Allele Frequency Database Research Articles

Paternity testing and other inference about relationships from DNA mixtures

We present methods for inference about relationships between contributors to a DNA mixture and other individuals of known genotype: a basic example would be testing whether a contributor to a mixture is the father of a child of known genotype. The evidence for such a relationship is evaluated as the likelihood ratio for the specified relationship versus the alternative that there is no relationship. We analyse real casework examples from a criminal case and a disputed paternity case; in both examples part of the evidence was from a DNA mixture. DNA samples are of varying quality and therefore present challenging problems in interpretation. Our methods are based on a recent statistical model for DNA mixtures, in which a Bayesian network (BN) is used as a computational device; the present work builds on that approach, but makes more explicit use of the BN in the modelling. The R code for the analyses presented is freely available as supplementary material.We show how additional information of specific genotypes relevant to the relationship under analysis greatly strengthens the resulting inference. We find that taking full account of the uncertainty inherent in a DNA mixture can yield likelihood ratios very close to what one would obtain if we had a single source DNA profile. Furthermore, the methods can be readily extended to analyse different scenarios as our methods are not limited to the particular genotyping kits used in the examples, to the allele frequency databases used, to the numbers of contributors assumed, to the number of traces analysed simultaneously, nor to the specific hypotheses tested.

Analysis of four PCR/SNaPshot multiplex assays analyzing 52 SNPforID markers

The SNPforID consortium identified a panel of 52 SNPs for forensic analysis that has been used by several laboratories worldwide. The original analysis of the 52 SNPs was based on a single multiplex reaction followed by two single-base-extension (SBE) reactions each of which was analyzed using capillary electrophoresis. The SBE assays were designed for high throughput genetic analyzers and were difficult to use on the single capillary ABI PRISM 310 Genetic Analyzer and the latest generation 3500 Genetic Analyzer, as sensitivity on the 310 was low and separation of products on the 3500 with POP-7™ was poor. We have modified the original assay and split it into four multiplex reactions, each followed by an SBE assay. These multiplex assays were analyzed using polymer POP-4™ on ABI 310 PRISM® and polymers POP-4™, POP-6™ and POP-7™ on the 3500 Genetic Analyzer. The assays were sensitive and reproducible with input DNA as low as 60 pg using both the ABI 310 and 3500. In addition, we found that POP-6™ was most effective with the 3500, based on the parameters that we assessed, achieving better separation of the small SBE products; this conflicted with the recommended use of POP-7™ by the instrument manufacturer. To support the use of the SNP panel in casework in Malaysia we have created an allele frequency database from 325 individuals, representing the major population groups within Malaysia. Population and forensic parameters were estimated for all populations and its efficacy evaluated using 51 forensic samples from challenging casework.

Computational Identification and Characterization of a Promiscuous T-Cell Epitope on the Extracellular Protein 85B of Mycobacterium spp. for Peptide-Based Subunit Vaccine Design.

Tuberculosis (TB) is a reemerging disease that remains as a leading cause of morbidity and mortality in humans. To identify and characterize a T-cell epitope suitable for vaccine design, we have utilized the Vaxign server to assess all antigenic proteins of Mycobacterium spp. recorded to date in the Protegen database. We found that the extracellular protein 85B displayed the most robust antigenicity among the proteins identified. Computational tools for identifying T-cell epitopes predicted an epitope, 181-QQFIYAGSLSALLDP-195, that could bind to at least 13 major histocompatibility complexes, revealing the promiscuous nature of the epitope. Molecular docking simulation demonstrated that the epitope could bind to the binding groove of MHC II and MHC I molecules by several hydrogen bonds. Molecular docking analysis further revealed that the epitope had a distinctive binding pattern to all DRB1 and A and B series of MHC molecules and presented almost no polymorphism in its binding site. Moreover, using “Allele Frequency Database,” we checked the frequency of HLA alleles in the worldwide population and found a higher frequency of both class I and II HLA alleles in individuals living in TB-endemic regions. Our results indicate that the identified peptide might be a universal candidate to produce an efficient epitope-based vaccine for TB.

A genetic overview of Atlantic coastal populations from Europe and North-West Africa based on a 17 X-STR panel

The forensic use of X-STRs requires the creation of allele and haplotype frequency databases in the populations where they are going to be used. Recently, an updated Spanish allele and haplotype frequency database for the new 17 X-STR panel has been created, being the only database available up to now for this new multiplex. In order to broaden the forensic applicability of the 17 X-STR panel, 513 individuals from four different populations located on the Atlantic Coast of Europe and North–West Africa have been studied, i.e. Brittany (France), Ireland, northern Portugal, and Casablanca (Morocco). Allele and haplotype frequency databases, as well as parameters of forensic interest for these populations are presented. The obtained results showed that the 17 X-STR panel constitutes a highly discriminative tool for forensic identification and kinship testing in the studied populations. Furthermore, we aimed to study if these populations located on the Atlantic coast actually share alike allele and haplotype frequency distributions since they have experienced genetic exchanges throughout history. This would allow creating larger forensic databases that include several genetically similar populations for its use in forensic casework. For this purpose, pairwise FST genetic distances between the analyzed populations and others from the Atlantic Coast previously studied with the 17 X-STR panel or the ten coincident markers included in the decaplex of the GHEP-ISFG were estimated. Our results suggest that certain nearby populations located on the European Atlantic coast could have underwent episodes of genetic interchange as they have not shown statistically significant differentiation between them. However, the population of Casablanca showed significant differentiation with the majority of the European populations. Likewise, the autochthonous Basque Country and Brittany populations have shown distinctive allele frequency distributions between them. Therefore, these findings seem to support that the use of independent allele and haplotype frequency databases for each population instead of a global database would be more appropriate for forensic purposes.

Forensic Spanish allele and haplotype database for a 17 X-STR panel

The currently developed 17 X-STR panel (DXS8378, DXS9898, DXS7133, GATA31E08, GATA172D05, DXS6801, DXS7423, DXS6809, DXS6799, DXS7132, DXS9902, DXS6800, DXS6789, DXS10075, DXS10079, DXS6807, and DXS6803) offers a highly discriminative tool for forensic identification and kinship testing. With the aim of providing a global Spanish population X-STR database, we present haplotype and allele frequencies and parameters of forensic interest for the 17 X-STR panel obtained from 593 unrelated individuals from Alicante, Aragon, the Basque Country, Andalusia, Galicia, Madrid, and Barcelona that represent the most populated regions of the Spanish Peninsular territory. The seven populations were compared to test possible population genetic substructures. The lack of significant differences among the studied Spanish populations supports the use of the allele and haplotype frequency database presented herein as a global Spanish population sample useful for statistical evaluation in forensic casework. After conducting the LD plots derived from HapMap and pairwise linkage disequilibrium tests, DXS7132, DXS10075, and DXS10079 markers were included in a cluster and haplotype frequencies were calculated. The improvement in the forensic parameters for the Spanish population using 17 X-STRs in comparison to the previous 10 X-STR allele frequencies database is also shown.

Recommendations of the DNA Commission of the International Society for Forensic Genetics (ISFG) on quality control of autosomal Short Tandem Repeat allele frequency databasing (STRidER)

The statistical evaluation of autosomal Short Tandem Repeat (STR) genotypes is based on allele frequencies. These are empirically determined from sets of randomly selected human samples, compiled into STR databases that have been established in the course of population genetic studies. There is currently no agreed procedure of performing quality control of STR allele frequency databases, and the reliability and accuracy of the data are largely based on the responsibility of the individual contributing research groups. It has been demonstrated with databases of haploid markers (EMPOP for mitochondrial mtDNA, and YHRD for Y-chromosomal loci) that centralized quality control and data curation is essential to minimize error. The concepts employed for quality control involve software-aided likelihood-of-genotype, phylogenetic, and population genetic checks that allow the researchers to compare novel data to established datasets and, thus, maintain the high quality required in forensic genetics.Here, we present STRidER (http://strider.online), a publicly available, centrally curated online allele frequency database and quality control platform for autosomal STRs. STRidER expands on the previously established ENFSI DNA WG STRbASE and applies standard concepts established for haploid and autosomal markers as well as novel tools to reduce error and increase the quality of autosomal STR data. The platform constitutes a significant improvement and innovation for the scientific community, offering autosomal STR data quality control and reliable STR genotype estimates.

Genetic polymorphisms of pharmacogenomic VIP variants in the Mongol of Northwestern China.

BackgroundWithin a population, the differences of pharmacogenomic variant frequencies may produce diversities in drug efficacy, safety, and the risk associated with adverse drug reactions. With the development of pharmacogenomics, widespread genetic research on drug metabolism has been conducted on major populations, but less is known about minorities.ResultsIn this study, we recruited 100 unrelated, healthy Mongol adults from Xinjiang and genotyped 85 VIP variants from the PharmGKB database. We compared our data with eleven populations listed in 1000 genomes project and HapMap database. We used χ2 tests to identify significantly different loci between these populations. We downloaded SNP allele frequencies from the ALlele FREquency Database to observe the global genetic variation distribution for these specific loci. And then we used Structure software to perform the genetic structure analysis of 12 populations.ConclusionsOur results demonstrated that different polymorphic allele frequencies exist between different nationalities,and indicated Mongol is most similar to Chinese populations, followed by JPT. This information on the Mongol population complements the existing pharmacogenomic data and provides a theoretical basis for screening and therapy in the different ethnic groups within Xinjiang.

Abstract P2-09-11: Consistency of pathogenicity determinations for hereditary cancer gene mutations

Abstract Background: As the number of laboratories offering genetic tests grows, the potential for inconsistent variant classifications increases. New resources can help address this: (a) ClinVar, a rapidly growing public database of clinical variants to which many (but not all) laboratories contribute; (b) the public release of thousands of BRCA1/2 reports from Myriad Genetics through the Sharing Clinical Reports Project (SCRP), the Free the Data (FTD) initiative, and recent publications; and (c) ExAC, a greatly improved database of population allele frequencies. These complement longstanding efforts, e.g. the ENIGMA consortium. In addition, the American College of Medical Genetics (ACMG) recently updated guidelines for the interpretation of sequence variants. Using these resources, we sought to investigate the consistency of variant classifications to help inform ongoing practice. Methods: Pathogenicity assessments for variants in hereditary cancer genes were collected from multiple sources. Among these were 15,364 BRCA1/2 submissions to ClinVar, including 5416 submissions from SCRP and 1062 from our prior work [1]. When 3 or more submissions for a variant were available, we determined a consensus interpretation requiring 2 of 3 submitters to agree (or 3 of 4, etc.) to identify outliers. For our own classifications, we established a point-based system based on the 2015 ACMG guidelines, and independently applied it to publicly available evidence of pathogenicity without regard to other labs' classifications. Results: Initially, discordance among ClinVar submissions appears high (20-30%). However, upon investigation much of this discordance is a result of (i) research submissions to ClinVar, (ii) differences in confidence (e.g. benign vs. likely benign), (iii) older data in ClinVar, (iv) single lab outliers, and (v) nuances in the detailed structure of the ClinVar database. A careful comparison using the consensus methodology of objectively filtered ClinVar data shows high concordance between our interpretations and consensus: 95% were identical and 99% were similar (e.g. benign and likely benign were considered similar). Where consensus was not achieved (8% of variants with 3 or more independent sources) or not possible (any variant with only 2 sources), pairwise comparisons showed that few of these remaining differences (5%) were clinically significant. Also, many variants with significant discordances appeared to be particularly rare in the human population, and thus would be present in few patients. The rate of discordances with SCRP/FTD data was similar with that of other ClinVar submitters. Conclusions: Evaluations of inter-laboratory concordance need to be done carefully to avoid over-counting differences. Laboratories generally agree on the clinical significance of the vast majority of variants. Furthermore, the inter-laboratory consensus classification is often reached using a careful implementation of the ACMG guidelines and publicly available data. Thoroughly understanding the remaining differences is challenging when the evidence used by any laboratory is not available for peer review. Detailed data and methods from this study are available for review and alternate analyses. [1] Lincoln et al. SABCS 2014; JMD 2015. Citation Format: Lincoln S, Nykamp K, Kobayashi Y, Yang S, Powers M, Anderson M, Monzon F, Topper S. Consistency of pathogenicity determinations for hereditary cancer gene mutations. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-09-11.

MG-129 Our experience ofin silicogene panel testing for clinically heterogeneous disorders using exome sequencing

Background The implementation of next generation sequencing technology (NGS) in a molecular diagnostics laboratory has resulted in a major transformation in service delivery. The ability to generate accurate sequence data from thousands of genes in a single experiment has facilitated the development of comprehensive gene panel tests for genetically heterogeneous disorders. Previous methodology of gene panel testing included Sanger sequencing, which was time-consuming, labour-intensive and costly and therefore restricted the number of genes that were included in a panel. Methods/results At The Hospital for Sick Children (Toronto, Canada), we have developed and clinically validated in silico gene panels using whole exome sequencing (WES) for several heterogeneous disorders including hereditary spastic paraplegia (HSP), connective tissue and bone disorders (CT), hereditary hearing loss (HL), Noonan syndrome (NS) and autoimmune disorders (AI). Our laboratory’s current strategy of using WES has several advantages including: (1) standardised workflows that facilitate the development of additional gene panels; (2) expansion of current gene panel as new disease associations are discovered; and (3) building of an internal database of allele frequencies to aid in interpretation of variants. Through our validation studies we have shown high reproducibility and accuracy with >99% sensitivity for detection of single nucleotide variants (SNVs) and >95% for detection of small insertion/deletions (indels). Conclusions NGS technologies have enabled our laboratory to expand our testing menu to include genes that comprise part of the differential diagnoses for several disorders which will lead to improved detection rates, increased genetic diagnoses and ultimately better clinical care.

Development and validation of an allelic frequency database for Qatari population using 13 rapidly mutating Y-STRs multiplex assay

Differentiating male lineages using non-recombining Y-chromosomal genetic markers is highly informative for tracing human migration and for forensic studies. Recently, it has been shown that the level of male lineage resolution can be enhanced by analysing rapidly mutating (RM) Y-STRs. The aim of this study was to develop an allelic frequency database for Qatari population to evaluate the resolution power of 13 RM Y-STRs. The overall haplotype diversity (HD) was 100%. It was found that the markers which contributed the most toward high HD were DYF399S1 and DYF403S1a/b. Together with their value for paternal male relative differentiation, these RM Y-STRs will be a valuable asset for forensic casework. AMOVA test was performed between Qatari population in comparison to Gulf countries, Middle East, and several worldwide population data sets. FST values were also calculated. Geography was found to account considerably for the pattern of population sub structuring. The RM Y-STR markers showed remarkable haplotype resolution power in the Qatari population, high gene diversity and sufficient robustness for a diverse range of applications.

Autosomal indels distribution in Metropolitan Manila, Philippines

The Philippines are a group of islands in the Asia-Pacific region harboring a high diversity of cultures, languages and people due to various migration waves and different degrees of admixture between neighboring groups. In this work we studied the most populous region of the country – Metropolitan Manila – with a set of small autosomal insertion deletion (indel) polymorphisms, to assess their genetic diversity and usefulness in forensic context. Using a single-tube multiplex reaction we characterized 38 indels in 195 individuals born in the National Capital Region, allowing to establish an allele frequency database for future reference in forensic applications. The genetic diversity observed was high (average heterozygosity=0.40890), similar to previous studies in other East Asian populations, and the marker set reached good levels of informativeness, with a combined power of discrimination of 99.999999999997% and combined power of exclusion of 99.50%. In conclusion, our study showed that this simple indel multiplex can be useful for forensic applications in Metropolitan Manila Filipino population.

Statistical and population genetics issues of two Hungarian datasets from the aspect of DNA evidence interpretation

When the DNA profile from a crime-scene matches that of a suspect, the weight of DNA evidence depends on the unbiased estimation of the match probability of the profiles. For this reason, it is required to establish and expand the databases that reflect the actual allele frequencies in the population applied. 21,473 complete DNA profiles from Databank samples were used to establish the allele frequency database to represent the population of Hungarian suspects. We used fifteen STR loci (PowerPlex ESI16) including five, new ESS loci. The aim was to calculate the statistical, forensic efficiency parameters for the Databank samples and compare the newly detected data to the earlier report. The population substructure caused by relatedness may influence the frequency of profiles estimated. As our Databank profiles were considered non-random samples, possible relationships between the suspects can be assumed. Therefore, population inbreeding effect was estimated using the FIS calculation. The overall inbreeding parameter was found to be 0.0106. Furthermore, we tested the impact of the two allele frequency datasets on 101 randomly chosen STR profiles, including full and partial profiles. The 95% confidence interval estimates for the profile frequencies (pM) resulted in a tighter range when we used the new dataset compared to the previously published ones. We found that the FIS had less effect on frequency values in the 21,473 samples than the application of minimum allele frequency. No genetic substructure was detected by STRUCTURE analysis. Due to the low level of inbreeding effect and the high number of samples, the new dataset provides unbiased and precise estimates of LR for statistical interpretation of forensic casework and allows us to use lower allele frequencies.

Allele frequencies of microsatellite loci for genetic characterization of a Sicilian bovine population.

Short tandem repeats are used as an effective method to trace DNA markers in genotyping. Using a standardized kit, we tested 11 microsatellite markers recommended by the International Society for Animal Genetics (ISAG) in a sample of 495 Sicilian cattle. The aim of this study was to investigate the allele frequencies in the Sicilian cattle population to provide a reference database and at the same time to assess the use of the ISAG microsatellite panel for pedigree analysis. DNA samples were collected from blood and amplified in an 11-plex polymerase chain reaction (PCR); PCR products were injected in a 3130 Genetic Analyzer. All loci showed high mean polymorphism information content (0.768), and the observed mean heterozygosity was less than the expected value (0.732 vs 0.794, respectively). The exact test for Hardy-Weinberg proportions, allele number, and inbreeding coefficient were calculated. Our results indicated that equilibrium was not always maintained. The observed mean homozygote value exceeded the expected value (132.81 vs 102.14), but no evidence for allele dropout was found. These results could be explained by a non-random mating; further studies using a larger number of animals could confirm or invalidate this hypothesis. The probability of identity and exclusion of a locus were also estimated and proved to be useful in paternity testing. The ISAG microsatellite panel is useful to screen the Sicilian bovine kinship. Currently, an allele frequency database is being constructed.

Genetic diversity between two Igbo men from Owerri senatorial province as determined by autosomal short tandem repeats, Y-chromosomal short tandem repeats and mitochondrial DNA typing methods

Background: Human identification has recently been optimized following the completion of human genome sequence, by using DNA markers that exhibit the highest possible variation. However, in developing countries such as Nigeria, the application of DNA typing for identification of human subjects either for forensic or medical purposes is inadequate due to the absence of national forensic DNA laboratories and lack of the legislative framework. Materials and Methods: In this study, two male subjects of Igbo origin provided their blood, hair and buccal samples for DNA analysis. DNA was extracted, purified, quantified with human quantifiler™ polymerase chain reaction reaction mix. Hyper-variable segment 1 of the D-loop mitochondrial DNA (mtDNA HVS-1) was amplified, purified and fragments sequenced and analyzed with ABI Genetic Analyzer. A multiplex AmpFlSTR Identifiler kit amplified 15 STR plus amelogenin loci of the nuclear DNA and 16 STR of the Y-chromosome. GeneMapper ID software version 3.2 was used for the analysis of autosomal and Y-chromosome AmpFlSTR. Results: Result show that the mtDNA lineage of UMBACK subject belongs to L3e2b while ELAMBIA is assigned to L3f1b1 haplogroup. Based on the allelic frequency database, both subjects displayed uniqueness in random match probability for the autosomal allelic short-tandem repeat (STR). Based upon a mutation rate of 0.003 for Y-DNA STR markers, the two individuals most likely shared a common paternal ancestor 96 generations ago. Both subjects were assigned to E1b1a haplogroup with a 100% probability, which is consistent with the haplogroup associated with Igbo people in Nigeria. Conclusion: As expected, well-established forensic genetic tools comprising of mtDNA, autosomal and Y-chromsomomal STR typing methods were all found to distinguish two selected Nigerian Igbo individuals with a very high power of discrimination.

Choice of population database for forensic DNA profile analysis.

When evaluating the weight of evidence (WoE) for an individual to be a contributor to a DNA sample, an allele frequency database is required. The allele frequencies are needed to inform about genotype probabilities for unknown contributors of DNA to the sample. Typically databases are available from several populations, and a common practice is to evaluate the WoE using each available database for each unknown contributor. Often the most conservative WoE (most favourable to the defence) is the one reported to the court. However the number of human populations that could be considered is essentially unlimited and the number of contributors to a sample can be large, making it impractical to perform every possible WoE calculation, particularly for complex crime scene profiles. We propose instead the use of only the database that best matches the ancestry of the queried contributor, together with a substantial FST adjustment. To investigate the degree of conservativeness of this approach, we performed extensive simulations of one- and two-contributor crime scene profiles, in the latter case with, and without, the profile of the second contributor available for the analysis. The genotypes were simulated using five population databases, which were also available for the analysis, and evaluations of WoE using our heuristic rule were compared with several alternative calculations using different databases. Using FST = 0.03, we found that our heuristic gave WoE more favourable to the defence than alternative calculations in well over 99% of the comparisons we considered; on average the difference in WoE was just under 0.2 bans (orders of magnitude) per locus. The degree of conservativeness of the heuristic rule can be adjusted through the FST value. We propose the use of this heuristic for DNA profile WoE calculations, due to its ease of implementation, and efficient use of the evidence while allowing a flexible degree of conservativeness.

The variability in likelihood ratios due to different mechanisms.

Recently there has been a drive towards standardisation of forensic DNA interpretation methods resulting in the uptake of probabilistic interpretation software. Some of these software solutions utilise Markov chain Monte Carlo techniques (MCMC). They will not produce an identical answer after repeat interpretations of the same evidence profile because of the Monte Carlo aspect. This is a new source of variability within the forensic DNA analysis process. In this paper we explore the size of the MCMC variability within the interpretation software STRmix™ compared to other sources of variability in forensic DNA profiling including PCR, capillary electrophoresis load and injection, and the makeup of allele frequency databases. The MCMC variability within STRmix™ was shown to be the smallest source of variability in this process.

A forensic perspective on the genetic identification of grapevine (Vitis vinifera L.) varieties using STR markers.

The grapevine (Vitis vinifera subsp. vinifera) is one of the most important agricultural crops worldwide. A long interest in the historical origins of ancient and cultivated current grapevines, as well as the need to establish phylogenetic relationships and parentage, solve homonymies and synonymies, fingerprint cultivars and clones, and assess the authenticity of plants and wines has encouraged the development of genetic identification methods. STR analysis is currently the most commonly used method for these purposes. A large dataset of grapevines genotypes for many cultivars worldwide has been produced in the last decade using a common set of recommended dinucleotide nuclear STRs. This type of marker has been replaced by long core-repeat loci in standardized state-of-the-art human forensic genotyping. The first steps toward harmonized grapevine genotyping have already been taken to bring the genetic identification methods closer to human forensic STR standards by previous authors. In this context, we bring forward a set of basic suggestions that reinforce the need to (i) guarantee trueness-to-type of the sample; (ii) use the long core-repeat markers; (iii) verify the specificity and amplification consistency of PCR primers; (iv) sequence frequent alleles and use these standardized allele ladders; (v) consider mutation rates when evaluating results of STR-based parentage and pedigree analysis; (vi) genotype large and representative samples in order to obtain allele frequency databases; (vii) standardize genotype data by establishing allele nomenclature based on repeat number to facilitate information exchange and data compilation.

CYP2C9 polymorphism analysis in Han Chinese populations: building the largest allele frequency database

Genetic polymorphisms of CYP2C9 significantly influence the pharmacokinetics and pharmacodynamics of some drugs, which might result in adverse drug effects and therapeutic failure. Several studies have been performed on CYP2C9 genetic polymorphisms in Han Chinese populations. However, these studies only focused on two commonly investigated alleles, *2 and *3, in relatively small sample sizes. To scale up the gene-scanning region and determine relatively precise data on the genetic distribution pattern in Chinese populations, unrelated healthy Han Chinese volunteers from Zhejiang Province (n=1127) and Hebei (n=1000) Province were recruited as subjects for the direct sequencing of all exons of CYP2C9. As a result, 14 previously reported alleles were detected in this work, and 8 of these alleles (*14, *16, *19, *23, *27, *29, *33 and *34) were described for the first time in Chinese populations. In addition, 37 novel mutations were also detected, of which 22 variants were non-synonymous, and 21 new alleles, *36-*56, were designated by the Human CYP Allele Nomenclature Committee. In vitro functional analysis of these 22 novel CYP2C9 variants revealed that 17 mutations had a significant influence on the protein's catalytic activity. Our study provides the most accurate data on CYP2C9 polymorphisms in Han Chinese populations and detects the largest number of novel allelic variants existing to date. These new alleles will greatly enrich the current knowledge of naturally occurring CYP2C9 variants in Chinese populations.

Introducing the Forensic Research/Reference on Genetics knowledge base, FROG-kb.

BackgroundOnline tools and databases based on multi-allelic short tandem repeat polymorphisms (STRPs) are actively used in forensic teaching, research, and investigations. The Fst value of each CODIS marker tends to be low across the populations of the world and most populations typically have all the common STRP alleles present diminishing the ability of these systems to discriminate ethnicity. Recently, considerable research is being conducted on single nucleotide polymorphisms (SNPs) to be considered for human identification and description. However, online tools and databases that can be used for forensic research and investigation are limited.MethodsThe back end DBMS (Database Management System) for FROG-kb is Oracle version 10. The front end is implemented with specific code using technologies such as Java, Java Servlet, JSP, JQuery, and GoogleCharts.ResultsWe present an open access web application, FROG-kb (Forensic Research/Reference on Genetics-knowledge base, http://frog.med.yale.edu), that is useful for teaching and research relevant to forensics and can serve as a tool facilitating forensic practice. The underlying data for FROG-kb are provided by the already extensively used and referenced ALlele FREquency Database, ALFRED (http://alfred.med.yale.edu). In addition to displaying data in an organized manner, computational tools that use the underlying allele frequencies with user-provided data are implemented in FROG-kb. These tools are organized by the different published SNP/marker panels available. This web tool currently has implemented general functions possible for two types of SNP panels, individual identification and ancestry inference, and a prediction function specific to a phenotype informative panel for eye color.ConclusionThe current online version of FROG-kb already provides new and useful functionality. We expect FROG-kb to grow and expand in capabilities and welcome input from the forensic community in identifying datasets and functionalities that will be most helpful and useful. Thus, the structure and functionality of FROG-kb will be revised in an ongoing process of improvement. This paper describes the state as of early June 2012.

European Network of Forensic Science Institutes (ENFSI): Evaluation of new commercial STR multiplexes that include the European Standard Set (ESS) of markers

To support and to underpin the European initiative to increase the European set of standard markers (ESS), by the addition of five new loci, a collaborative project was organised by the European Network of Forensic Science Institutes (ENFSI) DNA working group in order to assess the new multiplex kits available. We have prepared allele frequency databases from 26 EU populations. Concordance studies were carried out to verify that genotyping results were consistent between kits. Population genetics studies were conducted and it was estimated that FST<0.001. The results showed that the kits were comparable to each other in terms of performance and major discrepancy issues were highlighted. We provide details of allele frequencies for each of the populations analysed per laboratory.