Transmission Ratio Distortion: A Neglected Phenomenon with Many Consequences in Genetic Analysis and Population Genetics

  • Aurélie Labbe
  • Lam Opal Huang
  • Claire Infante-Rivard


Transmission ratio distortion (TRD) is defined as a statistical departure from the Mendelian 1:1 inheritance ratio and occurs when one of the two alleles from either parent is preferentially transmitted to the offspring (Pardo-Manuel de Villena and Sapienza 2001). This phenomenon is conventionally assessed by the transmission disequilibrium test (TDT) (Spielman et al. 1993), which measures the departure from the expected transmission of an allele from heterozygous parents to affected offspring. In such cases, a departure from Mendelian ratios suggests the presence of linkage and association between the allele and the offspring condition. The TDT and other family-based tests of transmission for linkage disequilibrium and association have been used extensively as one way to provide validation for case–control results while controlling for population structure bias. However, TRD has also been empirically observed in offspring unselected for disease (Infante-Rivard and Weinberg 2005; Naumova et al. 1998; Paterson et al. 2003, 2009; Zollner et al. 2004), which suggests the occurrence of the TRD phenomena in apparently unaffected populations. Although its extent in the human genome is not yet well known, it has also been extensively identified in other species such as mice (LeMaire-Adkins and Hunt 2000; Lyon 2003; Wu et al. 2005), drosophila (Novitski 1951; Sturtevant 1936; Zimmering 1955), and lesser kestrel (Aparicio et al. 2010). Many of the reported TRD loci play a role in tumor suppression and have been found in colon cancer, leukemia, bladder cancer, intestinal adenoma, node-positive breast cancer, and other cancers (De Rango et al. 2007; Eaves et al. 1999; Naumova et al. 2001; Paterson et al. 2009). A number of TRD loci are within gene regions responsible for imprinting (Eversley et al. 2010; Naumova et al. 2001; Yang et al. 2008), such as D12Nds2 on chromosome 12 and H19 on 11p15.5, leading to loss of imprint and embryonic lethality. Many TRD loci have also been linked to abnormal development in neurogenesis, neuronal differentiation, and other cognitive functions in the central and peripheral nervous system (De Rango et al. 2007; Eversley et al. 2010; Naumova et al. 2001; Paterson et al. 2009; Paterson and Petronis 1999; Riess et al. 1997).


Recombination Fraction Transmission Disequilibrium Test Mendelian Ratio Meiotic Drive Transmission Ratio Distortion 
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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Aurélie Labbe
    • 1
    • 2
  • Lam Opal Huang
    • 1
  • Claire Infante-Rivard
    • 1
  1. 1.Department of Epidemiology, Biostatistics and Occupational HealthMcGill UniversityMontréalCanada
  2. 2.Douglas Mental Health University InstituteMontrealCanada

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