Enrichment for loci identical-by-descent between pairs of mouse or human genomes by genomic mismatch scanning.

Mapping genes that underlie complex genetic traits, including genes that determine susceptibility to common diseases, requires an efficient method for high-resolution genotyping. Single-nucleotide differences between pairs of allelic sequences from unrelated individuals occur approximately once in every kilobase. Genomic mismatch scanning (GMS), by analyzing numerous single-nucleotide polymorphisms in a single genome-wide step, offers a potentially powerful and efficient approach to linkage analysis. GMS, originally developed in a yeast system, is shown here to be applicable to the more complex mouse and human genomes.

Use of microgenomic technology for analysis of alterations in DNA copy number and gene expression in malignant melanoma.

Chromosome abnormalities in human malignancies have identified the genomic location of several important growth-regulatory genes, including cellular oncogenes and tumour suppressor genes. Melanomas are characterized by recurring chromosome alterations, and it is important to identify those genes whose altered expression may be causally related to melanocytic transformation. This short report presents an overview of strategies used which combine the materials and technologies of the Human Genome Project with clinically directed studies of melanoma biology. The Human Genome Project combines various technologies, including cytogenetic, physical mapping, genetic mapping and DNA sequencing, in order to identify all of the human genes, but especially the 4000 estimated to contribute to human disease. This report focuses first on advances in genome technology that provide information on chromosome rearrangements and DNA copy number changes. This includes a discussion of chromosome microdissection as well as the microexcision of tissue specimens to gain insights into chromosome regions altered in association with melanocyte transformation. Next, there is a brief discussion of the generation and characterization of subtracted cDNA sublibraries which allow the identification of genes uniquely expressed in association with the transformed phenotype of human melanoma cells. Finally, we briefly discuss the feasibility of using a recently developed system for parallel examination of multiple genes based upon robotic printing of cDNAs on glass slides, and simultaneous two-colour fluorescence hybridization to study the expression patterns of cDNAs for their association with melanoma tumour suppression. The combination of these varied molecular technologies may provide insights into previously unrecognized genes involved causally in the pathobiology of this important neoplasm, and may provide new targets for clinical intervention.

Use of a cDNA microarray to analyse gene expression patterns in human cancer.

The development and progression of cancer and the experimental reversal of tumorigenicity are accompanied by complex changes in patterns of gene expression. Microarrays of cDNA provide a powerful tool for studying these complex phenomena. The tumorigenic properties of a human melanoma cell line, UACC-903, can be suppressed by introduction of a normal human chromosome 6, resulting in a reduction of growth rate, restoration of contact inhibition, and suppression of both soft agar clonogenicity and tumorigenicity in nude mice. We used a high density microarray of 1,161 DNA elements to search for differences in gene expression associated with tumour suppression in this system. Fluorescent probes for hybridization were derived from two sources of cellular mRNA [UACC-903 and UACC-903(+6)] which were labelled with different fluors to provide a direct and internally controlled comparison of the mRNA levels corresponding to each arrayed gene. The fluorescence signals representing hybridization to each arrayed gene were analysed to determine the relative abundance in the two samples of mRNAs corresponding to each gene. Previously unrecognized alterations in the expression of specific genes provide leads for further investigation of the genetic basis of the tumorigenic phenotype of these cells.

Fluorescence in situ hybridization: a sensitive method for trisomy 8 detection in bone marrow specimens.

Trisomy 8 is a common anomaly in bone marrow (BM) cells of patients with myeloproliferative disorders (MPD), myelodysplastic syndromes (MDS), or acute nonlymphocytic leukemia (ANLL). We studied the efficacy of fluorescence in situ hybridization (FISH) detection of trisomy 8 in patients with MPD, MDS, or ANLL using directly labeled fluorescent alpha-satellite and whole chromosome paint (WCP) DNA probes specific for chromosome 8. Using FISH, we analyzed interphase nuclei and metaphase spreads from randomized series of BM specimens from normal individuals and patients with varying proportions of trisomy 8 as determined by conventional cytogenetic analysis. The BM of all normal donors contained less than or equal to 2.0% nuclei with 3 interphase FISH signals and less than or equal to 1 metaphase with 3 WCP FISH signals. Ninety-five percent and 98% of BM specimens with at least two metaphase cells with trisomy 8 by cytogenetic analysis contained greater than 2.0% nuclei with 3 interphase FISH and greater than 2 metaphases with 3 WCP FISH signals, respectively. Thirteen patients had 1 in 20 or 1 in 30 metaphase cells with trisomy 8 by conventional cytogenetic studies. Of these patients, four had greater than 2.0% nuclei with 3 interphase FISH signals. The BM of all four patients contained positive metaphase FISH results. We then studied the usefulness of FISH analysis to detect occult trisomy 8 by analyzing BM nuclei from 144 patients who had MPD, MDS, or ANLL and either 20 normal metaphase cells or an abnormal karyotype without trisomy 8. Seven patients had greater than 2.0% nuclei with 3 interphase FISH signals (range, 2.10% to 3.40%) and six patients had 2 or more cells with trisomy 8 upon metaphase FISH or extensive conventional cytogenetic analysis. Our results show that interphase and metaphase FISH analyses are useful methods to detect trisomy 8 cells in BM specimens, especially for specimens with normal or uncertain conventional cytogenetic results.

Sex education in 1900, 1940 and 1980: an historical sketch.

PIP: The changes in coverage and philosophy of sex education in the U.S. from 1900 to 1980 reflect underlying social changes in life and sexual behavior style. Sex education about 1900 was actually antisex and directed toward discouraging sexual behavior and thoughts. The material was presented in an unemotional factual lecture form, sometimes supplemented with approved printed material. By 1940, there was more widespread support for sex education. With the passing of the days of black and white morality, sex education classes took on another purpose, that of helping to contribute to the longterm sexual adjustment of individuals. Segregated classes were still used for presentation of most of material. By 1980, with the advent of more permissive sexual mores, the emphasis of sex education classes has changed to a recognition of the importance of human sexuality to human fulfillment. Open communication is stressed. Mixed-sex classes are used and student discussion is encouraged. There is greater discussion of contraception.^ieng

The school's role in preventing blindness from glaucoma.

A disease which has blinded 50,000 Americans and threatens to blind an additional estimated one million victims who are unaware that they have the disease warrants serious consideration in the health curriculum. That disease, glaucoma, can be neither prevented nor cured. It results when abnormal fluid dynamics within the eye cause increased pressure. The increased pressure can usually be controlled to prevent blindness from occurring. However, prevention of blindness from glaucoma requires early diagnosis and treatment. Since glaucoma is rarely accompanied by pain or warning signs, the best hope for early diagnosis is with regular eye examinations. Health education is the way to teach people the nature and consequences of glaucoma and the role each individual can play in minimizing his or her chances of becoming blind from the disease.