Welcome Guest [Log In] [Register]
Add Reply
STR mutation rates
Topic Started: Jul 12 2013, 05:01:00 PM (447 Views)
skywalker
Advanced Member
[ *  *  * ]
Rapidly mutating Y-chromosomal STRs
Kayser M
1,*
,
Ballantyne K
1,2
,
Ralf A
1
, on behalf of the RM Y-STR Study Groupª
1
Department of Forensic Molecular Biology, Erasmus MC University Medical Center Rotterdam, Rotterdam,
Netherlands
2
Forensic Services Departement, Victoria Police, Macleod, Victoria, Australia
Y-chromosomal STRs (Y-STRs) currently applied in forensic analysis provide high but not
maximal resolution in male lineage differentiation and their power to separate male relatives is
low. Consequently, using current marker sets, conclusions from Y-STR analysis usually cannot be
made on the individual level as anticipated in the forensic arena, which represents a major draw
back. However, it would be desirable to combine the advantage of Y-chromosome analysis in
separating male from female DNA components in mixed stain analysis, such as it is essential for
solving cases of sexual assault, with the advantage of autosomal STR analysis in individual
identification, which often is not informative in mixed stain analysis. In order to find rapidly
mutating Y-STRs for differentiating male relatives, we previously performed a large mutation rate
study analyzing 186 Y-STRs in ~2000 father-son pairs and identified a set of 13 markers that
mutate considerably faster than all other loci tested. We recently showed that this set of rapidly
mutating (RM) Y-STRs can differentiate male relatives in a large number of cases (i.e., 67% of
relatives separated by 1-20 generations whereas Yfiler only did 15%). Furthermore, we showed
that RM Y-STRs increase male lineage differentiation considerably (i.e., by 8% from 90.4% with
Yfiler to 98.3% with RM Y-STRs in the worldwide HGDP-CEPH samples). To provide further
prerequisites for forensic applications of RM Y-STRs, and to make the data finally available for
haplotype search in future forensic case work, we now carried out a multicenter study involving 70
institutions from around the world. We collected quality-controlled data for the 13 previously
identified RM Y-STRs from over 10,000 unrelated male individuals; for about 7000 of them
conventional Y-STR data (Yfiler) are available to us for comparative analysis. Furthermore, we
collected RM Y-STR data on >1000 father-son pairs for additional male relative differentiation
testing. In this plenary talk I will summarize the benefits of using RM Y-STRs in forensic analyses
and will provide the first results and conclusions from this multicenter study on behalf of the RM
Y-STR Study Groupª.

Y-STR mutations: what paternity cases can tell us about the relationship between allele
length and mutation rate
Jochens A
1,*
,
Caliebe A
1
,
Roesler U
1
,
Krawczak M
1
1
Christian-Albrechts University, Kiel, Germany
Forensic applications of Y-STR markers often require estimates of the respective mutation rates.
This is especially true for phylogenetic analyses, where mutation rates must be estimated to
calibrate the molecular clock. Usually the locus-specific fraction of observed mutations in a
sample is used for these purposes. However, it is well known that the rate of STR mutation not
only varies across loci, but does also depend on the allele length for any given locus, although the
exact nature of this dependency is still unclear. We describe some simple STR mutation models,
including a novel logistic one, incorporating allele length as a factor [1]. To fit and compare these
models, data on the inheritance of Y-STRs in father-son duos, accumulated from the forensic
literature, were used. For each locus and each model, we employed a maximum likelihood
approach to estimate the model parameters. For most loci considered, a certain version of the
logistic mutation model was found to provide the best fit according to Akaike's Information
Criterion. This implies that the mutation probability at these loci increases non-linearly with allele
length at a rate that differs between upward and downward mutations. [1] Jochens A, Caliebe A,
Roesler U, Krawczak M. Genetics 189(4): 1403-1411, 2011.

Testing Y chromosome STR mutation rates using deep-rooting pedigrees
Erasmus JC
1,*
1
University of Pretoria, Pretoria, South Africa
Y-chromosome STR mutation rates play an important role in forensic sciences, especially for
determining the paternity probability during paternity testing. Mutation rate estimates for
genealogical approaches (like father-son pair typing) normally give a higher mutation rate estimate
than population based studies with a known recent population history. The Afrikaner population
serves as a good system to test the y-chromosome STR mutation rate with a deep-rooting pedigree
approach. Deep-rooting pedigree studies are also useful for estimating the non-paternity rate of a
population. South African founding fathers from Europe often introduced unique surnames into the
Afrikaner population from the mid 1600s to 1700s. South Africa has an active genealogical
research society and records often permit researching an individuals’ pedigree that stretch back to
the founding father. Y-chromosome STR mutation and non-paternity rates were estimated from 20
deep-rooting pedigrees with 6545 meiotic transfers. Subjects that are genealogically connected to
the founding fathers were typed for 17 y-chromosome STR loci with the AmpliflSTR® Yfiler® kit
(Applied Biosystems). A recent surname (Greeff) based study estimated an average STR mutation
rate of 4.85 x 10
-3
based on a single old South African family. We estimated an average STR
mutation rate of 3.1 x 10
-3
and when we combined our data with the Greeff study, we obtained an
average STR mutation rate of 3.5 x 10
-3
. Our mutation rate estimate is higher than the father-son
pair approach (2.8 x 10
-3
), but still falls within the confidence interval limits we obtained. We
estimated a non-paternity rate of 0.51% for the Afrikaner population, which is even lower than the
recent estimate of 0.78% for the Afrikaner population.

Analysis of mutation rates in purported brother pairs with 17 Y-STR loci
Edson SM
1,*
,
Maynard KL
1
1
Armed Forces DNA Identification Laboratory, Dover AFB, United States
Y-STR mutation rates have most commonly been computed between father and son pairings. For
missing persons casework and examination of skeletonized human remains, reference materials
may not be available from the father or son of the decedent. While mitochondrial DNA (mtDNA)
analysis is frequently used, in cases of commingled remains where one or more individuals share a
mitotype, additional genetic means of identification need to be utilized. The Armed Forces DNA
Identification Laboratory (AFDIL) has been examining the use of Y-STR analysis as an addition to
the toolkit of genetic analysis. In the course of validating the use of the AmpFLSTR® Yfiler®
PCR Amplification Kit (Life Technologies) with skeletonized human remains, the need to examine
mutation rates in the presence of increased generational steps was identified. Four hundred
seventy-six individuals were analyzed to determine the mutation rates at 17 Y-STR loci. The
individuals selected were self-reported brothers to missing individuals and also had at least one
other brother available for comparison. Reference materials were obtained in the course of family
reference collections for mtDNA analysis. Sibling indices (both full and half) were determined
using the AmpFLSTR® Identifiler® Kit (Life Technologies) for each pair. Of the 194 alleged
sibling pairs successfully amplified, the majority of individuals were found to be consistent with
their purported brother. However, twenty of these pairs varied from each other by one or two loci,
each by a single repeat. Of note is the finding of thirteen cases of questionable genetic
relationship, including possible non-paternity and non-sibship.

http://dna2012.gerichtsmedizin.at/files/DNA_in_Forensics_2012.pdf
Edited by skywalker, Jul 12 2013, 05:08:12 PM.
Offline Profile Quote Post Goto Top
 
1 user reading this topic (1 Guest and 0 Anonymous)
« Previous Topic · Y-chromosome: CF · Next Topic »
Add Reply