Mutability of Y-chromosomal microsatellites: rates, characteristics, molecular bases, and forensic implications.
Nonrecombining Y-chromosomal microsatellites (Y-STRs) are widely used to infer population histories, discover genealogical relationships, and identify males for criminal justice purposes. Although a key requirement for their application is reliable mutability knowledge, empirical data are only available for a small number of Y-STRs thus far. To rectify this, we analyzed a large number of 186 Y-STR markers in nearly 2000 DNA-confirmed father-son pairs, covering an overall number of 352,999 meiotic transfers. Following confirmation by DNA sequence analysis, the retrieved mutation data were modeled via a Bayesian approach, resulting in mutation rates from 3.78 × 10(-4) (95% credible interval [CI], 1.38 × 10(-5) - 2.02 × 10(-3)) to 7.44 × 10(-2) (95% CI, 6.51 × 10(-2) - 9.09 × 10(-2)) per marker per generation. With the 924 mutations at 120 Y-STR markers, a nonsignificant excess of repeat losses versus gains (1.16:1), as well as a strong and significant excess of single-repeat versus multirepeat changes (25.23:1), was observed. Although the total repeat number influenced Y-STR locus mutability most strongly, repeat complexity, the length in base pairs of the repeated motif, and the father's age also contributed to Y-STR mutability. To exemplify how to practically utilize this knowledge, we analyzed the 13 most mutable Y-STRs in an independent sample set and empirically proved their suitability for distinguishing close and distantly related males. This finding is expected to revolutionize Y-chromosomal applications in forensic biology, from previous male lineage differentiation toward future male individual identification.
Ballantyne
Kaye N
KN
Department of Forensic Molecular Biology, Erasmus University Medical Center Rotterdam, The Netherlands.
Goedbloed
Miriam
M
Fang
Rixun
R
Schaap
Onno
O
Lao
Oscar
O
Wollstein
Andreas
A
Choi
Ying
Y
van Duijn
Kate
K
Vermeulen
Mark
M
Brauer
Silke
S
Decorte
Ronny
R
Poetsch
Micaela
M
von Wurmb-Schwark
Nicole
N
de Knijff
Peter
P
Labuda
Damian
D
Vézina
Hélène
H
Knoblauch
Hans
H
Lessig
Rüdiger
R
Roewer
Lutz
L
Ploski
Rafal
R
Dobosz
Tadeusz
T
Henke
Lotte
L
Henke
Jürgen
J
Furtado
Manohar R
MR
Kayser
Manfred
M
D041322:Chromosomes, Human, Y / Q000235:genetics*; D044707:Forensic Sciences / Q000379:methods*; D056426:Genetic Loci / Q000235:genetics; D005819:Genetic Markers; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010331:Paternal Age
D005819:Genetic Markers
PLoS Biol. 2010 Jan 19;8(1):e1000285
20087410
Forensic Sci Med Pathol. 2009;5(2):77-84
19455440
Nat Genet. 2000 Apr;24(4):396-9
10742105
J Mol Evol. 1997 Apr;44(4):414-21
9089081
Genome Res. 2008 Jan;18(1):30-8
18032720
Hum Mol Genet. 1997 May;6(5):799-803
9158156
Am J Hum Genet. 1998 Jun;62(6):1408-15
9585597
Am J Hum Genet. 2004 Jun;74(6):1183-97
15195656
Hum Mutat. 2005 Dec;26(6):520-8
16220553
Hum Mutat. 2003 Jan;21(1):71-9
12497633
Mol Carcinog. 2009 Apr;48(4):379-88
19306292
Nat Genet. 1996 Aug;13(4):390-1
8696328
Mol Genet Genomics. 2008 Jan;279(1):53-61
17926066
Am J Hum Genet. 2000 May;66(5):1580-8
10762544
Int J Legal Med. 1997;110(3):125-33, 141-9
9228563
Ann Hum Biol. 2007 Mar-Apr;34(2):139-72
17558587
Mol Biol Evol. 2010 Feb;27(2):385-93
19822636
Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):1041-6
9023379
Am J Hum Genet. 1999 May;64(5):1473-4
10205281
Mol Biol Evol. 2009 May;26(5):1093-102
19204044
Mol Biol Evol. 2003 Dec;20(12):2123-31
12949124
Forensic Sci Int Genet. 2009 Sep;3(4):205-13
19647704
Nat Genet. 1998 Nov;20(3):278-80
9806547
BMC Genomics. 2009 Dec 16;10:612
20015383
Genome Res. 2008 Oct;18(10):1545-53
18687880
Genetics. 2004 Sep;168(1):383-95
15454551
Genome Res. 2008 May;18(5):830-8
18385274
Nat Genet. 2001 Sep;29(1):20-1
11528385
Forensic Sci Int Genet. 2011 Jun;5(3):199-201
20457103
Curr Biol. 2000 Oct 19;10(20):1237-46
11069104
Forensic Sci Int Genet. 2007 Jun;1(2):125-8
19083742
Int J Legal Med. 2002 Oct;116(5):289-91
12376840
Science. 2001 Mar 2;291(5509):1738-42
11249819
Genetics. 2003 Jun;164(2):781-7
12807796
Nat Rev Genet. 2003 Aug;4(8):598-612
12897772
Int J Legal Med. 2009 Nov;123(6):471-82
19322579
Genet Res. 1973 Oct;22(2):201-4
4777279
Forensic Sci Int. 2001 May 15;118(2-3):116-21
11311822
Hum Hered. 2008;65(2):91-104
17898540
Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10774-8
9724780
Am J Hum Genet. 2004 Jan;74(1):50-61
14691732
Am J Hum Genet. 2002 Mar;70(3):625-34
11793300
Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8748-53
12070344
Int J Legal Med. 2007 Sep;121(5):359-63
17066276
Nature. 2002 Apr 11;416(6881):624-6
11948348
Genomics. 1991 Jul;10(3):692-8
1716244
Nat Rev Genet. 2004 Jun;5(6):435-45
15153996
Annu Rev Genet. 2007;41:539-64
18076332
J Forensic Sci. 2006 Nov;51(6):1298-314
17199615
Nat Genet. 2000 Nov;26(3):358-61
11062480
Nat Genet. 2000 Apr;24(4):400-2
10742106
Hum Mutat. 2004 Feb;23(2):117-24
14722915
Forensic Sci Int Genet. 2009 Jun;3(3):179-84
19414166