Dauber EM, Kratzer A, Neuhuber F, et al. Germline mutations of STR-alleles include multi-step mutations as defined by sequencing of repeat and flanking regions. Forensic Sci Int Genet. 2012;6:381–6.
Rockenbauer E, Hansen S, Mikkelsen M, Børsting C, Morling N. Characterization of mutations and sequence variants in the D21S11 locus by next generation sequencing. Forensic Sci Int Genet. 2014;8:68–72.
Dalsgaard S, Rockenbauer E, Gelardi C, et al. Characterization of mutations and sequence variations in complex STR loci by second generation sequencing. Forensic Sci Int Genet Suppl Ser. 2013;4:e218–9.
Wake DB, Wake MH, Specht CD. Homoplasy: from detecting pattern and mechanism of evolution. Science. 2011;331(April):1032–5.
de Knijff P. Messages through bottlenecks: on the combined use of slow and fast evolving polymorphic markers on the human Y chromosome. Am J Hum Genet. 2000;67:1055–61.
Larmuseau MHD, Vanderheyden N, Van Geystelen A, et al. Recent radiation within Y-chromosomal haplogroup R-M269 resulted in high Y-STR haplotype resemblance. Ann Hum Genet. 2014;78:92–103.
Walsh B. Estimating the time to the most recent common ancestor for the Y chromosome or mitochondrial DNA for a pair of individuals. Genetics. 2001;158:897–912.
Heyer E, Puymirat J, Dieltjes P, Bakker E, De Knijff P. Estimating Y chromosome specific microsatellite mutation frequencies using deep rooting pedigrees. Hum Mol Genet. 1997;6:799–803.
Kayser M, Vermeulen M, Knoblauch H, et al. Relating two deep-rooted pedigrees from Central Germany by high-resolution Y-STR haplotyping. Forensic Sci Int Genet. 2007;1:125–8.
Brinkmann B, Klintschar M, Neuhuber F, Hühne J, Rolf B. Mutation rate in human microsatellites: influence of the structure and length of the tandem repeat. Am J Hum Genet. 1998;62:1408–15.
Gatchel JR, Zoghbi HY. Diseases of unstable repeat expansion: mechanisms and common principles. Nat Rev Genet. 2005;6:743–55.
Pearson CE, Edamura KN, Cleary JD. Repeat instability: mechanisms of dynamic mutations. Nat Rev Genet. 2005;6:729–42.
Brouwer JR, Willemsen R, Oostra BA. Microsatellite repeat instability and neurological disease. Bioessays. 2009;31:71–83.
Pavicevic DS, Miladinovic J, Brkusanin M, et al. Molecular genetics and genetic testing in myotonic dystrophy type 1. Biomed Res Int. 2013;391821:13.
Murillo-Melo NM, Márquez-Quiróz LC, Gómez R, et al. Origin of the myotonic dystrophy type 1 mutation in Mexican population and influence of Amerindian ancestry on CTG repeat allelic distribution. Neuromuscul Disord. 2017;27:1106–14.
Larmuseau MHD, Vanoverbeke J, Van Geystelen A, et al. Low historical rates of cuckoldry in a Western European human population traced by Y-chromosome and genealogical data. Proc R Soc B Biol Sci. 2013;280:20132400.
Acknowledgements
We thank all DNA donors of the genetic genealogy project and Familiekunde Vlaanderen vzw for their participation. Funding was provided by KU Leuven (BOF-C1 grant C12/15/013) and the Fund for Scientific Research – Flanders (FWO-Vlaanderen, research grant number 1503216 N).
Author contributions
Idea and supervision: SC, RD. Sampling and genealogies: SC, MHDL, RD. Genotyping and sequencing: SC, MV, LV. Data analysis: SC. Writing: SC, RD.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Claerhout, S., Van der Haegen, M., Vangeel, L. et al. A game of hide and seq: Identification of parallel Y-STR evolution in deep-rooting pedigrees. Eur J Hum Genet 27, 637–646 (2019). https://doi.org/10.1038/s41431-018-0312-2
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/s41431-018-0312-2
This article is cited by
-
Forensic applications of rapidly mutating Y-STR markers: current status and future perspectives
Forensic Science, Medicine and Pathology (2025)
-
Developmental validation of the STRSeqTyper122 kit for massively parallel sequencing of forensic STRs
International Journal of Legal Medicine (2024)
-
Large-scale pedigree analysis highlights rapidly mutating Y-chromosomal short tandem repeats for differentiating patrilineal relatives and predicting their degrees of consanguinity
Human Genetics (2023)
-
A comprehensive microsatellite landscape of human Y-DNA at kilobase resolution
BMC Genomics (2021)
-
Novel Y-chromosome short tandem repeat sequence variation for loci DYS710, DYS518, DYS385, DYS644, DYS612, DYS626, DYS504, DYS481, DYS447 and DYS449
International Journal of Legal Medicine (2019)
