Bypassing Mendel’s First Law: Transmission Ratio Distortion in Mammals

G. Friocourt, A. Perrin, P. A. Saunders, E. Nikalayevich, C. Voisset, C. Coutton, G. Martinez and F. Morel,  International Journal Molecular Sciences,  24. 2023.

 The different biological mechanisms inducing a transmission ratio distortion ranging from gamete formation to lethality at post-natal stages.

Mendel’s law of segregation states that the two alleles at a diploid locus should be transmitted equally to the progeny. A genetic segregation distortion, also referred to as transmission ratio distortion (TRD), is a statistically significant deviation from this rule. TRD has been observed in several mammal species and may be due to different biological mechanisms occurring at diverse time points ranging from gamete formation to lethality at post-natal stages. In this review, we describe examples of TRD and their possible mechanisms in mammals based on current knowledge. We first focus on the differences between TRD in male and female gametogenesis in the house mouse, in which some of the most well studied TRD systems have been characterized. We then describe known TRD in other mammals, with a special focus on the farmed species and in the peculiar common shrew species. Finally, we discuss TRD in human diseases. Thus far, to our knowledge, this is the first time that such description is proposed. This review will help better comprehend the processes involved in TRD. A better understanding of these molecular mechanisms will imply a better comprehension of their impact on fertility and on genome evolution. In turn, this should allow for better genetic counseling and lead to better care for human families.

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