Figure 1.

Schematic representation of the FSHD locus, ORFs, transcripts and location of miRNA-sized fragments. The top panel shows the FSHD locus with two full D4Z4 units. The region centromeric to the D4Z4 units is designated as p13E-11. The small triangle represents a partial D4Z4 unit centromeric to the First and Last D4Z4 units (large triangles), followed by another partial D4Z4 unit (partial triangle), then the region designated as pLAM, followed by beta-satellite repeat sequence. The sequence in Supplementary Material, Figure S1 extends from the first D4Z4 unit through the pLAM sequence and is numbered 0 to 7760, as shown schematically. First repeat ORFs: schematic of ORFs in the first D4Z4 unit that extends from position 0 to 3300. Each ORF is predicted from the DNA sequence and denoted by the first few amino acids. MKG, MAL and MQG represent internal in-frame methionines that might also be used for translation initiation. The ORF beginning with MAL is the previously identified DUX4 ORF. STOP indicates a stop-codon in-frame with the upstream ORF. Numbering is from the KPNI site at the beginning of the D4Z4 repeat to the KPNI site at the end of the repeat. Last repeat ORFs: potential ORFs in the last D4Z4 unit differ from first due to sequence variations. Transcripts mapped by strand-specific RT–PCR and small RNAs: map of transcription units determined by strand-specific RT–PCR in wild-type and FSHD fibroblasts and muscle cells. Solid arrows (A–F) represent regions where strand-specific RT–PCR has identified RNA transcripts and dashed lines represent regions where transcripts were not identified. Location of the endpoints of these transcripts in the first/last repeats is as follows: A, 404/3701-1325/4628; B, 1614/4912-2237/5535; C, 2704/6002-3340/6638; D, 1003-1374/4672; E, 1623/4921-2100/5400; F, 2634/5932-3071/6369. Asterisks represent locations of small miRNA-sized fragments confirmed by northern.