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

Abstract

Deviation from Mendelian inheritance expectations (transmission ratio distortion, TRD) has been observed in several species, including the mouse and humans. In this study, TRD was characterized in the turkey genome using both allelic (specific- and unspecific-parent TRD) and genotypic (additive- and dominance-TRD) parameterizations within a Bayesian framework. In this study, we evaluated TRD for 23 243 genotyped Turkeys across 56 393 autosomal SNPs. The analyses included 500 sires, 2013 dams and 11 047 offspring (trios). Three different haplotype sliding windows of 4, 10 and 20 SNPs were used across the autosomal chromosomes. Based on the genotypic parameterizations, 14 haplotypes showed additive and dominance TRD effects highlighting regions with a recessive TRD pattern. In contrast, the allelic model uncovered 12 haplotype alleles with the allelic TRD pattern which showed an underrepresentation of heterozygous offspring in addition to the absence of homozygous animals. For regions with the allelic pattern, only one particular region showed a parent-specific TRD where the penetrance was high via the dam, but low via the sire. The gene set analysis uncovered several gene ontology functional terms, Reactome pathways and several Medical Subject Headings that showed significant enrichment of genes associated with TRD. Many of these gene ontology functional terms (e.g. mitotic spindle assembly checkpoint, DRM complex and Aneuploidy), Reactome pathways (e.g. Mismatch repair) and Medical Subject Headings (e.g. Adenosine monophosphate) are known to be related to fertility, embryo development and lethality. The results of this study revealed potential novel candidate lethal haplotypes, functional terms and pathways that may enhance breeding programs in Turkeys through reducing mortality and improving reproduction rate.

Keywords: fertility; functional analysis; gene set enrichment; lethal haplotypes; transmission ratio distortion.

Figure 1

Bayes factor for haplotypes with transmission ratio distortion across the turkey genome. Significant haplotype alleles were determined based on log₁₀ Bayes factor ≥2 according to Jeffreys’ scale (Jeffreys 1984)

Figure 2

Venn diagram showing overlaps between significant genes associated with the terms of three GO domains (presented in Tables 3, 4, 5) and the Reactome pathways (presented in Table 6)

Figure 3

Network integration of gene MAD1L1 based on physical protein interaction and co‐expression. The gene APITD1 is associated with MAD1L1 through pathways (links are not shown)

Figure 4

Network integration of gene LIG1 based on physical protein interaction and co‐expression. The gene UBE2R2 is associated with LIG1 through prediction (links are not shown)