International Journal of Legal Medicine

, Volume 132, Issue 2, pp 361–371 | Cite as

Curiosities of X chromosomal markers and haplotypes

Original Article


Recent progress in forensic genetics has introduced a number of closely located short tandem repeat (STR) markers on the X chromosome. Inevitably, dependencies arise that have to be accounted for. This paper will in detail explore the complex statistical interpretation of X-chromosomal STR markers, focusing on likelihood calculations. Specifically, we will investigate how the phase uncertainty of haplotypes comes into play in the statistical evaluations and what curious effects this phenomenon can have. The starting point is the different real cases where the weight of evidence has provided unexpected results that require further investigation in order to be fully understood. We will touch upon subjects such as association between alleles, recombinations, and mutations. The aim of this study is to facilitate a better understanding of the interaction between the concepts in addition to provide an understanding why good estimates of haplotype frequencies are crucial. The individual subjects have been discussed in other fields, whereas this study will focus on forensic applications where few studies have been conducted relating to the understanding of how these concepts interact.


X STR Argus X12 Haplotypes LD Mutations 

Supplementary material

414_2017_1612_MOESM1_ESM.doc (148 kb)
ESM 1 (DOC 148 kb)


  1. 1.
    Edelmann J et al (2001) 16 X-chromosome STR loci frequency data from a German population. Forensic Sci Int 124(2/3):215–218Google Scholar
  2. 2.
    Edelmann J et al (2012) X-chromosomal haplotype frequencies of four linkage groups using the Investigator Argus X-12 Kit. Forensic Sci Int: Genet 6(1):e24–e34CrossRefGoogle Scholar
  3. 3.
    Bini C et al (2015) Expanding X-chromosomal forensic haplotype frequencies database: Italian population data of four linkage groups. Forensic Sci Int: Genet 15:127–130CrossRefGoogle Scholar
  4. 4.
    Chen MY, Ho CW, Pu CE, Wu FC (2014) Genetic polymorphisms of 12 X-chromosomal STR loci in Taiwanese individuals and likelihood ratio calculations applied to case studies of blood relationships. Electrophoresis 35(12–13):1912–1920Google Scholar
  5. 5.
    Cainé LM et al (2010) Genetic data of a Brazilian population sample (Santa Catarina) using an X-STR decaplex. J Forensic Legal Med 17(5):272–274CrossRefGoogle Scholar
  6. 6.
    Zarrabeitia MT et al (2009) Analysis of 10 X-linked tetranucleotide markers in mixed and isolated populations. Forensic Sci Int: Genet 3(2):63–66CrossRefGoogle Scholar
  7. 7.
    Kling D et al (2014) Population genetic analysis of 12 X-STRs in a Somali population sample. Forensic Sci Int: Genet 11:e7–e8CrossRefGoogle Scholar
  8. 8.
    Tillmar AO (2012) Population genetic analysis of 12 X-STRs in Swedish population. Forensic Sci Int: Genet 6(2):e80–e81CrossRefGoogle Scholar
  9. 9.
    Hedman M, Palo J, Sajantila A (2009) X-STR diversity patterns in the Finnish and the Somali population. Forensic Sci Int: Genet 3(3):173–178CrossRefGoogle Scholar
  10. 10.
    Poulsen L et al (2016) NGMSElect™ and Investigator® Argus X-12 analysis in population samples from Albania, Iraq, Lithuania, Slovenia, and Turkey. Forensic Sci Int: Genet 22:110–112CrossRefGoogle Scholar
  11. 11.
    Shi M et al (2005) Genetic polymorphisms of four STR loci on chromosome X and their forensic applications in a Chinese Han population. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 22(3):268–271PubMedGoogle Scholar
  12. 12.
    Tomas C, Pereira V, Morling N (2012) Analysis of 12 X-STRs in Greenlanders, Danes and Somalis using Argus X-12. Int J Legal Med 126(1):121–128CrossRefPubMedGoogle Scholar
  13. 13.
    Turrina S et al (2007) Development and forensic validation of a new multiplex PCR assay with 12 X-chromosomal short tandem repeats. Forensic Sci Int: Genet 1(2):201–204CrossRefGoogle Scholar
  14. 14.
    Zidkova A, Capek P, Horinek A, Coufalova P (2014) Investigator® Argus X-12 study on the population of Czech Republic: comparison of linked and unlinked X-STRs for kinship analysis. Electrophoresis 35(14):1989–1992Google Scholar
  15. 15.
    Gusmão L et al (2009) A GEP-ISFG collaborative study on the optimization of an X-STR decaplex: data on 15 Iberian and Latin American populations. Int J Legal Med 123(3):227–234CrossRefPubMedGoogle Scholar
  16. 16.
    Diegoli TM et al (2011) Allele frequency distribution of twelve X-chromosomal short tandem repeat markers in four US population groups. Forensic Sci Int: Genet Suppl Ser 3(1):e481–e483Google Scholar
  17. 17.
    Pinto N, Gusmao L, Amorim A (2011) X-chromosome markers in kinship testing: a generalisation of the IBD approach identifying situations where their contribution is crucial. Forensic Sci Int: Genet 5(1):27–32CrossRefGoogle Scholar
  18. 18.
    Pinto N, Silva PV, Amorim A (2012) A general method to assess the utility of the X-chromosomal markers in kinship testing. Forensic Sci Int: Genet 6(2):198–207CrossRefGoogle Scholar
  19. 19.
    Nothnagel M et al (2012) Collaborative genetic mapping of 12 forensic short tandem repeat (STR) loci on the human X chromosome. Forensic Sci Int: Genet 6(6):778–784CrossRefGoogle Scholar
  20. 20.
    Szibor R (2007) X-chromosomal markers: past, present and future. Forensic Sci Int: Genet 1(2):93–99CrossRefGoogle Scholar
  21. 21.
    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 17:1–7CrossRefGoogle Scholar
  22. 22.
    Tillmar AO et al (2010) 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):506–511CrossRefGoogle Scholar
  23. 23.
    Diegoli TM (2015) Forensic typing of short tandem repeat markers on the X and Y chromosomes. Forensic Sci Int: Genet 18:140–151CrossRefGoogle Scholar
  24. 24.
    Slatkin M (2008) Linkage disequilibrium—understanding the evolutionary past and mapping the medical future. Nat Rev Genet 9(6):477–485CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Stephens M, Smith NJ, Donnelly P (2001) A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 68(4):978–989CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Gao G, Allison DB, Hoeschele I (2009) Haplotyping methods for pedigrees. Hum Hered 67(4):248–266CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Iliadis A et al (2010) A haplotype inference algorithm for trios based on deterministic sampling. BMC Genet 11:78CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Kling D., et al. (2014) A general model for likelihood computations of genetic marker data accounting for linkage, linkage disequilibrium, and mutations. Int J Legal Med 1–12Google Scholar
  29. 29.
    Ellegren H (2004) Microsatellites: simple sequences with complex evolution. Nat Rev Genet 5(6):435–445CrossRefPubMedGoogle Scholar
  30. 30.
    Ellegren H (2000) Heterogeneous mutation processes in human microsatellite DNA sequences. Nat Genet 24(4):400–402CrossRefPubMedGoogle Scholar
  31. 31.
    Egeland T, Kling D, Mostad P (2015) Relationship inference with familias and R: statistical methods in forensic genetics. Academic PressGoogle Scholar
  32. 32.
    Conrad DF et al (2006) A worldwide survey of haplotype variation and linkage disequilibrium in the human genome. Nat Genet 38(11):1251–1260CrossRefPubMedGoogle Scholar
  33. 33.
    Reich DE et al (2001) Linkage disequilibrium in the human genome. Nature 411(6834):199–204CrossRefPubMedGoogle Scholar
  34. 34.
    Dawid AP, Mortera J, Pascali VL (2001) Non-fatherhood or mutation?: a probabilistic approach to parental exclusion in paternity testing. Forensic Sci Int 124(1):55–61CrossRefPubMedGoogle Scholar
  35. 35.
    Ricciardi F, Slooten K (2014) Mutation models for DVI analysis. Forensic Sci Int: Genet 11:85–95Google Scholar
  36. 36.
    Valdes AM, Slatkin M, Freimer N (1993) Allele frequencies at microsatellite loci: the stepwise mutation model revisited. Genetics 133(3):737–749PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Department of Forensic ServicesOslo University HospitalOsloNorway

Personalised recommendations