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Analysis of parental-origin effects in linkage data

Molecular Psychiatry volume 5, pages 125–126 (2000)Cite this article

SIR – Hall postulated that one explanation for a non-Mendelian inheritance pattern in complex diseases is due to the presence of susceptibility loci which demonstrate parental-origin effects, or genomic imprinting.1 There has been considerable interest in the differential behavior of alleles based on parental sex in bipolar affective disorder on chromosome 18.2, 3, 4 However, potential complexities result from the classification of families into ‘parental’, ‘maternal’ and ‘other’ where in fact such ‘parental’ pedigrees are defined as having either an affected father, or sib or parent of the father affected. Gershon3 acknowledged that the classification of a particular pedigree can be rather arbitrary and makes the unstated assumption of intra-familial locus homogeneity—all affected individuals within each pedigree are due to the same locus. Thus, analysis of ‘paternal‘ and ‘maternal’ pedigrees separately may not be entirely appropriate. Pairwise parametric linkage analysis with separate estimation of recombination distances in paternal and maternal chromosomes has been suggested as a way to demonstrate imprinting5—this is, in fact, recommended as routine for all linkage analysis.6

Similarly, affected sibpair analysis performed after families have been divided into ‘paternal’ and ‘maternal’ has weaknesses, since it does not take into account whether the shared alleles are inherited from the affected, unaffected, or both parents. Stine et al2 faced this problem in their chromosome 18 study—in pedigrees with ‘paternal’ bipolar or recurrent unipolar disorder there was excess sharing of maternal alleles, but not paternal alleles at D18S464. A similar discordant finding arose in a recent study using a parametric approach;4 the most significant pairwise result from the whole study is at D18S453 in ‘paternal’ families using a recessive model (lod = 1.91 at θ = 0.0), while with a dominant model the evidence for linkage was lower (lod 0.47, θ = 0.1). The evidence for linkage at this marker in these ‘paternal’ families is strongest using a recessive model, suggesting that disease alleles have to be inherited from both the mother and father.

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References

  1. Hall JG . Am J Hum Genet 1990; 46: 857–873

  2. Stine OC et al. Am J Hum Genet 1995; 57: 1384–1394

  3. Gershon ES et al. Am J Med Genet 1996; 67: 202–207

  4. Nöthen MM et al. Mol Psychiatry 1999; 4: 76–84

  5. Smalley SL . Am J Hum Genet 1993; 52: 210–212

  6. Terwilliger JD, Ott J . Handbook of Human Genetic Linkage John Hopkins University Press, Baltimore 1994; pp 139–148

    Google Scholar 

  7. Broman KW et al. Am J Hum Genet 1998; 63: 861–869

  8. Hinds DA, Risch N ftp://lahmed.stanford.edu/pub/aspex/

  9. Van Broeckhoven C, Verheyen G . Psychiatr Genet 1998; 8: 97–108

  10. Popper K . Open Society vol 2: Routledge, London 1963; p 363

    Google Scholar 

  11. Halpern J, Whittemore AS . Hum Hered 1999; 49: 194–196

    Article  CAS  Google Scholar 

  12. Daw EW et al. Am J Hum Genet 1998; 63S: 85

Download references

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  1. Clarke Division, Department of Psychiatry, Neurogenetics Section, Centre for Addiction and Mental Health, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8, Canada

    A D Paterson

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  1. A D Paterson
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Paterson, A. Analysis of parental-origin effects in linkage data. Mol Psychiatry 5, 125–126 (2000). https://doi.org/10.1038/sj.mp.4000667

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