Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. We sequenced and analyzed the whole genomes of 27 HCCs, 25 of which were associated with hepatitis B or C virus infections, including two sets of multicentric tumors. Although no common somatic mutations were identified in the multicentric tumor pairs, their whole-genome substitution patterns were similar, suggesting that these tumors developed from independent mutations, although their shared etiological backgrounds may have strongly influenced their somatic mutation patterns.

High-resolution characterization of a hepatocellular carcinoma genome.

Hepatocellular carcinoma, one of the most common virus-associated cancers, is the third most frequent cause of cancer-related death worldwide. By massively parallel sequencing of a primary hepatitis C virus-positive hepatocellular carcinoma (36× coverage) and matched lymphocytes (>28× coverage) from the same individual, we identified more than 11,000 somatic substitutions of the tumor genome that showed predominance of T>C/A>G transition and a decrease of the T>C substitution on the transcribed strand, suggesting preferential DNA repair. Gene annotation enrichment analysis of 63 validated non-synonymous substitutions revealed enrichment of phosphoproteins.

Collection of Macaca fascicularis cDNAs derived from bone marrow, kidney, liver, pancreas, spleen, and thymus.

Background: Consolidating transcriptome data of non-human primates is essential to annotate primate genome sequences, and will facilitate research using non-human primates in the genomic era. Macaca fascicularis is a macaque monkey that is commonly used for biomedical and ecological research.

Findings: We constructed cDNA libraries of Macaca fascicularis, derived from tissues obtained from bone marrow, liver, pancreas, spleen, and thymus of a young male, and kidney of a young female.

Casein kinase I{gamma}2 down-regulates trafficking of ceramide in the synthesis of sphingomyelin.

Intracellullar trafficking of lipids is fundamental to membrane biogenesis. For the synthesis of sphingomyelin, ceramide is transported from the endoplasmic reticulum to the Golgi apparatus by the ceramide transfer protein CERT. CERT is phosphorylated by protein kinase D at S132 and subsequently multiple times in a serine-repeat motif, resulting in its inactivation.

Extensive expansion and diversification of the chemokine gene family in zebrafish: identification of a novel chemokine subfamily CX.

Background: The chemokine family plays important roles in cell migration and activation. In humans, at least 44 members are known. Based on the arrangement of the four conserved cysteine residues, chemokines are now classified into four subfamilies, CXC, CC, XC and CX3C.

Large-scale analysis of Macaca fascicularis transcripts and inference of genetic divergence between M. fascicularis and M. mulatta.

Background: Cynomolgus macaques (Macaca fascicularis) are widely used as experimental animals in biomedical research and are closely related to other laboratory macaques, such as rhesus macaques (M. mulatta). We isolated 85,721 clones and determined 9407 full-insert sequences from cynomolgus monkey brain, testis, and liver.

Mapping of chimpanzee full-length cDNAs onto the human genome unveils large potential divergence of the transcriptome.

The genetic basis of the phenotypic difference between human and chimpanzee is one of the most actively pursued issues in current genomics. Although the genomic divergence between the two species has been described, the transcriptomic divergence has not been well documented. Thus, we newly sequenced and analyzed chimpanzee full-length cDNAs (FLcDNAs) representing 87 protein-coding genes.

Identification of a novel CXCL1-like chemokine gene in macaques and its inactivation in hominids.

Chemokines are a rapidly evolving cytokine gene family. Because of various genome rearrangements after divergence of primates and rodents, humans and mice have different sets of chemokine genes, with humans having members outnumbering those of mice. Here, we report the occurrence of lineage-specific chemokine gene generation or inactivation events within primates.

Aberrant termination of reproduction-related TMEM30C transcripts in the hominoids.

Finding genetic novelties that may contribute to human-specific physiology and diseases is a key issue of current biomedical studies. TMEM30C is a gene containing two transmembrane (TM) domains and homologous to the yeast CDC50 family, which is related to polarized cell division. It is conserved among mammals along with two other paralogs, TMEM30A and TMEM30B.

Substitution rate and structural divergence of 5'UTR evolution: comparative analysis between human and cynomolgus monkey cDNAs.

The substitution rate and structural divergence in the 5'-untranslated region (UTR) were investigated by using human and cynomolgus monkey cDNA sequences. Due to the weaker functional constraint in the UTR than in the coding sequence, the divergence between humans and macaques would provide a good estimate of the nucleotide substitution rate and structural divergence in the 5'UTR. We found that the substitution rate in the 5'UTR (K5UTR) averaged approximately 10%-20% lower than the synonymous substitution rate (Ks).

Comparative DNA sequence analysis of mouse and human CC chemokine gene clusters.

The CC chemokines are a closely related subfamily of the chemokine superfamily. Most of the CC chemokine genes form a cluster on chromosome 11 in mice and chromosome 17 in humans. To date, 11 and 16 functional genes have been localized within the mouse and human clusters, respectively.

Cynomolgus monkey testicular cDNAs for discovery of novel human genes in the human genome sequence.

Background: In order to contribute to the establishment of a complete map of transcribed regions of the human genome, we constructed a testicular cDNA library for the cynomolgus monkey, and attempted to find novel transcripts for identification of their human homologues.

Result: The full-insert sequences of 512 cDNA clones were determined. Ultimately we found 302 non-redundant cDNAs carrying open reading frames of 300 bp-length or longer.

Search for genes positively selected during primate evolution by 5'-end-sequence screening of cynomolgus monkey cDNAs.

It is possible to assess positive selection by using the ratio of K(a) (nonsynonymous substitutions per plausible nonsynonymous sites) to K(s) (synonymous substitutions per plausible synonymous sites). We have searched candidate genes positively selected during primate evolution by using 5'-end sequences of 21,302 clones derived from cynomolgus monkey (Macaca fascicularis) brain cDNA libraries. Among these candidates, 10 genes that had not been shown by previous studies to undergo positive selection exhibited a K(a)/K(s) ratio > 1.

Prediction of unidentified human genes on the basis of sequence similarity to novel cDNAs from cynomolgus monkey brain.

Background: The complete assignment of the protein-coding regions of the human genome is a major challenge for genome biology today. We have already isolated many hitherto unknown full-length cDNAs as orthologs of unidentified human genes from cDNA libraries of the cynomolgus monkey (Macaca fascicularis) brain (parietal lobe and cerebellum). In this study, we used cDNA libraries of three other parts of the brain (frontal lobe, temporal lobe and medulla oblongata) to isolate novel full-length cDNAs.