Genetic and expression studies of SMN2 gene in Russian patients with spinal muscular atrophy type II and III

<p>Abstract</p> <p>Background</p> <p>Spinal muscular atrophy (SMA type I, II and III) is an autosomal recessive neuromuscular disorder caused by mutations in the survival motor neuron gene (<it>SMN1</it>). <it>SMN2 </it>is a centromeric copy gene that has been characterized as a major modifier of SMA severity. SMA type I patients have one or two <it>SMN2 </it>copies while most SMA type II patients carry three <it>SMN2 </it>copies and SMA III patients have three or four <it>SMN2 </it>copies. The <it>SMN1 </it>gene produces a full-length transcript (FL-SMN) while <it>SMN2 </it>is only able to produce a small portion of the FL-SMN because of a splice mutation which results in the production of abnormal SMNΔ7 mRNA.</p> <p>Methods</p> <p>In this study we performed quantification of the <it>SMN2 </it>gene copy number in Russian patients affected by SMA type II and III (42 and 19 patients, respectively) by means of real-time PCR. Moreover, we present two families consisting of asymptomatic carriers of a homozygous absence of the <it>SMN1 </it>gene. We also developed a novel RT-qPCR-based assay to determine the FL-SMN/SMNΔ7 mRNA ratio as SMA biomarker.</p> <p>Results</p> <p>Comparison of the <it>SMN2 </it>copy number and clinical features revealed a significant correlation between mild clinical phenotype (SMA type III) and presence of four copies of the <it>SMN2 </it>gene. In both asymptomatic cases we found an increased number of <it>SMN2 </it>copies in the healthy carriers and a biallelic <it>SMN1 </it>absence. Furthermore, the novel assay revealed a difference between SMA patients and healthy controls.</p> <p>Conclusions</p> <p>We suggest that the <it>SMN2 </it>gene copy quantification in SMA patients could be used as a prognostic tool for discrimination between the SMA type II and SMA type III diagnoses, whereas the FL-SMN/SMNΔ7 mRNA ratio could be a useful biomarker for detecting changes during SMA pharmacotherapy.</p

Growth rate and heterozygosity in the plaice, Pleuronectes platessa

Samples of young plaice were examined to see if there was any relationship between growth rate and individual heterozygosity, screened across five polymorphic enzyme loci (Pgm-1, Ada, Mdh-2, Pgi-2, Gpdh-l). Two out of 46 samples showed a significant negative correlation between growth rate and multi-locus heterozygosity; none showed a significant positive correlation. There was no overall tendency to negative or positive correlations. The largest sample (N=689) showed no relationship between multi-locus heterozygosity and growth rate, although one of the five loci, Gpdh-1, showed a significant positive correlation. The only significant correlation in the next largest sample (N= 248) was between multi-locus heterozygosity and growth rate, and that was negative. Fish of intermediate growth rate were not significantly different in heterozygosity from faster or slower growing fish. There was no relationship between variability in growth rate and multi-locus heterozygosity. These findings are discussed in the context of similar surveys from other species, and the conclusion drawn that the universality of a positive relationship between growth rate and multi-locus heterozygosity remains to be established

University Students’ Sense of Belonging to the Home Town: The Role of Residential Mobility

Place identity, Sense of community, University students,