Table 1.
Use of genome-editing techniques to examine functionality of noncoding variants
| Genome-editing Tool | Trait | Locus | Lead SNPs | Investigated SNP | Functionality Demonstrated through Genome-editing | Reference |
|---|---|---|---|---|---|---|
| Zinc-finger nuclease | breast cancer | FGFR2 | rs2981578 rs1219648 rs2981582 rs2981579 | rs2981578 | effects on cell proliferation, cell cycle progression, and transcription factor binding examined, showing no allele-specific effects | (43) |
| TALEN | prostate cancer | RFX6 | rs339331 | rs339331 | prostate cancer cell lines homozygous for risk alleles demonstrated increased RFX6 gene expression and increased HOXB13 transcription factor occupancy | (44) |
| CRISPR-Cas9 | Type 2 diabetes | TCF7L2 | rs7903146 | rs7903146 | allele-specific effects demonstrated in a human colorectal carcinoma cell line on ACSL5 gene expression and long-range chromatin contacts | (31) |
| Type 2 diabetes | PPARG2 | n/a | rs4684847 | preadipocytes with nonrisk allele introduced showed increased PPARG2 transcript levels, mediated by PRRX1 transcription factor | (32) | |
| lipids | CPNE1 | rs2277862 | rs2277862 | allele-specific effects on gene CPNE1 gene expression observed upon differentiation of hPSCs into adipocytes | (39) | |
| coronary artery disease | PHACTR1 | rs9349379 | rs9349379 | deletion surrounding rs9349379 resulted in decrease of PHCTR1 gene expression | (40) | |
| obesity | IRX3/IRX5 | rs1558902 | rs1421085 | allele-specific gene expression observed upon adipocyte differentiation in presence of the repressor, ARID5B | (41) | |
| renal cancer | MYC/PVT1 | rs35252396 | rs35252396 | mutations introduced to an HIF-binding site surrounding rs35252396 led to reduction in MYC and PVT1 gene expression | (46) | |
| Parkinson's disease | SNCA | rs356220 rs356219 rs356182 | rs356168 | iPSCs differentiated into neuronal precursors showed higher levels of SNCA gene expression for carriers of the risk allele | (47) | |
| ankylosing spondylitis | PTGER4 | n/a | rs9283753 | using lymphoblast cell lines, allele-specific effects on PTGER4 gene expression were observed | (48) |
CRISPR-Cas9, clustered regularly interspaced short palindromic repeats with Cas9 nuclease; iPSC, induced pluripotent stem cell; SNP, single-nucleotide polymorphism; TALEN, transcription activator-like effector nucleases.