Top

Published in:

01-05-2016 | Original Article

Mixtures with relatives and linked markers

Authors: Guro Dørum, Daniel Kling, Andreas Tillmar, Magnus Dehli Vigeland, Thore Egeland

Published in: International Journal of Legal Medicine | Issue 3/2016

Abstract

Mixture DNA profiles commonly appear in forensic genetics, and a large number of statistical methods and software are available for such cases. However, most of the literature concerns mixtures where the contributors are assumed unrelated and the genetic markers are unlinked. In this paper, we consider mixtures of linked markers and related contributors. If no relationships are involved, linkage can be ignored. While unlinked markers can be treated independently, linkage introduces dependencies. The use of linked markers presents statistical and computational challenges, but may also lead to a considerable increase in power since the number of markers available is much larger if we do not require the markers to be unlinked. In addition, some cases that cannot be solved with an unlimited number of unlinked autosomal markers can be solved with linked markers. We focus on two special cases of linked markers: pairs of linked autosomal markers and X-chromosomal markers. A framework is presented for calculation of likelihood ratios for mixtures with general relationships and with linkage between any number of markers. Finally, we explore the effect of linkage disequilibrium, also called allelic association, on the likelihood ratio.

Abecasis G, Cherny S, Cookson W, Cardon L (2002) Merlin-rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet 30:97–101CrossRefPubMed

Boyles A, Scott W, Martin E, Schmidt S, Li Y, Ashley-Koch A, Bass M, Schmidt M, Pericak-Vance M, Speer M, Hauser E (2005) Linkage disequilibrium inflates type I error rates in multipoint linkage analysis when parental genotypes are missing. Hum Hered 59(4):220–227. doi:10.1159/000087122 CrossRefPubMedPubMedCentral

Bright J-A, Curran JM, Buckleton JS (2013) Relatedness calculations for linked loci incorporating subpopulation effects. Forensic Sci Int: Genet 7(3):380–383. doi:10.1016/j.fsigen.2013.03.002 CrossRef

Buckleton J, Triggs C, Walsh S (eds) (2005) Forensic DNA evidence interpretation. CRC Press

Curran J, Triggs C, Buckleton J, Weir B (1999) Interpreting DNA mixtures in structured populations. J Forensic Sci 44(5):987– 995CrossRefPubMed

Daniel R, Santos C, Phillips C, Fondevila M, van Oorschot R, Carracedo Á., Lareu M, McNevin D (2015) A SNaPshot of next generation sequencing for forensic SNP analysis. Forensic Sci Int: Genet 14(0):50–60CrossRef

Dawid A, Mortera J, Pascali VL (2001) Non-fatherhood or mutation?: a probabilistic approach to parental exclusion in paternity testing. Forensic Sci Int 124(1):55–61. doi:10.1016/S0379-0738(01)00564-3 CrossRefPubMed

Egeland T, Sheehan N (2008) On identification problems requiring linked autosomal markers. Forensic Sci Int: Genet 2(3):219–225. doi:10.1016/j.fsigen.2008.02.006 CrossRef

Egeland T, Dørum G, Vigeland MD, Sheehan NA (2014) Mixtures with relatives: a pedigree perspective. Forensic Sci Int: Genet 10:49–54. doi:10.1016/j.fsigen.2014.01.007 CrossRef

10.

Fung WK, Hu YQ (2004) Interpreting DNA mixtures with related contributors in subdivided populations. Scand J Stat 31(1):115–130. doi:10.1111/j.1467-9469.2004.00376.x CrossRef

11.

Fung WK, Hu YQ (2008) Statistical DNA Forensics: Theory, methods and computation. Wiley, England

12.

Hu YQ, Fung W (2005) Evaluation of DNA mixtures involving two pairs of relatives. Int J Legal Med 119 (5):251–259. doi:10.1007/s00414-004-0493-9 CrossRefPubMed

13.

Huang Q, Shete S, Amos C (2004) Ignoring linkage disequilibrium among tightly linked markers induces false-positive evidence of linkage for affected sib pair analysis. Am J Human Genet 75(6):1106–1112. doi:10.1086/426000 CrossRef

14.

Kling D, Tillmar A, Egeland T, Mostad P (2014) A general model for likelihood computations of genetic marker data accounting for linkage, linkage disequilibrium, and mutations. International Journal of Legal Medicine, pp 1–12. doi:10.1007/s00414-014-1117-7

15.

Kling D, Dell’Amico B, Tillmar AO (2015) Famlinkx—implementation of a general model for likelihood computations for x-chromosomal marker data. Forensic Sci Int: Genet 17:1–7. doi:10.1016/j.fsigen.2015.02.007 CrossRef

16.

Kong A, Thorleifsson G, Gudbjartsson DF, Masson G, Sigurdsson A, Jonasdottir A, Walters GB, Jonasdottir A, Gylfason A, Kristinsson KT, Gudjonsson SA, Frigge ML, Helgason A, Thorsteinsdottir U, Stefansson K (2010) Fine-scale recombination rate differences between sexes, populations and individuals. Nature 467(7319):1099–1103. doi:10.1038/nature09525 CrossRefPubMed

17.

Kruijver M (2015) Efficient computations with the likelihood ratio distribution. Forensic Sci Int: Genet 14:116–124. doi:10.1016/j.fsigen.2014.09.018 CrossRef

18.

Lancia M, Severini S, Coletti A, Margiotta G, Dobosz M, Carnevali E (2011) Using x-chromosomal markers in rape investigation. Forensic Sci Int: Genet Suppl Ser 3(1):e55 – e56. doi:10.1016/j.fsigss.2011.08.027

19.

Mayor LR, Balding DJ (2006) Discrimination of half-siblings when maternal genotypes are known. Forensic Sci Int 159:141–147. doi:10.1016/j.forsciint.2005.07.007 CrossRefPubMed

20.

Nothnagel M, Szibor R, Vollrath O, Augustin C, Edelmann J, Geppert M, Alves C, Gusmao L, Vennemann M, Hou Y, Immel U-D, Inturri S, Luo H, Lutz-Bonengel S, Robino C, Roewer L, Rolf B, Sanft J, Shin K-J, Sim JE, Wiegand P, Winkler C, Krawczak M, Hering S (2012) Collaborative genetic mapping of 12 forensic short tandem repeat (STR) loci on the human X chromosome. Forensic Sci Int: Genet 6(6):778–784. doi:10.1016/j.fsigen.2012.02.015 CrossRef

21.

O’Connor KL, Tillmar AO (2012) Effect of linkage between vWA and D12s391 in kinship analysis. Forensic Sci Int: Genet 6(6):840–844. doi:10.1016/j.fsigen.2012.03.008 CrossRef

22.

Phillips C, Fernandez-Formoso L, Garcia-Magariños M, Porras L, Tvedebrink T, Amigo J, Fondevila M, Gomez-Tato A, Alvarez-Dios J, Freire-Aradas A, Gomez-Carballa A, Mosquera-Miguel A, Carracedo Á, Lareu M (2011) Analysis of global variability in 15 established and 5 new european standard set (ESS) STRs using the CEPH human genome diversity panel. Forensic Sci Int: Genet 5(3):155–169. doi:10.1016/j.fsigen.2010.02.003 CrossRef

23.

Skare O, Sheehan N, Egeland T (2009) Identification of distant family relationships. Bioinformatics 25 (18):2376–2382. doi:10.1093/bioinformatics/btp418 CrossRefPubMed

24.

Slooten K-J, Egeland T (2015) Exclusion probabilities and likelihood ratios with applications to mixtures. Int J Legal Med:1–19. doi:10.1007/s00414-015-1217-z

25.

Szibor R (2007) X-chromosomal markers: Past, present and future. Forensic Sci Int: Genet 1(2, SI):93–99. doi:10.1016/j.fsigen.2007.03.003 CrossRef

26.

Szibor R, Krawczak M, Hering S, Edelmann J, Kuhlisch E, Krause D (2003) Use of x-linked markers for forensic purposes. Int J Legal Med 117(2):67–74. doi:10.1007/s00414-002-0352-5 CrossRefPubMed

27.

Thompson E (1986) Pedigree analysis in human genetics. The Johns Hopkins University Press, Baltimore

28.

Thompson EA (1975) The estimation of pairwise relationships. Ann Human Genet 39(2):173–88CrossRef

29.

Thompson EA (2000) Statistical Inference from Genetic Data on Pedigrees, volume 6 of NSF-CBMS Regional Conference Series in Probability and Statistics. IMS, Beachwood, Ohio

30.

Thompson EA, Meagher TR (1998) Genetic linkage in the estimation of pairwise relationship. Theor Appl Genet 97(5-6):857–864. doi:10.1007/s001220050965 CrossRef

31.

Tillmar AO (2012) Population genetic analysis of 12 X-STRs in Swedish population. Forensic Sci Int: Genet 6(2):e80 – e81. doi:10.1016/j.fsigen.2011.07.008 CrossRef

32.

Tillmar AO, Mostad P (2014) Choosing supplementary markers in forensic casework. Forensic Sci Int: Genet 13(0):128–133. doi:10.1016/j.fsigen.2014.06.019 CrossRef

33.

Tillmar AO, Mostad P, Egeland T, Lindblom B, Holmlund G, Montelius K (2008) Analysis of linkage and linkage disequilibrium for eight X-STR markers. Forensic Sci Int: Genet 3(1):37–41. doi:10.1016/j.fsigen.2008.09.006 CrossRef

34.

Tillmar AO, Egeland T, Lindblom B, Holmlund G, Mostad P (2011) Using X-chromosomal markers in relationship testing: Calculation of likelihood ratios taking both linkage and linkage disequilibrium into account. Forensic Sci Int: Genet 5(5):506–511. doi:10.1016/j.fsigen.2010.11.004 CrossRef

Title: Mixtures with relatives and linked markers
Authors: Guro Dørum
Daniel Kling
Andreas Tillmar
Magnus Dehli Vigeland
Thore Egeland
Publication date: 01-05-2016
Publisher: Springer Berlin Heidelberg
Published in: International Journal of Legal Medicine / Issue 3/2016
Print ISSN: 0937-9827
Electronic ISSN: 1437-1596
DOI: https://doi.org/10.1007/s00414-015-1288-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Mixtures with relatives and linked markers

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2016

Fatal right coronary artery rupture following blunt chest trauma: detection by postmortem selective coronary angiography

Radiologic assessment of third molar tooth and spheno-occipital synchondrosis for age estimation: a multiple regression analysis study

3D documentation and visualization of external injury findings by integration of simple photography in CT/MRI data sets (IprojeCT)

Searching for biological traces on different materials using a forensic light source and infrared photography

The rate of RNA degradation in human dental pulp reveals post-mortem interval

Enlarged parietal foramina: a rare forensic autopsy finding