Table 2 Genetic polymorphisms in the canid TRNP1 gene, variant allele frequencies (AF) and predicted effect of variants on regulatory and coding regionsÂ
Gene region | Genetic polymorphism | Variant AF D W C | Predicted effect | Known function or expression of affected transcription factor or miRNA in brain tissue |
|---|---|---|---|---|
Promoter | c.-702 C > G | 0.00 0.03 0.00 | TCF3, NFIC binding site deleted | Both genes expressed in cerebral cortex. TCF3 is a transcriptional regulator involved in the initiation of neuronal differentiation and mesenchymal to epithelial transition |
|  | c.-665 C > T | 0.00 0.00 0.10 | KLF4 binding site deleted; New NR2E3 binding site | KLF4 regulates the expression of key transcription factors during embryonic development. NR2E3 involved in cerebellar cortex morphogenesis |
|  | c.-607 T > C | 0.00 0.00 0.05 | None |  |
|  | c.-584 G > A | 0.00 0.00 0.10 | New CTCF binding site | Negative regulation of cell population proliferation |
|  | c.-444 C > A | 0.00 0.00 0.05 | MYC binding site deleted; New TBXT, ZEB1 binding sites; Increased binding for EN1 | MYC expressed in the proliferating cells of the developing CNS. EN1 and TBXT involved in cerebellar cortex and neural plate morphogenesis. ZEB1 positively regulates neuronal differentiation. |
|  | c.-412 C > T | 0.60 0.15 0.00 | New ZFX binding site | None reported |
|  | c.-355 C > T | 0.00 0.00 0.05 | New PAX5, PAX6 binding sites; Increased binding for RUNX1 | PAX important for cerebellar cortex morphogenesis, including regulation of neuroblast proliferation and neuron migration. RUNX1 involved in neuron differentiation. |
|  | c.-256 G > C | 0.00 0.03 0.00 | ELK1, MIZF binding sites deleted | ELK1 Is a positive regulator of neuron death while MIZF is involved in cerebellar cortex morphogenesis. |
| Â | c.-240delA | 0.76 0.38 0.05 | REST, ZNF423 binding sites deleted | Expressed in neural progenitor cells, REST is a transcriptional repressor that regulates neurogenesis and neuron differentiation. ZNF423 regulates cerebellar granule cell precursor cell proliferation. |
|  | c.-161 T > G | 0.04 0.10 0.10 | SpI1 binding site deleted; Increased binding for NFYA | None reported |
5’UTR | c.-129 A > G | 0.13 0.08 0.10 | New binding sites for TBP | None reported |
|  | c.-104 T > C | 0.00 0.03 0.00 | None predicted |  |
|  | c.-79 C > T | 0.00 0.00 0.10 | New binding sites for ARNT and CREB1 | CREB1 involved in axonogenesis |
|  | c.-58 C > T | 0.25 0.15 0.00 | None predicted |  |
Coding | c.134 C > A | 0.00 0.00 0.05 | p.(Pro45Gln) – probably damaging |  |
|  | c.141 T > G | 0.39 1.00 0.85 | p.Pro47= |  |
|  | c.232 A > T | 0.00 0.43 0.25 | p.(Thr78Ser) – probably benign |  |
|  | c.259_264 delGCGGCG | 0.00 0.48 0.35 | p.(Ala87_Ala88del) – may alter spacer length |  |
|  | c.453 G > A | 0.00 0.03 0.00 | Gln151Gln |  |
3’UTR | c.*19 A > G | 0.00 0.05 0.00 | None |  |
|  | c.*41 G > T | 0.08 0.13 0.00 | None |  |
|  | c.*149 C > T | 0.00 0.00 0.05 | None |  |
|  | c.*257 G > A | 0.00 0.00 0.15 | New sites for hsa-miR-335-3p, 450b-3p, 769-3p, 5694 | hsa-miR-335, 769 expressed at high levels in human brain |
|  | c.*280 C > A | 0.03 0.00 0.00 | None |  |
|  | c.*286 A > G | 0.13 0.23 0.00 | None |  |
| Â | c.*370_371insTG | 0.64 0.95 1.00 | Deletion of hsa-miR-128, 216a, 3681 sites | cfa-miR-128-1 detected in canine cerebrospinal fluid; hsa-miR-128-3p, 216a-3p expressed at high levels in human brain |
|  | c.*452 T > A | 0.00 0.00 0.05 | None |  |
|  | c.*454 A > G | 0.00 0.00 0.05 | None |  |
|  | c.*482 C > T | 0.01 0.28 0.05 | Deletion of hsa-miR-549a-3p site |  |
|  | c.*495 C > G | 0.03 0.00 0.55 | Deletion of hsa-miR-6820-3p, hsa-miR-3164 sites |  |