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Biomedical subjects

R A George

Publications and source records attributed to R A George.

14 recordsLinked to original sources

Ceramic capillaries for use in microarray fabrication.

We have used ceramic capillary tips generally used in the microelectronics industry for the production of DNA microarrays. The ceramic tips improve the morphology of microarray elements, allow higher element density, and increase printing tip life over the customary slotted stainless-steel pins. Ceramic tips are less expensive than steel pins and allow printing from 1536-well sample source plates. In this work, we describe experiments that establish printing performance of the ceramic tips and hybridization experiments that show that DNA hybridization is unaffected by the choice of tip material.

Animals↗

The genome sequence of Drosophila melanogaster.

The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

Animals↗

Comparative genomics of the eukaryotes.

A comparative analysis of the genomes of Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae-and the proteins they are predicted to encode-was undertaken in the context of cellular, developmental, and evolutionary processes. The nonredundant protein sets of flies and worms are similar in size and are only twice that of yeast, but different gene families are expanded in each genome, and the multidomain proteins and signaling pathways of the fly and worm are far more complex than those of yeast. The fly has orthologs to 177 of the 289 human disease genes examined and provides the foundation for rapid analysis of some of the basic processes involved in human disease.

Animals↗

A BAC-based physical map of the major autosomes of Drosophila melanogaster.

We constructed a bacterial artificial chromosome (BAC)-based physical map of chromosomes 2 and 3 of Drosophila melanogaster, which constitute 81% of the genome. Sequence tagged site (STS) content, restriction fingerprinting, and polytene chromosome in situ hybridization approaches were integrated to produce a map spanning the euchromatin. Three of five remaining gaps are in repeat-rich regions near the centromeres. A tiling path of clones spanning this map and STS maps of chromosomes X and 4 was sequenced to low coverage; the maps and tiling path sequence were used to support and verify the whole-genome sequence assembly, and tiling path BACs were used as templates in sequence finishing.

Animals↗

An integrated physical and gene map of human distal chromosome 17q24-proximal 17q25 encompassing multiple disease loci.

Genetic mapping studies suggest that a small interval on human chromosome distal 17q24-proximal 17q25 harbors genes involved in sporadic breast and ovarian tumorigenesis and in the autosomal dominant disorders hereditary neuralgic amyotrophy and tylosis with esophageal cancer. Prior to this study, isolated genomic clones and markers were assigned to this interval but integrated physical maps were not available. We improved resolution by isolating 52 additional clones and developing 24 additional markers. Genomic clones spanning distal 17q24-proximal 17q25 were organized into a contig with two gaps that encompassed 14 existing genetic markers, 8 known genes (GALR2, AANAT, ENVL, SFRS2, SEC14L, DNAH17, API4, and TK1), and 11 previously identified expressed sequence tags. This integrated map provides a foundation for identifying additional candidate genes for the disorders mapped to this interval.

Chromosomes, Human, Pair 17↗

Hereditary neuralgic amyotrophy: evidence for genetic homogeneity and mapping to chromosome 17q25.

Hereditary neuralgic amyotrophy (HNA) is a rare autosomal dominant disorder on chromosome 17q, associated with recurrent, episodic, painful brachial plexus neuropathy. Dysmorphic features, including hypotelorism, long nasal bridge and facial asymmetry, are frequently associated with HNA. To assess genetic homogeneity, determine the cytogenetic location, and identify flanking markers for the HNA locus, six pedigrees were studied with multiple DNA markers from distal chromosome 17q. The results in all pedigrees supported linkage of the HNA locus to chromosome 17. A maximum combined lod score (Z = 10.94, theta = 0.05) was obtained with marker D17S939 and the maximum multipoint lod score was 22.768 in the interval defined by D17S802-D17S939. An analysis of crossovers placed the HNA locus within an approximate 4.0-cM interval flanked by D17S1603 and D17S802. Analysis of DNA from a human/mouse somatic cell hybrid with linked markers suggests that band 17q25 harbors the HNA locus. These results support genetic homogeneity within HNA and define a specific interval and a precise cytogenetic location in chromosome 17q25 for this disorder.

Brachial Plexus↗

Prioritization of mental health services in Oregon.

The Oregon Health Plan is an approach to health care reform that increases access to mental health and chemical dependency services. A key feature is the integration of mental and physical health care. The mental health community had to educate policy makers about the importance of mental health and chemical dependency services. They constructed a prioritized list of mental health and chemical dependency services and interdigitated the list with the set of physical health services. The result is a unique attempt to develop a seamless health care system that minimizes discrimination against persons affected by mental illness. The opportunity to achieve parity for mental health must not be delayed or compromised; to do so would worsen the lives of persons already affected by the trauma and stigma associated with mental illness.

Health Care Rationing↗

Ethics and value strategies used in prioritizing mental health services in Oregon.

The authors describe the ethical considerations underlying the inclusion of mental health services into a prioritized health care system. The Oregon Health Plan is a process for defining and delivering basic health services to an entire state. As the plan was developed, the mental health community needed to decide whether or not to participate in the process and, if so, how. Lengthy discussions among mental health consumers, family members, and providers led to a strategy that emphasized the integration of mental health and chemical dependency services into a comprehensive and universal health care program. This approach appears to have achieved relative parity for mental health.

Community Participation↗

Population-based guidelines for performance measurement: a preliminary report.

This paper describes the development of--and early efforts to validate--guidelines that indicate average amounts of service expected to be used by a population of patients with a given disorder who are served by a comprehensive mental health system. These guidelines address expected service use by individuals in 55 diagnostic groups. The purpose of these guidelines is to provide a gauge for evaluating the amounts of service being delivered by managed care organizations. Three population-based guidelines (for attention-deficit/hyperactivity disorder, major depressive disorder, and schizophrenia) are compared to actual amounts of service delivered to enrollees in large behavioral health care systems.

Community Health Planning↗