Fig. 2

Chromosome 4q35.2 in healthy- and in FSHD1-individuals. 11–150 D4Z4 repeats (dark blue) leading to a high methylation level within the D4Z4 macrosatellite (light blue), which represses the transcription of DUX4. There are two possible haplotypes A and B, which are equally common and a Simple Sequence Length Polymorphism (SSLP) proximal to the D4Z4 repeat further classifying haplotype A or B [36]. FSHD only occurs in individuals, which carry the 4qA allele. People with contraction and thus minor methylation at chromosome 4q35 are either also carrying 4qA and have FSHD or 4qB and are healthy. The 4qA haplotype is further classified based on SSLPs proximal to the D4Z4 repeat. Only the common SSLP variant 4A161 and the rare variants 4A159 and 4A168 are reported to correlate with D4Z4 reduced alleles in FSHD patients. This example: 1–10 repeats/ FSHD1; the same conditions of a permissive Haplotype A apply for FSHD2 [36]. Haplotype A further carries the pLAM1 sequence (light green) and a beta-satellite repeat region immediately distal to the D4Z4 repeat (yellow). Detection is depicted via Southern Blot probe p13E-11 (dark green). Chromosome 10q26 is also illustrated as it shows nearly 100% similarity to the 4q35 locus [36]