Biomedical subjects

Gregory Theiler

Publications and source records attributed to Gregory Theiler.

4 recordsLinked to original sources

PubMed2005

Identification of CT46/HORMAD1, an immunogenic cancer/testis antigen encoding a putative meiosis-related protein.

Transcripts with ESTs derived exclusively or predominantly from testis, and not from other normal tissues, are likely to be products of genes with testis-restricted expression, and are thus potential cancer/testis (CT) antigen genes. A list of 371 genes with such characteristics was compiled by analyzing publicly available EST databases. RT-PCR analysis of normal and tumor tissues was performed to validate an initial selection of 20 of these genes. Several new CT and CT-like genes were identified. One of these, CT46/HORMAD1, is expressed strongly in testis and weakly in placenta; the highest level of expression in other tissues is <1% of testicular expression. The CT46/HORMAD1 gene was expressed in 31% (34/109) of the carcinomas examined, with 11% (12/109) showing expression levels >10% of the testicular level of expression. CT46/HORMAD1 is a single-copy gene on chromosome 1q21.3, encoding a putative protein of 394 aa. Conserved protein domain analysis identified a HORMA domain involved in chromatin binding. The CT46/HORMAD1 protein was found to be homologous to the prototype HORMA domain-containing protein, Hop1, a yeast meiosis-specific protein, as well as to asy1, a meiotic synaptic mutant protein in Arabidopsis thaliana.

Amino Acid Sequence↗

PubMed2005

Identification of cancer/testis-antigen genes by massively parallel signature sequencing.

Massively parallel signature sequencing (MPSS) generates millions of short sequence tags corresponding to transcripts from a single RNA preparation. Most MPSS tags can be unambiguously assigned to genes, thereby generating a comprehensive expression profile of the tissue of origin. From the comparison of MPSS data from 32 normal human tissues, we identified 1,056 genes that are predominantly expressed in the testis. Further evaluation by using MPSS tags from cancer cell lines and EST data from a wide variety of tumors identified 202 of these genes as candidates for encoding cancer/testis (CT) antigens. Of these genes, the expression in normal tissues was assessed by RT-PCR in a subset of 166 intron-containing genes, and those with confirmed testis-predominant expression were further evaluated for their expression in 21 cancer cell lines. Thus, 20 CT or CT-like genes were identified, with several exhibiting expression in five or more of the cancer cell lines examined. One of these genes is a member of a CT gene family that we designated as CT45. The CT45 family comprises six highly similar (>98% cDNA identity) genes that are clustered in tandem within a 125-kb region on Xq26.3. CT45 was found to be frequently expressed in both cancer cell lines and lung cancer specimens. Thus, MPSS analysis has resulted in a significant extension of our knowledge of CT antigens, leading to the discovery of a distinctive X-linked CT-antigen gene family.

Antigens, Neoplasm↗

PubMed2004

Digital expression profiles of human endogenous retroviral families in normal and cancerous tissues.

Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections that became fixed in the germ line DNA millions of years ago. The fact that humoral and cellular immune responses against HERV-encoded proteins have been identified in cancer patients suggests that these antigens might be used in cancer immunotherapy or diagnosis. We analyzed the digital expression patterns of the HERV-K (HML-2), -W, -H and -E families in normal and cancerous tissues. Thirty-one proviral members of the HERV-K family and one representative each for the other HERV families were used as probes to search human EST data. Matching of HERV proviruses to ESTs was HERV family-specific and the expression profiles of the HERV families distinct. The HERV-K family was expressed in normal tissues such as muscle, skin and brain, as well as in germ cell tumors and other cancerous tissues. HERV-H was the only family expressed in cancers of the intestine, bone marrow, bladder and cervix, and was more highly expressed than the other families in cancers of the stomach, colon and prostate. In contrast, HERV-W was predominantly expressed in normal placenta. Expression patterns were confirmed by MPSS (massively parallel signature sequencing) data where available. For the HERV-K family, we mapped most ESTs to their corresponding proviruses and assessed the coding capacities of the matched proviruses. This study shows that HERV families are more widely expressed than originally thought and that some members of the HERV-K and -H families could encode targets for cancer immunotherapy.

Chromosome Mapping↗

PubMed2003

eVOC: a controlled vocabulary for unifying gene expression data.

Expression data contribute significantly to the biological value of the sequenced human genome, providing extensive information about gene structure and the pattern of gene expression. ESTs, together with SAGE libraries and microarray experiment information, provide a broad and rich view of the transcriptome. However, it is difficult to perform large-scale expression mining of the data generated by these diverse experimental approaches. Not only is the data stored in disparate locations, but there is frequent ambiguity in the meaning of terms used to describe the source of the material used in the experiment. Untangling semantic differences between the data provided by different resources is therefore largely reliant on the domain knowledge of a human expert. We present here eVOC, a system which associates labelled target cDNAs for microarray experiments, or cDNA libraries and their associated transcripts with controlled terms in a set of hierarchical vocabularies. eVOC consists of four orthogonal controlled vocabularies suitable for describing the domains of human gene expression data including Anatomical System, Cell Type, Pathology and Developmental Stage. We have curated and annotated 7016 cDNA libraries represented in dbEST, as well as 104 SAGE libraries,with expression information,and provide this as an integrated, public resource that allows the linking of transcripts and libraries with expression terms. Both the vocabularies and the vocabulary-annotated libraries can be retrieved from http://www.sanbi.ac.za/evoc/. Several groups are involved in developing this resource with the aim of unifying transcript expression information.

Animals↗