What inheritance pattern increases the likelihood of expansion in trinucleotide repeat disorders (TRDs)?

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The inheritance pattern that increases the likelihood of expansion in trinucleotide repeat disorders (TRDs) is paternal inheritance. In several disorders that are characterized by trinucleotide repeat expansions, such as Huntington's disease and Fragile X syndrome, it has been observed that expansions are more commonly transmitted through the male line.

This phenomenon is due to several factors related to gametogenesis. During spermatogenesis, the process of sperm development involves numerous cellular divisions and is subject to different biological mechanisms compared to oogenesis, the process of egg development. In particular, the unstable repeats can undergo further expansions during the replication of DNA in male germ cells, leading to an increased number of repeats being passed on to the offspring.

As a result, when the disorder is inherited paternally, there is a greater risk for the next generation to receive an expanded version of the repeat, which can contribute to an earlier onset and more severe form of the disease compared to maternal inheritance, where such expansions are less frequent. Hence, paternal inheritance is the correct answer as it directly relates to the increased risk of these expansions occurring in certain TRDs.

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