The other possibility is that the variant may act at the level of the messenger RNA.
Importantly, our preliminary findings also suggest that the CD44v3 variant may act to limit endocrine response in the clinic.
We cannot, however, exclude that the variant may act as a modifying or low penetrance gene that may exhibit incomplete segregation and retention of the wild-type allele, as has been demonstrated for the CHEK2 gene [ 9, 10].
The amount of total CHK2 protein, and phosphorylation of CHK2 on Thr68, in heterozygous LCLs was reduced to about half compared to wild-type LCLs, suggesting that 1100delC variant may act simply by haploinsufficiency.
Considering the diverse and temporarily restricted roles of Dazl in germ cell development and oocyte-to-zygote transition [ 34, 35], it is tempting to speculate that the maternal and zygotic isoforms may be responsible for two biological processes: the 'maternal' version may act in the oocyte-to-zygote transition, whereas the zygotic variant may act in germ cell development.
This information is important, as the investigation of other established disease variants in genomic regions associated with endometriosis can aid in revealing the potentially biological mechanisms through which the variant may act upon endometriosis pathogenesis, and can lead to new investigations of joint aetiology and co-morbidity.
However, it is important to assess the possibility that the variant may act directly through the specific DNA change (e.g. through splicing disruption as assessed through at least computational analysis) instead of through the amino acid change, in which case the assumption of pathogenicity may no longer be valid.
Further RNAfold prediction analysis showed a MFE changed from −182.5 kcal/mol to −126.0 kcal/mol, when the nucleotide at the pri-miR-218 rs11134527 locus changed from A to G, indicating that this variant may act as a functional SNP, which affects the miRNA binding process and contributes to cervical cancer susceptibility.
Each PARK2 splice variants may acts in different manner to suit cell specific needs.
