We describe a new basis for the construction of a genetic linkage map of the human genome. The basic principle of the mapping scheme is to develop, by recombinant DNA techniques, random single-copy DNA probes capable of detecting DNA sequence polymorphisms, when hybridized to restriction digests of an individual's DNA. Each of these probes will define a locus. Loci can be expanded or contracted to include more or less polymorphism by further application of recombinant DNA technology. Suitably polymorphic loci can be tested for linkage relationships in human pedigrees by established methods; and loci can be arranged into linkage groups to form a true genetic map of "DNA marker loci." Pedigrees in which inherited traits are known to be segregating can then be analyzed, making possible the mapping of the gene(s) responsible for the trait with respect to the DNA marker loci, without requiring direct access to a specified gene's DNA. For inherited diseases mapped in this way, linked DNA marker loci can be used predictively for genetic counseling.

Construction of a genetic linkage map in man using restriction fragment length polymorphisms.

https://www.cell.com/cell/pdf/0092-8674%2893%2990719-7.pdf

p53-dependent apoptosis modulates the cytotoxicity of anticancer agents

https://www.cell.com/cell/pdf/0092-8674(81)90282-8.pdf

SV40-transformed simian cells support the replication of early SV40 mutants.

Sizing and mapping of early adenovirus mRNAs by gel electrophoresis of S1 endonuclease-digested hybrids

In the last decade, basic cancer research has produced remarkable advances in our understanding of cancer biology and cancer genetics. Among the most important of these advances is the realization that apoptosis and the genes that control it have a profound effect on the malignant phenotype. For example, it is now clear that some oncogenic mutations disrupt apoptosis, leading to tumor initiation, progression or metastasis. Conversely, compelling evidence indicates that other oncogenic changes promote apoptosis, thereby producing selective pressure to override apoptosis during multistage carcinogenesis. Finally, it is now well documented that most cytotoxic anticancer agents induce apoptosis, raising the intriguing possibility that defects in apoptotic programs contribute to treatment failure. Because the same mutations that suppress apoptosis during tumor development also reduce treatment sensitivity, apoptosis provides a conceptual framework to link cancer genetics with cancer therapy. An intense research effort is uncovering the underlying mechanisms of apoptosis such that, in the next decade, one envisions that this information will produce new strategies to exploit apoptosis for therapeutic benefit.

Apoptosis in cancer

The Cold Spring Harbor Symposia on Quantitative Biology bring together scientists from all over the
world to present and evaluate new data and ideas in rapidly moving areas of biological research. Each year, a topic is chosen that appears to be at a stage where general and intensive scrutiny and review are needed. Criteria for selection of topics are numerous, but they include the rate of progress in a given field, how recent
research is highlighting connections between fundamental biological mechanisms, and the potential applications of the new discoveries to human health and society. Cold Spring Harbor Laboratory selected the theme of The Biology of Plants for the historic 77th Symposium in the series. Plants are integral to human well being, and many species have been domesticated for more than 10,000 years. Evidence of plant scientific investigation and classification can be found in ancient texts from cultures around the world (Chinese, Indian, Greco-Roman, Muslim, etc.), whereas early modern botany can be traced to the late 15th and early 16th centuries in Europe. During the past several decades, plant biology has been revolutionized first by molecular biology and then by the genomic era. The model organism Arabidopsis thaliana has proved to be an invaluable tool for investigation into fundamental processes in plant biology,
many of which share commonalities with animal biology. Plant-specific processes from reproduction to
immunity and second messengers have also yielded to extensive investigation. With the genomes of more than 30 plant species now available and many more planned in the near future, the impact on our understanding of plant evolution and biology continues to grow. Our increased ability to engineer plant species to a variety of ends may provide novel solutions to ensure adequate and reliable food production and renewable energy even as climate change impacts our environment. The decision to focus the 2012 Symposium on plant science reflected the enormous research progress achieved in recent years andwas intended to provide a broad synthesis of the current state of the field, setting the
stage for future discoveries and application. This is the first Symposium in this historic series that focused exclusively on the botanical sciences. The Symposium spanned a broad range of areas of investigation including genetics, biochemistry, molecular and cell biology, developmental biology, physiology, and population/
evolution studies at levels ranging from the single cell to the entire organismand from single genes to
genomes; plant-specific processes and pathways featured broadly throughout the meeting. Effort was made to balance fundamental biological discoveries with applications relevant to societal well being including improved
crops, fuel, and habitat.

/pdf/the-biology-of-plants-1rrwvyxp78.pdf

The Biology of Plants

Physical mapping of temperature-sensitive mutations of adenoviruses.

Mutations that allow human Ad2 and Ad5 to express late genes in monkey cells map in the viral gene encoding the 72K DNA binding protein.

Plasmids expressing partial adenovirus early region 1A (E1A) coding sequences were tested for activities which facilitate in vitro establishment (immortalization) of primary baby rat kidney cells and which enable the T24 Harvey ras-related oncogene and the polyomavirus middle T antigen (pmt) gene to transform primary baby rat kidney cells. E1A cDNAs expressing the 289- and 243-amino acid proteins expressed both E1A transforming functions. Mutant hrA, which encodes a 140-amino acid protein derived from the amino-terminal domain shared by the 289- and 243-amino acid proteins, enabled ras (but not pmt) to transform and facilitated in vitro establishment to a low, but detectable, extent. These studies suggest that E1A functions which collaborate with ras oncogenes and those which facilitate establishment are linked. Furthermore, E1A transforming functions are not associated with activities of the 289-amino acid E1A proteins required for efficient transcriptional activation of viral early region promoters.

T. Grodzicker

Papers

The Biology of Plants

Physical mapping of temperature-sensitive mutations of adenoviruses.

Mutations that allow human Ad2 and Ad5 to express late genes in monkey cells map in the viral gene encoding the 72K DNA binding protein.

Physical mapping of temperature-sensitive mutations of adenoviruses.

Adenovirus E1A coding sequences that enable ras and pmt oncogenes to transform cultured primary cells.