CLINICAL EXAMPLE: INVERSIONS (Page 25)

; [What happens when a TAD boundary is deleted at the LMNB1 locus?]

Deletion of a TAD boundary causes TAD fusion and enhancer adoption – the relocation of enhancer elements into a neighbouring TAD causes misexpression and disease.

; [How does enhancer adoption work in this example?]

Through the deletion of the boundary, the enhancer of gene B is free to act on gene A, driving ectopic expression in the developing limbs.

; [What disease is associated with LMNB1 TAD boundary deletion?]

Adult-onset demyelinating leukodystrophy.

; [What happens with inter-TAD inversions?]

An inter-TAD inversion of an enhancer element can cause enhancer adoption, causing ectopic expression of gene A in the limbs. At the same time, the inversion removes the enhancer element from gene B, resulting in regulatory loss of function in the limbs.  ; [What clinical condition is associated with inversions at the EPHA4 locus?]