title: Comprehensive mutation analysis of 17 Y-chromosomal short tandem repeat polymorphisms included in the AmpFlSTR Yfiler PCR amplification kit.
abstract: The Y-chromosomal short tandem repeat (Y-STR) polymorphisms included in the AmpFlSTR Yfiler polymerase chain reaction amplification kit have become widely used for forensic and evolutionary applications where a reliable knowledge on mutation properties is necessary for correct data interpretation. Therefore, we investigated the 17 Yfiler Y-STRs in 1,730-1,764 DNA-confirmed father-son pairs per locus and found 84 sequence-confirmed mutations among the 29,792 meiotic transfers covered. Of the 84 mutations, 83 (98.8%) were single-repeat changes and one (1.2%) was a double-repeat change (ratio, 1:0.01), as well as 43 (51.2%) were repeat gains and 41 (48.8%) repeat losses (ratio, 1:0.95). Medians from Bayesian estimation of locus-specific mutation rates ranged from 0.0003 for DYS448 to 0.0074 for DYS458, with a median rate across all 17 Y-STRs of 0.0025. The mean age (at the time of son's birth) of fathers with mutations was with 34.40 (+/-11.63) years higher than that of fathers without ones at 30.32 (+/-10.22) years, a difference that is highly statistically significant (p < 0.001). A Poisson-based modeling revealed that the Y-STR mutation rate increased with increasing father's age on a statistically significant level (alpha = 0.0294, 2.5% quantile = 0.0001). From combining our data with those previously published, considering all together 135,212 meiotic events and 331 mutations, we conclude for the Yfiler Y-STRs that (1) none had a mutation rate of >1%, 12 had mutation rates of >0.1% and four of <0.1%, (2) single-repeat changes were strongly favored over multiple-repeat ones for all loci but 1 and (3) considerable variation existed among loci in the ratio of repeat gains versus losses. Our finding of three Y-STR mutations in one father-son pair (and two pairs with two mutations each) has consequences for determining the threshold of allelic differences to conclude exclusion constellations in future applications of Y-STRs in paternity testing and pedigree analyses.
authors.affiliation: Department of Forensic Molecular Biology, Erasmus University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam The Netherlands.
authors.forename: Miriam
authors.initials: M
authors.lastname: Goedbloed
authors.forename: Mark
authors.initials: M
authors.lastname: Vermeulen
authors.forename: Rixun N
authors.initials: RN
authors.lastname: Fang
authors.forename: Maria
authors.initials: M
authors.lastname: Lembring
authors.forename: Andreas
authors.initials: A
authors.lastname: Wollstein
authors.forename: Kaye
authors.initials: K
authors.lastname: Ballantyne
authors.forename: Oscar
authors.initials: O
authors.lastname: Lao
authors.forename: Silke
authors.initials: S
authors.lastname: Brauer
authors.forename: Carmen
authors.initials: C
authors.lastname: Krüger
authors.forename: Lutz
authors.initials: L
authors.lastname: Roewer
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Lessig
authors.forename: Rafal
authors.initials: R
authors.lastname: Ploski
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Dobosz
authors.forename: Lotte
authors.initials: L
authors.lastname: Henke
authors.forename: Jürgen
authors.initials: J
authors.lastname: Henke
authors.forename: Manohar R
authors.initials: MR
authors.lastname: Furtado
authors.forename: Manfred
authors.initials: M
authors.lastname: Kayser