Identification of splice defects due to noncanonical splice site or deep‐intronic variants in ABCA4

Pathogenic variants in the ATP-binding cassette transporter A4 (ABCA4) gene cause a continuum of retinal disease phenotypes, including Stargardt disease. Noncanonical splice site (NCSS) and deep-intronic variants constitute a large fraction of disease-causing alleles, defining the functional consequences of which remains a challenge. We aimed to determine the effect on splicing of nine previously reported or unpublished NCSS variants, one near exon splice variant and nine deep-intronic variants in ABCA4, using in vitro splice assays in human embryonic kidney 293T cells. Reverse transcription-polymerase chain reaction and Sanger sequence analysis revealed splicing defects for 12 out of 19 variants. Four deep-intronic variants create pseudoexons or elongate the upstream exon. Furthermore, eight NCSS variants cause a partial deletion or skipping of one or more exons in messenger RNAs. Among the 12 variants, nine lead to premature stop codons and predicted truncated ABCA4 proteins. At least two deep-intronic variants affect splice enhancer and silencer motifs and, therefore, these conserved sequences should be carefully evaluated when predicting the outcome of NCSS and deep-intronic variants

CD44 polymorphisms and its variants, as an inconsistent marker in cancer investigations

Among cell surface markers, CD44 is considered the main marker for identifying and isolating the cancer stem cells (CSCs) among other cells and has attracted significant attention in a variety of research areas. Many studies have shown the essential roles of CD44 in initiation, metastasis, and tumorigenesis in different types of cancer; however, the validity of CD44 as a therapeutic or diagnostic target has not been fully confirmed in some other studies. Whereas the association of specific single nucleotide polymorphisms (SNPs) in the CD44 gene and related variants with cancer risk have been observed in clinical investigations, the significance of these findings remains controversial. Here, we aimed to provide an up-to-date overview of recent studies on the association of CD44 polymorphisms and its variants with different kinds of cancer to determine whether or not it can be used as an appropriate candidate for cancer tracking. © 2021 Elsevier B.V

A file group data replication algorithm for data grids

In recent years data grids have been deployed and grown in many scientific experiments and data centers. The deployment of such environments has allowed grid users to gain access to a large number of distributed data. Data replication is a key issue in a data grid and should be applied intelligently because it reduces data access time and bandwidth consumption for each grid site. Therefore this area will be very challenging as well as providing much scope for improvement. In this paper, we introduce a new dynamic data replication algorithm named Popular File Group Replication, PFGR which is based on three assumptions: first, users in a grid site (Virtual Organization) have similar interests in files and second, they have the temporal locality of file accesses and third, all files are read-only. Based on file access history and first assumption, PFGR builds a connectivity graph for a group of dependent files in each grid site and replicates the most popular group files to the requester grid site. After that, when a user of that grid site needs some files, they are available locally. The simulation results show that our algorithm increases performance by minimizing the mean job execution time and bandwidth consumption and avoids unnecessary replication.info:eu-repo/semantics/publishedVersio