Figure 5. The TAD boundary at the FMR1 daSTR is ablated in Fragile X Syndrome (FXS).

(A) 5C contact matrices in B-lymphocytes from a male with FXS with a full mutation of ~935 CGG repeats (Coriell Catalog ID GM09237), a healthy male sibling (GM09236), and a genetically unrelated male with FXS and with a full mutation of ~645 CGG repeats in length (GM04025). (B-C) Zoomed-in 5C heatmaps on the FMR1 locus are shown for the B-lymphocytes from an FXS patient and healthy sibling. The log fold change between the diseased and healthy sibling 5C highlights contacts gained (red) and depleted (blue). Green arrows point to loops lost in disease and green brackets annotate the region of increased interaction frequency indicative of boundary disruption. (D) Zoomed-in 5C heatmaps on the FMR1 locus for an additional genetically unrelated patient (645 repeats, Coriell Catalog ID GM04025), and fold change map compared to sample GM09236. (E) 5C contact matrices in human cerebellum tissue from an unaffected individual (Control 1, age of death 62) and from an individual with FXS (Case 1, age of death 60). The FMR1 gene is highlighted in green and the repeat demarcated by a red vertical line. (F) Zoomed-in 5C heatmaps on the FMR1 locus for the brain samples shown in (B). (G-H) A metric quantifying boundary strength, directionality index, is plotted at the FMR1 daSTR boundary (B1) and a boundary distal from FMR1 (B2) for affected and unaffected patient samples. See also Figure S7.