Discriminating between allele‐ and genotype‐specific transmission ratio distortion

Abstract

Transmission ratio distortion (TRD) is defined as the observed deviation from the expected Mendelian inheritance of alleles from heterozygous parents. This phenomenon is attributed to various biological mechanisms acting on germ cells, embryos or fetuses, or even in early postnatal life. Current statistical approaches typically use two independent parametrizations assuming that TRD relies on allele-or genotype-related mechanisms, although they have never been tested and compared. This study compared allele-and genotype-related TRD models on simulated datasets with 1000 genotyped offspring and real data from 168 sire-dam-offspring beef cattle trios. The analysis of simulated datasets favored the true model of analysis in most cases (>93%), and a low percentage of missidentification occurred under (almost) null dominance (genotype-related model) or similar and moderate-to-low sire-and dam-specific TRD parameters (allele-related model). Moreover, the correlation between simulated and predicted distortion parameters was high (>0.97) under the true model. The comparison of allele-and genotype-related TRD models is an appealing tool to infer the biological source of TRD (i.e. haploid vs. diploid cells) when screening the whole genome. The analysis of beef cattle data corroborated a TRD region previously reported in chromosome 4, although discarding allele-related mechanisms and favoring the genotyperelated model as the more reliable one. The results of this study highlight the relevance of implementing and comparing different parametrizations to capture all kinds of TRD, and to compare them using appropriate statistical methods.

Deviations from Mendelian Inheritance on Bovine X-Chromosome Revealing Recombination, Sex-of-Offspring Effects and Fertility-Related Candidate Genes

“…As introduced previously, similar patterns of TRD on only one sex (specific sex-offspring TRD) were already identified in the human X-chromosome using microsatellite loci [ 16 ]. In fact, related patterns were also described for some disease (e.g., retinoblastoma) and were hypothesized to be associated with defective imprinting [ 34 ]. In addition, the sire-TRD pattern could be due to the fact that DNA sequences remain methylated for a much longer period in the male germline than in the female germline [ 35 ].…”

Discovering lethal alleles across the turkey genome using a transmission ratio distortion approach

“…As described by Casellas et al . (2012, In press), the probability of observing offspring ( p off ) from heterozygous‐by‐heterozygous mating can be estimated as follows:where α g j and δ g j are additive and dominance TRD parameters for the specific allele j respectively.…”

“…These two parametrizations have been already evaluated in a previous study (Casellas et al . In press) reporting the relevance of implementing and comparing the different parametrizations to capture all types of TRD. The objective of this study was to assess TRD based on allelic and genotypic parameterizations and perform a functional gene set enrichment analysis to uncover biological pathways associated with TRD in a purebred line of turkeys.…”

Unravelling the genetics of non-random fertilization associated with gametic incompatibility

“…in mice 10 and plants 11 ), but to our knowledge, no studies have explored genetic incompatibility in livestock species. To study possible gametic incompatibility, the TRD model from Casellas et al 12 , 13 was adapted by including a gametic interaction term in addition to the direct TRD effect, which is based on the parental allele transmission differential.…”