A Functional SNP Catalog of Overlapping mi RNA ‐Binding Sites in Genes Implicated in Prion Disease and Other Neurodegenerative Disorders
Author(s) -
Saba Reuben,
Medina Sarah J.,
Booth Stephanie A.
Publication year - 2014
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22627
Subject(s) - biology , single nucleotide polymorphism , genetics , gene , microrna , snp , disease , genotype , medicine , pathology
ABSTRACT The involvement of SNP s in mi RNA target sites remains poorly investigated in neurodegenerative disease. In addition to associations with disease risk, such genetic variations can also provide novel insight into mechanistic pathways that may be responsible for disease etiology and/or pathobiology. To identify SNP s associated specifically with degenerating neurons, we restricted our analysis to genes that are dysregulated in CA 1 hippocampal neurons of mice during early, preclinical phase of P rion disease. The 125 genes chosen are also implicated in other numerous degenerative and neurological diseases and disorders and are therefore likely to be of fundamental importance. We predicted those SNP s that could increase, decrease, or have neutral effects on mi RNA binding. This group of genes was more likely to possess DNA variants than were genes chosen at random. Furthermore, many of the SNP s are common within the human population, and could contribute to the growing awareness that mi RNA s and associated SNP s could account for detrimental neurological states. Interestingly, SNP s that overlapped mi RNA ‐binding sites in the 3′‐ UTR of GABA ‐receptor subunit coding genes were particularly enriched. Moreover, we demonstrated that SNP rs9291296 would strengthen mi R ‐26a‐5p binding to a highly conserved site in the 3′‐ UTR of gamma‐aminobutyric acid receptor subunit alpha‐4.
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