The common deletion in PWS spans about 4 Mbp on the proximal long arm of chromosome 15 (for a review, see also Ref. ). The imprinted region consists in about 2 Mbp within the commonly deleted region. One gene in the region, UBE3A, functions only with its maternally derived allele in the brain, and its deficit leads to AS (see Angelman Syndrome). A UBE3A mutation alone can produce the whole AS phenotype. On the other hand, there are at least five genes that are expressed only by their paternal alleles. Thus, in PWS the relative contributions of different gene deficiencies for the phenotype is unclear. Among the imprinted genes that are deficient in PWS one important candidate for a major phenotype contributor is SNURF-SNRPN, which is a very complex, polycistronic gene coding for two independent proteins. One of them, the protein SmN, translates off exons 4-10, and is a core spliceosomal protein that participates in the process of mRNA splicing in the brain. The five reported balanced translocations (see Type lib PWS) that resulted in PWS had their breakpoint within the SNURF-SNRPN locus, thus suggesting the gene's major role in the PWS phenotype. However, mouse models with altered SNURF-SNRPN sequence do not seem to show the PWS-like phenotype. SmN's function in the brain overlaps with the SmB/B proteins. The SmB/B proteins have elevated levels in the mouse model with an ablated SmN sequence, thus supporting the idea that the SmB/B proteins can compensate for the SmN deficiency in the mouse model. SNRPN upstream reading frame (SNURF) (exons 1-3) encodes another protein that may be involved in the regulation of SmN or in the process of imprinting because its locus overlaps with the IC. In addition, there are genes for many small nucleolar RNAs located within the SNURF-SNRPN introns. The impaired transcription of these RNA molecules may also be an important contributor for the PWS phenotype.
Finally, another major candidate contributor for the PWS phenotype is the gene NDN whose products are predominantly expressed in the brain.
Was this article helpful?
The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.