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Biomedical subjects

T G Wolfsberg

Publications and source records attributed to T G Wolfsberg.

At least 19 recordsLinked to original sources
PubMed2001

Guide to the draft human genome.

There are a number of ways to investigate the structure, function and evolution of the human genome. These include examining the morphology of normal and abnormal chromosomes, constructing maps of genomic landmarks, following the genetic transmission of phenotypes and DNA sequence variations, and characterizing thousands of individual genes. To this list we can now add the elucidation of the genomic DNA sequence, albeit at 'working draft' accuracy. The current challenge is to weave together these disparate types of data to produce the information infrastructure needed to support the next generation of biomedical research. Here we provide an overview of the different sources of information about the human genome and how modern information technology, in particular the internet, allows us to link them together.

Amino Acid Sequence↗
PubMed2001

Web alert. Genetics of disease.

A selection of World Wide Web sites relevant to papers published in this issue of Current Opinion in Genetics & Development.

Databases, Factual↗
PubMed1999

Candidate regulatory sequence elements for cell cycle-dependent transcription in Saccharomyces cerevisiae.

Recent developments in genome-wide transcript monitoring have led to a rapid accumulation of data from gene expression studies. Such projects highlight the need for methods to predict the molecular basis of transcriptional coregulation. A microarray project identified the 420 yeast transcripts whose synthesis displays cell cycle-dependent periodicity. We present here a statistical technique we developed to identify the sequence elements that may be responsible for this cell cycle regulation. Because most gene regulatory sites contain a short string of highly conserved nucleotides, any such strings that are involved in gene regulation will occur frequently in the upstream regions of the genes that they regulate, and rarely in the upstream regions of other genes. Our strategy therefore utilizes statistical procedures to identify short oligomers, five or six nucleotides in length, that are over-represented in upstream regions of genes whose expression peaks at the same phase of the cell cycle. We report, with a high level of confidence, that 9 hexamers and 12 pentamers are over-represented in the upstream regions of genes whose expression peaks at the early G(1), late G(1), S, G(2), or M phase of the cell cycle. Some of these sequence elements show a preference for a particular orientation, and others, through a separate statistical test, for a particular position upstream of the ATG start codon. The finding that the majority of the statistically significant sequence elements are located in late G(1) upstream regions correlates with other experiments that identified the late G(1)/early S boundary as a vital cell cycle control point. Our results highlight the importance of MCB, an element implicated previously in late G(1)/early S gene regulation, as most of the late G(1) oligomers contain the MCB sequence or variations thereof. It is striking that most MCB-like sequences localize to a specific region upstream of the ATG start codon. Additional sequences that we have identified may be important for regulation at other phases of the cell cycle.

5' Untranslated Regions↗
PubMed1998

A genome-wide transcriptional analysis of the mitotic cell cycle.

Progression through the eukaryotic cell cycle is known to be both regulated and accompanied by periodic fluctuation in the expression levels of numerous genes. We report here the genome-wide characterization of mRNA transcript levels during the cell cycle of the budding yeast S. cerevisiae. Cell cycle-dependent periodicity was found for 416 of the 6220 monitored transcripts. More than 25% of the 416 genes were found directly adjacent to other genes in the genome that displayed induction in the same cell cycle phase, suggesting a mechanism for local chromosomal organization in global mRNA regulation. More than 60% of the characterized genes that displayed mRNA fluctuation have already been implicated in cell cycle period-specific biological roles. Because more than 20% of human proteins display significant homology to yeast proteins, these results also link a range of human genes to cell cycle period-specific biological functions.

Cell Cycle↗
PubMed1997

A comparison of expressed sequence tags (ESTs) to human genomic sequences.

The Expressed Sequence Tag (EST) division of GenBank, dbEST, is a large repository of the data being generated by human genome sequencing centers. ESTs are short, single pass cDNA sequences generated from randomly selected library clones. The approximately 415 000 human ESTs represent a valuable, low priced, and easily accessible biological reagent. As many ESTs are derived from yet uncharacterized genes, dbEST is a prime starting point for the identification of novel mRNAs. Conversely, other genes are represented by hundreds of ESTs, a redundancy which may provide data about rare mRNA isoforms. Here we present an analysis of >1000 ESTs generated by the WashU-Merck EST project. These ESTs were collected by querying dbEST with the genomic sequences of 15 human genes. When we aligned the matching ESTs to the genomic sequences, we found that in one gene, 73% of the ESTs which derive from spliced or partially spliced transcripts either contain intron sequences or are spliced at previously unreported sites; other genes have lower percentages of such ESTs, and some have none. This finding suggests that ESTs could provide researchers with novel information about alternative splicing in certain genes. In a related analysis of pairs of ESTs which are reported to derive from a single gene, we found that as many as 26% of the pairs do not BOTH align with the sequence of the same gene. We suspect that some of these unusual ESTs result from artifacts in EST generation, and caution researchers that they may find such clones while analyzing sequences in dbEST.

Alternative Splicing↗
PubMed1997

ADAM 13: a novel ADAM expressed in somitic mesoderm and neural crest cells during Xenopus laevis development.

Embryonic development involves a series of cell adhesive interactions that provide mechanical and instructive information required for morphogenesis. The ADAMs family of membrane-anchored proteins, containing a disintegrin and metalloprotease domain, is well suited for participating in such developmental events. They encode not only a potential adhesive function, through an integrin-binding disintegrin domain, but also a potential antiadhesive function, through a zinc-dependent metalloprotease domain. In order to investigate the role of ADAMs in early development we cloned a cDNA encoding a novel member of the ADAM family from a Xenopus laevis neurula stage library. We call this cDNA, and the 915-amino-acid protein it encodes, ADAM 13, X-ADAM 13 RNA is expressed during embryogenesis from the midblastula stage through tadpole stage 45. X-ADAM 13 is localized to somitic mesoderm and cranial neural crest cells during gastrulation, neurulation, and in tail bud stages. Sequence analyses of the X-ADAM 13 metalloprotease and disintegrin domains indicate that the protein is likely to be involved in both proteolytic and cell-adhesive functions. The X-ADAM 13 sequence is most closely related to that of mouse meltrin alpha, which is implicated in myoblast fusion. Our data suggest that X-ADAM 13 may be involved in neural crest cell adhesion and migration as well as myoblast differentiation.

3T3 Cells↗