Sulfotransferase 1A3/4 copy number variation is associated with neurodegenerative disease

Butcher, Neville J.; Horne, Malcolm; Mellick, George D.; Fowler, Christopher; Masters, Colin L.; Minchin, Rodney F.

doi:10.1038/tpj.2017.4

Cited by 23 publications

(18 citation statements)

References 53 publications

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“…SULT1A3 is a protein-coding gene related to sulfotransferase enzymes that catalyze the sulfate conjugation of many hormones and neurotransmitters. It has been found that Alzheimer's subjects have a significant lower SULTA13 copy number compared to healthy controls [24]. Induction of SULTA13 significantly protects cells from dopamine neurotoxicity.…”

Section: Vs Healthy Controls Classificationmentioning

confidence: 99%

Robust Sampling of Defective Pathways in Alzheimer’s Disease. Implications in Drug Repositioning

Fernández-Martínez

Álvarez-Machancoses

Andrés-Galiana

et al. 2020

IJMS

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We present the analysis of the defective genetic pathways of the Late-Onset Alzheimer’s Disease (LOAD) compared to the Mild Cognitive Impairment (MCI) and Healthy Controls (HC) using different sampling methodologies. These algorithms sample the uncertainty space that is intrinsic to any kind of highly underdetermined phenotype prediction problem, by looking for the minimum-scale signatures (header genes) corresponding to different random holdouts. The biological pathways can be identified performing posterior analysis of these signatures established via cross-validation holdouts and plugging the set of most frequently sampled genes into different ontological platforms. That way, the effect of helper genes, whose presence might be due to the high degree of under determinacy of these experiments and data noise, is reduced. Our results suggest that common pathways for Alzheimer’s disease and MCI are mainly related to viral mRNA translation, influenza viral RNA transcription and replication, gene expression, mitochondrial translation, and metabolism, with these results being highly consistent regardless of the comparative methods. The cross-validated predictive accuracies achieved for the LOAD and MCI discriminations were 84% and 81.5%, respectively. The difference between LOAD and MCI could not be clearly established (74% accuracy). The most discriminatory genes of the LOAD-MCI discrimination are associated with proteasome mediated degradation and G-protein signaling. Based on these findings we have also performed drug repositioning using Dr. Insight package, proposing the following different typologies of drugs: isoquinoline alkaloids, antitumor antibiotics, phosphoinositide 3-kinase PI3K, autophagy inhibitors, antagonists of the muscarinic acetylcholine receptor and histone deacetylase inhibitors. We believe that the potential clinical relevance of these findings should be further investigated and confirmed with other independent studies.

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Section: Vs Healthy Controls Classificationmentioning

confidence: 99%

Robust Sampling of Defective Pathways in Alzheimer’s Disease. Implications in Drug Repositioning

Fernández-Martínez

Álvarez-Machancoses

Andrés-Galiana

et al. 2020

IJMS

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“…A number of the identified genes such as ACAT1 (Table 1 ) and SGIP1 (Table 2 ) confer risk for diseases or endophenotypes that are predominantly specific to the human species, such as complex psychiatric disorders [ 46 , 47 ]. SULT1A4 (Table 1 ) plays a critical role in neurotransmitter metabolism in the human brain and is also linked to neurodegeneration [ 48 ]. APOA2 (Additional file 4 ) along with several other lipoproteins is linked to cognitive health [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Link between short tandem repeats and translation initiation site selection

et al. 2018

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BackgroundDespite their vast biological implication, the relevance of short tandem repeats (STRs)/microsatellites to the protein-coding gene translation initiation sites (TISs) remains largely unknown.MethodsWe performed an Ensembl-based comparative genomics study of all annotated orthologous TIS-flanking sequences in human and 46 other species across vertebrates, on the genomic DNA and cDNA platforms (755,956 TISs), aimed at identifying human-specific STRs in this interval. The collected data were used to examine the hypothesis of a link between STRs and TISs. BLAST was used to compare the initial five amino acids (excluding the initial methionine), codons of which were flanked by STRs in human, with the initial five amino acids of all annotated proteins for the orthologous genes in other vertebrates (total of 5,314,979 pair-wise TIS comparisons on the genomic DNA and cDNA platforms) in order to compare the number of events in which human-specific and non-specific STRs occurred with homologous and non-homologous TISs (i.e., ≥ 50% and < 50% similarity of the five amino acids).ResultsWe detected differential distribution of the human-specific STRs in comparison to the overall distribution of STRs on the genomic DNA and cDNA platforms (Mann Whitney U test p = 1.4 × 10−11 and p < 7.9 × 10−11, respectively). We also found excess occurrence of non-homologous TISs with human-specific STRs and excess occurrence of homologous TISs with non-specific STRs on both platforms (p < 0.00001).ConclusionWe propose a link between STRs and TIS selection, based on the differential co-occurrence rate of human-specific STRs with non-homologous TISs and non-specific STRs with homologous TISs.Electronic supplementary materialThe online version of this article (10.1186/s40246-018-0181-3) contains supplementary material, which is available to authorized users.

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“…NVL), confer risk for diseases that are predominantly specific to the human species, such as schizophrenia and bipolar disorder (Wang et al 2015). Neurodegeneration is another example linked to genes such as SULT1A3 (Butcher et al 2017). In another remarkable example, TBR1 is involved in FOXP2 gene expression, which has pivotal role in speech and language in human (Becker et al 2018).…”

Section: Discussionmentioning

confidence: 99%

Link Between Short tandem Repeats and Translation Initiation Site Selection

Arabfard

Kavousi

Delbari

et al. 2018

Preprint

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Recent work in yeast and humans suggest that evolutionary divergence in cis-regulatory sequences impact translation initiation sites (TISs). Cis-elements can also affect the efficacy and amount of protein synthesis. Despite their vast biological implication, the landscape and relevance of short tandem repeats (STRs)/microsatellites to the human protein-coding gene TISs remain largely unknown. Here we characterized the STR distribution at the 120 bp cDNA sequence upstream of all annotated human protein-coding gene TISs based on the Ensembl database. Furthermore, we performed a comparative genomics study of all annotated orthologous TIS-flanking sequences across 47 vertebrate species (755,956 transcripts), aimed at identifying human-specific STRs in this interval. We also hypothesized that STRs may be used as genetic codes for the initiation of translation. The initial five amino acid sequences (excluding the initial methionine) that were flanked by STRs in human were BLASTed against the initial orthologous five amino acids in other vertebrate species (2,025, in order to compare the number of events in which human-specific and non-specific STRs occurred with homologous and non-homologous TISs (i.e. ≥50% and <50% similarity of the five amino acids). We characterized human-specific STRs and a bias of this compartment in comparison to the overall (human-specific and non-specific) distribution of STRs (Mann Whitney p=1.4 x 10 -11 ). We also found significant enrichment of non-homologous TISs flanked by human-specific STRs (p<0.00001). In conclusion, our data indicate a link between STRs and TIS selection, which is supported by differential evolution of the human-specific STRs in the TIS upstream flanking sequence.

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Sulfotransferase 1A3/4 copy number variation is associated with neurodegenerative disease

Cited by 23 publications

References 53 publications

Robust Sampling of Defective Pathways in Alzheimer’s Disease. Implications in Drug Repositioning

Robust Sampling of Defective Pathways in Alzheimer’s Disease. Implications in Drug Repositioning

Link between short tandem repeats and translation initiation site selection

Link Between Short tandem Repeats and Translation Initiation Site Selection

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