Large-scale pedigree analysis highlights rapidly mutating Y-chromosomal short tandem repeats for differentiating patrilineal relatives and predicting their degrees of consanguinity

Arwin Ralf*, Diego Montiel Gonzalez, Dion Zandstra, Bram van Wersch, Nefeli Kousouri, Peter de Knijff, Atif Adnan, Sofie Claerhout, Mohsen Ghanbari, Maarten H. D. Larmuseau, Manfred Kayser*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Rapidly mutating Y-chromosomal short tandem repeats (RM Y-STRs) were suggested for differentiating patrilineally related men as relevant in forensic genetics, anthropological genetics, and genetic genealogy. Empirical data are available for closely related males, while differentiation rates for more distant relatives are scarce. Available RM Y-STR mutation rate estimates are typically based on father-son pair data, while pedigree-based studies for efficient analysis requiring less samples are rare. Here, we present a large-scale pedigree analysis in 9379 pairs of men separated by 1-34 meioses on 30 Y-STRs with increased mutation rates including all known RM Y-STRs (RMplex). For comparison, part of the samples were genotyped at 25 standard Y-STRs mostly with moderate mutation rates (Yfiler Plus). For 43 of the 49 Y-STRs analyzed, pedigree-based mutation rates were similar to previous father-son based estimates, while for six markers significant differences were observed. Male relative differentiation rates from the 30 RMplex Y-STRs were 43%, 84%, 96%, 99%, and 100% for relatives separated by one, four, six, nine, and twelve meioses, respectively, which largely exceeded rates obtained by 25 standard Y-STRs. Machine learning based models for predicting the degree of patrilineal consanguinity yielded accurate and reasonably precise predictions when using RM Y-STRs. Fully matching haplotypes resulted in a 95% confidence interval of 1-6 meioses with RMplex compared to 1-25 with Yfiler Plus. Our comprehensive pedigree study demonstrates the value of RM Y-STRs for differentiating male relatives of various types, in many cases achieving individual identification, thereby overcoming the largest limitation of forensic Y-chromosome analysis.

Original languageEnglish
Pages (from-to)145-160
Number of pages16
JournalHuman Genetics
Issue number1
Early online date3 Oct 2022
Publication statusPublished - Jan 2023

Bibliographical note

Funding Information:
This study was funded by the Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Funding Information:
The authors are grateful to all participants of all cohort studies. We thank Cornelia van Duijn and Ben Oostra for setting-up the Erasmus Rucphen Family (ERF) study, P. Veraart for help with sorting out the genealogy records, Jeannette Vergeer and P. Snijders for help in retrieving the materials needed to analyze Cohort 1. We additionally thank Jan Geypen for sample collection and follow-up for Cohort 2. Ronny Decorte is acknowledged for useful comments on the manuscript.

Publisher Copyright:
© 2022, The Author(s).


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