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An understanding of the regulatory mechanisms responsible for pluripotency in embryonic stem cells (ESCs) is critical for realizing their potential in medicine and science. Significant similarities exist among ESCs harvested from different species, yet major differences have also been observed. Here, by cross-species analysis of a large set of functional categories and all transcription factors and...
Hypoxanthine phosphoribosyltransferase (HPRT1) is a key enzyme in the purine salvage pathway, and mutations in HPRT1 cause Lesch–Nyhan disease. The studies described here utilized targeted comparative mapping and sequencing, in conjunction with database searches, to assemble a collection of 53 HPRT1 homologs from 28 vertebrates. Phylogenetic analysis of these homologs revealed that the HPRT gene family...
The number of mRNAs and proteins that can be produced from a single gene is known to be increased by the number of start sites and by multiple splicing of products. A few genes have been found to generate extraordinarily large numbers of splicing isoforms. In the human, the largest number, nearly 2000 mRNA isoforms, has been reported for the neurexin 3α gene. However, the biological significance of...
While isolating morphine-dependence-related genes with differential display, we cloned a novel human gene, zinc finger CCHC-type and RNA-binding motif 1 (ZCRB1, alias MADP-1) encoding a nuclear protein (217 residues). The ZCRB1 gene consists of eight exons and seven introns. It is mapped to 12q12, which is within a locus reported for Parkinson disease (M. Funayama et al., Ann. Neurol. 51 (2002) 296–301)...
We report the genomic DNA sequence of a single chromosome (linkage group 22; LG22) of the small teleost fish medaka (Oryzias latipes) as a first whole chromosome sequence from a non-mammalian vertebrate. The order and orientation of 633 protein-coding genes were deduced from 18,803,338 bp of DNA sequence, providing the opportunity to analyze chromosome evolution of vertebrate genomes by direct comparison...
The human SIRT3 gene contains an intronic VNTR enhancer whose variability is correlated with life span. The SIRT3 5′ flanking region encompasses the PSMD13 gene encoding the p40.5 regulator subunit of the 26S proteasome. Proteasome is a multicatalytic proteinase whose function declines with aging. SIRT3 and PSMD13 are linked in a head-to-head configuration (788-bp intergenic region). The molecular...
Current methods of detecting hepatitis B virus (HBV) mutations are time consuming, labor intensive, and not suitable for screening large numbers of samples. A multiplex real-time PCR approach presented in this article is a hepatitis B virus quantification method that employs the SYBR Green I dye in conjunction with wild-type HBV sequence-specific locked nucleic acid (LNA) probes. The three short LNA...
A modern concept for the development of novel antiparasitic drugs is the combination of bioinformatics and chemoinformatics approaches. This covers, for example, the identification of target proteins serving as molecular points of attack for parasiticides—the idea is that, owing to some essential role, inhibition of a target protein should eradicate the parasite. To prevent toxicity problems for vertebrate...
To understand how genes are distributed on chromosomes we bring new insights into gene positional clustering and its properties. We have made a large-scale analysis of three types of differentiation and we observed that genes that subsequently enter into different cell processes are positionally clustered on chromosomes. Genes from the clusters are transcribed subsequently with respect to time kinetics...
With the development of new high-information content fingerprinting techniques for constructing BAC-based physical maps, physical map construction is accelerating and it is important to determine which methodologies work best. In a recent publication (Z. Xu et al., 2004, Genomics 84:941-951), Xu et al. evaluated five different techniques (one agarose-based and four using multiple enzymes) and concluded...
We isolated and characterized a cluster of platypus DMRT genes and compared their arrangement, location, and sequence across vertebrates. The DMRT gene cluster on human 9p24.3 harbors, in order, DMRT1, DMRT3, and DMRT2, which share a DM domain. DMRT1 is highly conserved and involved in sexual development in vertebrates, and deletions in this region cause sex reversal in humans. Sequence comparisons...
High-resolution physically ordered gene maps for equine homologs of human chromosome 5 (HSA5), viz., horse chromosomes 14 and 21 (ECA14 and ECA21), were generated by adding 179 new loci (131 gene-specific and 48 microsatellites) to the existing maps of the two chromosomes. The loci were mapped primarily by genotyping on a 5000-rad horse×hamster radiation hybrid panel, of which 28 were mapped by fluorescence...
Our previously reported cDNA array datasets from neonatal wild-type and Cx43 −/− (approved gene symbol Gja1) mouse brains were further analyzed to identify underlying interlinkages in the brain transcriptome. The analysis revealed that no gene cohort sharing either primary function or chromosomal location was significantly altered (up-and down-regulation were roughly balanced) in Cx43 ...
To elucidate the functional significance of genome multiplication in somatic tissues, we performed a large-scale analysis of ploidy-associated changes in expression of non-tissue-specific (i.e., broadly expressed) genes in the heart and liver of human and mouse (6585 homologous genes were analyzed). These species have inverse patterns of polyploidization in cardiomyocytes and hepatocytes. The between-species...
Human endogenous retroviral sequences family P (HERV-P) proviral sequences have been located within the human genome. Here, we identify and analyze novel putative structural genes of HERV-P in primates, human tissues, and cancer cells with an aim toward better understanding their evolutionary relationships and transcriptional potential. The expression pattern of HERV-P structural genes indicates that...
TP53 (tumor protein p53; p53) regulates its target genes under various cellular stresses. By combining chromatin immunoprecipitation with oligonucleotide microarrays, we have mapped binding sites of p53 (p53-BS) in the genome of HCT116 human colon carcinoma cells, along with those of acetylated H3, acetylated H4, and methylated H3-K4. We analyzed a 30-Mb portion of the human genome selected as a representative...
Phosphoinositide lipids generated at the cell membrane are a key component of a variety of signaling pathways. Among several inositol phosphatases that regulate the availability of signaling phosphoinositide lipids, the type II SH2-domain-containing inositol 5-phosphatase (SHIP2; approved gene symbol Inppl1) is believed to have multiple functions, including the regulation of insulin signaling and...
We report the construction of a 1.5-Mb-resolution radiation hybrid map of the domestic cat genome. This new map includes novel microsatellite loci and markers derived from the 2X genome sequence that target previous gaps in the feline–human comparative map. Ninety-six percent of the 1793 cat markers we mapped have identifiable orthologues in the canine and human genome sequences. The updated autosomal...
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