This locus had the largest effect on maturity-induced senescence in a previous study [ 24], and in the current study, also had the strongest effect on mean percent mortality in both single locus and pair-wise loci analyses.
This is consistent with a previous study that reported LD in eight breeds of cattle [ 17] and showed that the LD between pair-wise loci drops to background LD level at a distance of 500 kb.
The calculation of association for pair-wise loci as outlined by the two-locus genetic model of Risch (2000) was performed for the polymorphism at the NQO1 and TP53 gene loci, since these were the only two polymorphic sites that showed a significant association if the two studies were combined.
Lastly, no signs of linkage disequilibrium were apparent for any of the 15 pair-wise locus combinations (P≥0.1).
Since we had analysed eight different SNPs in six different genes, we also investigated for the presence of linkage disequilibrium and for pair-wise locus association.
For both IHR1s and IHR2s with CpG islands, the pair-wise genomic loci of HCEs are only significantly sparse in the "intronic-intronic" class [see Additional file 18; Hypergeometric test, p value = 0.0024], which can easily be understood that there are exonic sequences residing in between the HCEs and that promoter elements (i.e. CpG islands) are less likely to be located in the exonic regions.
Differential methylation analysis aims to determine methylation differences between the specific groups (such as cases and controls), such as probe-wise or locus-specific methylation differences; the two terminologies are therefore equivalent when at the individual locus level.
Indeed, for all isolates, 33 of 36 pair wise combinations of loci displayed significant linkage (p-value<0.0014), compared to 11/36 for SM and 4/36 for MM, respectively.
Furthermore, the study presents evidence for inter- and intragenic pair-wise interaction between loci in genes of both families (NRG1-NRG2, NRG2-EGFR, NRG1-NRG3 and ERBB4-ERBB4).
When a locus wise DNA sequences data in each case was compared, it showed electromorphic size variation solely attributed either due to expansion/contraction of the SSRs, or due to interruptions in the SSR regions.
Specifically, we do not know if they are 'weaponized' by the step-wise acquisition of virulence loci, or if pathogens transition from one pathogroup to another by multi-locus emergence.
