| STR mutation rates | |
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| Tweet Topic Started: Jul 12 2013, 05:01:00 PM (447 Views) | |
| skywalker | Jul 12 2013, 05:01:00 PM Post #1 |
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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.
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