Project description:The eutherian connexins were characterized as protein constituents of gap junctions implicated in cell-cell communications between adjoining cells in multiple cell types, regulation of major physiological processes and disease pathogeneses. However, conventional connexin gene and protein classifications could be regarded as unsuitable in descriptions of comprehensive eutherian connexin gene data sets, due to ambiguities and inconsistencies in connexin gene and protein nomenclatures. Using eutherian comparative genomic analysis protocol and 35 public eutherian reference genomic sequence data sets, the present analysis attempted to update and revise comprehensive eutherian connexin gene data sets, and address and resolve major discrepancies in their descriptions. Among 631 potential coding sequences, the tests of reliability of eutherian public genomic sequences annotated, in aggregate, 349 connexin complete coding sequences. The most comprehensive curated eutherian connexin gene data set described 21 major gene clusters, 4 of which included evidence of differential gene expansions. For example, the present gene annotations initially described human CXNK1 gene and annotated 22 human connexin genes. Phylogenetic tree calculations and calculations of pairwise nucleotide sequence identity patterns proposed revised and updated phylogenetic classification of eutherian connexin genes. Therefore, the present study integrating gene annotations, phylogenetic analysis and protein molecular evolution analysis proposed new nomenclature of eutherian connexin genes and proteins.
Project description:The present study made attempts to update and revise eutherian kallikrein genes implicated in major physiological and pathological processes and in medical molecular diagnostics. Using eutherian comparative genomic analysis protocol and free available genomic sequence assemblies, the tests of reliability of eutherian public genomic sequences annotated most comprehensive curated third party data gene data set of eutherian kallikrein genes including 121 complete coding sequences among 335 potential coding sequences. The present analysis first described 13 major gene clusters of eutherian kallikrein genes, and explained their differential gene expansion patterns. One updated classification and nomenclature of eutherian kallikrein genes was proposed, as new framework of future experiments.
Project description:The present study proposed updated and standardized classification and nomenclature of eutherian adiponectin genes implicated in regulation of systemic metabolism and inflammation and activation of classical complement pathway. The revisions of comprehensive adiponectin gene data sets used eutherian comparative genomic analysis protocol and public reference genomic sequence assemblies. Among 438 potential coding sequences, the tests of reliability of eutherian public genomic sequences annotated most comprehensive curated third-party data gene data set of eutherian adiponectin genes that included 211 complete coding sequences. There were 18 major gene clusters of eutherian adiponectin genes described, one of which included evidence of differential gene expansions. For example, the present analysis initially described human ADIF2 and ADIR genes. Finally, the tests of protein molecular evolution using relative synonymous codon usage statistics confirmed protein primary structure similarities between eutherian adiponectins and tumor necrosis factor ligands.
Project description:BACKGROUND:The eutherian fibroblast growth factors were implicated as key regulators in developmental processes. However, there were major disagreements in descriptions of comprehensive eutherian fibroblast growth factors gene data sets including either 18 or 22 homologues. The present analysis attempted to revise and update comprehensive eutherian fibroblast growth factor gene data sets, and address and resolve major discrepancies in their descriptions using eutherian comparative genomic analysis protocol and 35 public eutherian reference genomic sequence data sets. RESULTS:Among 577 potential coding sequences, the tests of reliability of eutherian public genomic sequences annotated most comprehensive curated eutherian third-party data gene data set of fibroblast growth factor genes including 267 complete coding sequences. The present study first described 8 superclusters including 22 eutherian fibroblast growth factor major gene clusters, proposing their updated classification and nomenclature. CONCLUSIONS:The integrated gene annotations, phylogenetic analysis and protein molecular evolution analysis argued that comprehensive eutherian fibroblast growth factor gene data set classifications included 22 rather than 18 homologues.
Project description:BackgroundThe homologues of human disease genes are expected to contribute to better understanding of physiological and pathogenic processes. We made use of the present availability of vertebrate genomic sequences, and we have conducted the most comprehensive comparative genomic analysis of the prion protein gene PRNP and its homologues, shadow of prion protein gene SPRN and doppel gene PRND, and prion testis-specific gene PRNT so far.ResultsWhile the SPRN and PRNP homologues are present in all vertebrates, PRND is known in tetrapods, and PRNT is present in primates. PRNT could be viewed as a TE-associated gene. Using human as the base sequence for genomic sequence comparisons (VISTA), we annotated numerous potential cis-elements. The conserved regions in SPRNs harbour the potential Sp1 sites in promoters (mammals, birds), C-rich intron splicing enhancers and PTB intron splicing silencers in introns (mammals, birds), and hsa-miR-34a sites in 3'-UTRs (eutherians). We showed the conserved PRNP upstream regions, which may be potential enhancers or silencers (primates, dog). In the PRNP 3'-UTRs, there are conserved cytoplasmic polyadenylation element sites (mammals, birds). The PRND core promoters include highly conserved CCAAT, CArG and TATA boxes (mammals). We deduced 42 new protein primary structures, and performed the first phylogenetic analysis of all vertebrate prion genes. Using the protein alignment which included 122 sequences, we constructed the neighbour-joining tree which showed four major clusters, including shadoos, shadoo2s and prion protein-likes (cluster 1), fish prion proteins (cluster 2), tetrapode prion proteins (cluster 3) and doppels (cluster 4). We showed that the entire prion protein conformationally plastic region is well conserved between eutherian prion proteins and shadoos (18-25% identity and 28-34% similarity), and there could be a potential structural compatibility between shadoos and the left-handed parallel beta-helical fold.ConclusionIt is likely that the conserved genomic elements identified in this analysis represent bona fide cis-elements. However, this idea needs to be confirmed by functional assays in transgenic systems.
Project description:We used human endometrial stromal fibroblast cell line to perform an siRNA knockdown coupled with RNA-seq screen of a series of transcription factors that gained expression in the endometrial tissue of Eutherian mammals.
Project description:We used human endometrial stromal fibroblast cell line to perform an siRNA knockdown coupled with RNA-seq screen of a series of transcription factors that gained expression in the endometrial tissue of Eutherian mammals.