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Human Genetics

, Volume 132, Issue 3, pp 245–263 | Cite as

Transmission ratio distortion: review of concept and implications for genetic association studies

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

Abstract

Transmission ratio distortion (TRD) occurs when one of the two alleles from either parent is preferentially transmitted to the offspring. This leads to a statistical departure from the Mendelian law of inheritance, which states that each of the two parental alleles is transmitted to offspring with a probability of 0.5. A number of mechanisms are thought to induce TRD such as meiotic drive, gametic competition, and embryo lethality. TRD has been extensively studied in animals, but the prevalence of TRD in humans remains largely unknown. Nevertheless, understanding the TRD phenomenon and taking it into consideration in many aspects of human genetics has potential benefits that have not been sufficiently emphasized in the current literature. In this review, we discuss the importance of TRD in three distinct but related fields of genetics: developmental genetics which studies the genetic abnormalities in zygotic and embryonic development, statistical genetics/genetic epidemiology which utilizes population study designs and statistical models to interpret the role of genes in human health, and population genetics which is concerned with genetic diversity in populations in an evolutionary context. From the perspective of developmental genetics, studying TRD leads to the identification of the processes and mechanisms for differential survival observed in embryos. As a result, it is a genetic force which affects allele frequency at the population, as well as, at the organismal level. Therefore, it has implications on genetic diversity of the population over time. From the perspective of genetic epidemiology, the TRD influence on a marker locus is a confounding factor which has to be adequately dealt with to correctly interpret linkage or association study results. These aspects are developed in this review. In addition to these theoretical notions, a brief summary of the empirical evidence of the TRD phenomenon in human and mouse studies is provided. The objective of our paper is to show the potentially important role of TRD in many areas of genetics, and to create an incentive for future research.

Keywords

Spinal Muscular Atrophy Transmission Disequilibrium Test Meiotic Drive Transmission Ratio Distortion Marker Allele Frequency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

The study complies with the current laws of Canada.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

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

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