Assessing the effects of subpopulations on the application of forensic DNA profiling.

Doctoral thesis English OPEN
Clark, Dan

Currently, UK forensic service providers (FSPs) tend to employ three geographically-broad databases when estimating profile frequencies based on a standard SGM Plus® DNA profile. These estimations will typically include correction factors to take into account issues such as substructuring of populations and sampling inefficiencies. It has been shown previously that regional genetic variation within the UK ‘Caucasian’ population is negligible but consideration has to be made for profiles which may originate from an individual of a more genetically isolated population.\ud \ud Samples were collected from Indian, Pakistani and UK (white British) donors; as well as Kalash individuals, a small population from the Khyber Pakhtunkhwa region in the North West of Pakistan. These were profiled using the SGM Plus® and Identifiler® kits and databases for each population were compiled.\ud \ud The greatest pairwise FST was seen between the Kalash and Indian population at 2.9 %. Allele frequency data were collected for each population and each sample’s profile frequency was estimated against all other databases to see whether samples reported a more conservative profile frequency (higher match probability) in their cognate database or in that of another population. A combined database comprising the Indian, Pakistani and previously published Bangladeshi data was also formed and used to calculate the level of correction required to make all samples of a population report a more conservative profile frequency in this combined database as opposed to their cognates. At the standard FST correction of 3 % – the minimum correction used by some FSPs, 94 % of the UK samples reported a more conservative profile frequency in the South Asian database; the lowest proportion that did so from all four populations. The Kalash dataset required the highest correction factor at FST = 12 % to make 100 % of samples report more conservative match probabilities when measured against the combined database.\ud \ud It was established that the current levels of correction applied to profile frequency calculations were more than sufficient; with random match probabilities remaining in the order of less than one in one billion for all samples in all databases with a correction of FST = 5 %. Although significant pairwise FST differences were observed as well as significant differentiation between populations across all SGM Plus® loci, no evidence of substructuring was detected using a program which employs a Bayesian probabilistic clustering approach, STRUCTURE, likely due to an insufficient number of samples and number of loci tested. \ud \ud Marked differences were seen in allele frequencies of the Kalash population, which also exhibited the highest affiliation to their cognate database, at least 80 %, with or without correction. AMOVA analysis also confirmed the greatest variance between groups was seen when the Kalash were kept as a separate entity from the other South Asian populations.\ud \ud Although current UK practice for applying FST correction prior to estimating STR match probabilities seems generous, there will be occasions when an estimation may appear less conservative when based on a broad database. Conversely, in this study, the one in one billion match probability ceiling threshold was not exceeded for any sample being compared to all databases. Therefore, although consideration should be given to a suspect’s reference population prior to frequency estimation, the current correction factors applied should be sufficient in the vast majority of cases. In instances where partial profiles are obtained, this caused little effect on the estimation of geographic origin, compared to full profiles, with the populations used in this study.
  • References (62)
    62 references, page 1 of 7

    Bauchet, M., McEvoy, B., Pearson, L. N., Quillen, E. E., Sarkisian, T., Hovhannesyan, K., Deka, R., Bradley, D. G., & Shriver, M. D., (2007) 'Measuring European population stratification with Microarray Genotype Data'. Am. J. Hum. Genet., 80, (5), p.948-956 Baye, T. M., Tiwari, H. K., Allison, D. B., & Go, R. C. (2009) 'Database mining for selection of SNP markers useful in admixture mapping'. BioData Min., 2, (1). p.1-8 Behar, D. M., Villems, R., Soodyall, H., Blue-Smith, J., Pereira, L., Metspalu, E., Scozzari, R., Makkan, H., Tzur, S., Comas, D., Bertranpetit, J., Quintana-Murci, L., Tyler-Smith, C., Spencer Wells, R., & Rosset, S., (2008) 'The Dawn of Human Matrilineal Diversity'. Am. J. Hum. Genet., 82, (5), p.1130-1140

    Bender, K., Schneider, P. M., & Rittner, C. (2000) 'Application of mtDNA sequence analysis in forensic casework for the identification of human remains'. Forensic Sci. Int., 113, (1-3), p.103-107

    Bhopal, R. & Donaldson, L. (1998) 'White, European, Western, Caucasian, or what? Inappropriate labelling in research on race, ethnicity, and health'. Am. J. Public Health, 88, p.1303-1307

    Binda, S., Borer, U. V., Gehrig, C., Hochmeister, M., & Budowle, B. (2000) 'Swiss Caucasian population data for the STR loci D2S1338 and D19S433 using the AmpFℓSTR SGM plus PCR amplification kit'. Forensic Sci. Int., 108, (2), p.117-120 Botstein, D., White, R. L., Skolnick, M., & Davis, R. W. (1980) 'Construction of a genetic linkage map in man using restriction fragment length polymorphisms'. Am. J. Hum. Genet., 32, (3), p.314-331

    Bowcock, A. M., Ruiz-Linares, A., Tomfohrde, J., Minch, E., Kidd, J. R., & CavalliSforza, L. L. (1994) 'High resolution of human evolutionary trees with polymorphic microsatellites'. Nature, 368, (6470), p.455-457

    Brenner, C. H. (1998) 'Difficulties in the estimation of ethnic affiliation'. Am. J. Hum. Genet., 62, (6), p.1558-1560

    Briggs, A. W., Good, J. M., Green, R. E., Krause, J., Maricic, T., Stenzel, U., LaluezaFox, C., Rudan, P., Brajković, D., Kućan, Ž., Gušic, I., Schmitz, R., Doronichev, V. B., Golovanova, L. V., de la Rasilla, M., Fortea, J., Rosas, A., & Pääbo, S., (2009) 'Targeted retrieval and analysis of five Neandertal mtDNA genomes'. Science, 325, p.318-321

    Brinkmann, B., Klintschar, M., Neuhuber, F., Hühne, J., & Rolf, B., (1998) 'Mutation Rate in Human Microsatellites: Influence of the Structure and Length of the Tandem Repeat'. Am. J. Hum. Genet., 62, p.1408-1415

    Buckleton, J. S., Curran, J. M., & Walsh, S. J. (2006) 'How reliable is the subpopulation model in DNA testimony?' Forensic Sci. Int., 157, p.144-148 Budowle, B., Allard, M. W., Wilson, M. R., & Chakraborty, R. (2003) 'Forensics and Mitochondrial DNA: Applications, Debates, and Foundations'. Annu. Rev. Genomics Hum. Genet. 4, p.119-141

    Budowle, B., Wilson, M. R., DiZinno, J. A., Stauffer, C., Fasano, M. A., Holland, M. M., & Monson, K. L. (1999) 'Mitochondrial DNA regions HVSI and HVSII population data'. Forensic Sci. Int., 103, (1), p.23-35

  • Related Research Results (1)
  • Similar Research Results (1)
  • Metrics
    views in OpenAIRE
    views in local repository
    downloads in local repository

    The information is available from the following content providers:

    From Number Of Views Number Of Downloads
    Central Lancashire Online Knowledge - IRUS-UK 0 196
Share - Bookmark