Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Survival Motor Neuron 1 (SMN1) is a causative gene for autosomal recessive infantile and juvenile proximal spinal muscular atrophy. SMN1 duplications have recently been found to increase susceptibility to amyotrophic lateral sclerosis. The role of centromeric SMN copy (SMN2) has been postulated in progressive muscular atrophy (PMA). The aim of this study was to analyse the SMN1 and SMN2 copy number variations in patients with PMA. SMN1 and SMN2 genotype was studied in 87 patients with PMA, diagnosed at the Department of Neurology, Medical University of Warsaw, between 1992 and 2012 and in 600 healthy controls. Results demonstrated that three copies of SMN1 were found in 8.1% of PMA patients and in 24% of PMA patients with disease duration above 48 months compared to 4.6% of the general population. Patients with three SMN1 copies had a limb onset, lower median age of onset and longer disease duration compared to patients with two SMN1 copies. There were no significant differences in the SMN2 copy numbers. In conclusion, the increased copy number of SMN1 may be a susceptibility factor to PMA and influence the clinical phenotype.
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PMID:SMN1 gene duplications are more frequent in patients with progressive muscular atrophy. 2347 10

Telomerase and telomeric complex have been linked to a variety of disease states related to neurological dysfunction. In amyotrophic lateral sclerosis (ALS) patients, telomerase activity, as human telomerase reverse transcriptase (hTERT) expression, has not been characterized yet. Here, for the first time, we characterized telomerase and related pathway in blood sample and spinal cord from ALS patients compared with healthy controls. We found that hTERT expression level was significantly lower in ALS patients and was correlated either to p53 mRNA expression or p21 expression, pointing out the hypothesis that telomerase inhibition could be a pathogenetic contributor to neurodegeneration in ALS. As a consequence of the reduced telomerase activity, we identified shorter telomeres in leukocytes from sporadic ALS patients compared with healthy control group.
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PMID:Telomerase expression in amyotrophic lateral sclerosis (ALS) patients. 2514 9

The common bean (Phaseolus vulgaris L.) is the world's most important legume for human consumption. Anthracnose (ANT; Colletotrichum lindemuthianum) and angular leaf spot (ALS; Pseudocercospora griseola) are complex diseases that cause major yield losses in common bean. Depending on the cultivar and environmental conditions, anthracnose and angular leaf spot infections can reduce crop yield drastically. This study aimed to estimate linkage disequilibrium levels and identify quantitative resistance loci (QRL) controlling resistance to both ANT and ALS diseases of 180 accessions of common bean using genome-wide association analysis. A randomized complete block design with four replicates was performed for the ANT and ALS experiments, with four plants per genotype in each replicate. Association mapping analyses were performed for ANT and ALS using a mixed linear model approach implemented in TASSEL. A total of 17 and 11 significant statistically associations involving SSRs were detected for ANT and ALS resistance loci, respectively. Using SNPs, 21 and 17 significant statistically associations were obtained for ANT and angular ALS, respectively, providing more associations with this marker. The SSR-IAC167 and PvM95 markers, both located on chromosome Pv03, and the SNP scaffold00021_89379, were associated with both diseases. The other markers were distributed across the entire common bean genome, with chromosomes Pv03 and Pv08 showing the greatest number of loci associated with ANT resistance. The chromosome Pv04 was the most saturated one, with six markers associated with ALS resistance. The telomeric region of this chromosome showed four markers located between approximately 2.5 Mb and 4.4 Mb. Our results demonstrate the great potential of genome-wide association studies to identify QRLs related to ANT and ALS in common bean. The results indicate a quantitative and complex inheritance pattern for both diseases in common bean. Our findings will contribute to more effective screening of elite germplasm to find resistance alleles for marker-assisted selection in breeding programs.
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PMID:Genome-Wide Association Studies of Anthracnose and Angular Leaf Spot Resistance in Common Bean (Phaseolus vulgaris L.). 2693 78

Non-Saccharomyces species have been recognized for their beneficial contribution to fermented food and beverages based on their volatile compound formation and their ability to ferment glucose into ethanol. At the end of fermentation brewer's yeast flocculate which provides an easy means of separation of yeasts from green beer. Flocculation in Saccharomyces cerevisiae requires a set of flocculation genes. These FLO-genes, FLO1, FLO5, FLO9, FLO10, and FLO11, are located at telomeres and transcription of these adhesins is regulated by Flo8 and Mss11. Here, we show that Saccharomycopsis fermentans, an ascomycete yeast distantly related to S. cerevisiae, possesses a very large FLO/ALS-like Sequence (FAS) family encompassing 34 genes. Fas proteins are variable in size and divergent in sequence and show similarity to the Flo1/5/9 family. Fas proteins show the general build with a signal peptide, an N-terminal carbohydrate binding PA14 domain, a central region differing by the number of repeats and a C-terminus with a consensus sequence for GPI-anchor attachment. Like FLO genes in S. cerevisiae, FAS genes are mostly telomeric with several paralogs at each telomere. We term such genes that share evolutionary conserved telomere localization "telologs" and provide several other examples. Adhesin expression in S. cerevisiae and filamentation in Candida albicans is regulated by Flo8 and Mss11. In Saccharomycopsis we identified only a single protein with similarity to Flo8 based on sequence similarity and the presence of a LisH domain.
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PMID:Expansion of a Telomeric FLO/ALS-Like Sequence Gene Family in Saccharomycopsis fermentans. 3054 68

Telomere loops (t-loops) are formed at the ends of chromosomes in species ranging from humans to worms, plants, and with genetic manipulation, some yeast. Recent in vitro studies demonstrated that transcription of telomeric DNA leads to highly efficient t-loop formation. It was also shown that both DNA termini are inserted into the preceding DNA to generate a highly stable t-loop junction. Furthermore, some telomeric RNA remains present at the junction, potentially acting as a plug to further protect and stabilize the t-loop. Modeling the loop junction reveals two mechanisms by which the canonical chromosomal replication factors could extend the telomere in the absence of telomerase. One mechanism would utilize the annealed 3' terminus as a de novo replication origin. In vitro evidence for the ability of the t-loop to prime telomere extension using the T7 replication factors is presented. A second mechanism would involve resolution of the Holliday junction present in the t-loop bubble by factors such as GEN1 to generate a rolling circle template at the extreme terminus of the telomere. This could lead to large expansions of the telomeric tract. Here, we propose that telomeres evolved as terminal elements containing long arrays of short nucleotide repeats due to the ability of such arrays to fold back into loops and self-prime their replicative extension. In this view, telomerase may have evolved later to provide a more precise mechanism of telomere maintenance. Both pathways have direct relevance to the alternative lengthening of telomeres (ALT) pathway. This view also provides a possible mechanism for the very large repeat expansions observed in nucleotide repeat diseases such as Fragile X syndrome, myotonic dystrophy, familial amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). The evolution of telomeres is discussed in the framework of these models.
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PMID:A New View of the T-Loop Junction: Implications for Self-Primed Telomere Extension, Expansion of Disease-Related Nucleotide Repeat Blocks, and Telomere Evolution. 3147 42


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