Table 2.
TADs and TBRs of Genes with Historically Well-Known Long-Range cis-Regulation Associated with a Phenotype
| Locus (Chromosome Band) | TAD and TBR Nucleotides (hESC, GRCh37/hg19)18(Size) | Genetic Alterations | Phenotype |
|---|---|---|---|
|
PAX6-WT1 (11p23) |
TBR: 30,963,424–31,083,424 (120 kb), TAD: 31,083,424–32,323,424 (1.24 Mb), TAD: 32,323,424–32,643,424 (320 kb), TBR: 32,643,424–32,683,424 (40 kb), |
disruption of regulatory elements up to 150 kb downstream of PAX6 | aniridia21 |
| deletions involving PAX6 and WT1, which includes the TBR between the TADs of these genes | WAGR syndrome22 | ||
| haploinsufficiency of WT1 | syndromes involving genitourinary anomalies without aniridia23 | ||
|
TWIST1 (7p21.1) |
TAD: 18,713,475–19,153,475 (440 kb), TAD: 19,153,475–19,713,475 (560 kb) |
disruption of regulatory elements up to 260 kb downstream of TWIST1 | Saethre-Chotzen syndrome24 |
|
SOX9 (17q24.3) |
TAD: 68,648,405–70,528,405 (1.88 Mb) | disruption of regulatory elements up to 1.5 Mb upstream of SOX9 | Pierre Robin sequence25 |
|
SHH (7q36.3) |
TAD: 155,587,239–157,187,239 (1.6 Mb) | disruption of regulatory elements up to 265 kb upstream of SHH | HPE326 |
| disruption of regulatory elements up to 1 Mb upstream of SHH | preaxial polydactyly26 | ||
|
POU3F4 (Xq21.1) |
TAD: 80,073,344–83,113,344 (3.04 Mb) | disruption of regulatory elements up to 900 kb upstream of POU3F4 | X-linked deafness27 |
Abbreviations are as follows: hESC, human embryonic stem cell; HPE3, holoprosencephaly type 3; TAD, topologically associated domain; TBR, topological boundary region; and WAGR, Wilms tumor, aniridia, genitourinary anomalies, and mental retardation.