Showing papers by "David C. Page published in 1994"

A genetic map of the mouse with 4,006 simple sequence length polymorphisms.

Abstract: We have constructed a genetic map of the mouse genome containing 4,006 simple sequence length polymorphims (SSLPs). The map provides an average spacing of 0.35 centiMorgans (cM) between markers, corresponding to about 750 kb. Approximately 90% of the genome lies within 1.1 cM of a marker and 99% lies within 2.2 cM. The markers have an average polymorphism rate of 50% in crosses between laboratory strains. The markers are distributed in a relatively uniform fashion across the genome, although some deviations from randomness can be detected. In particular, there is a significant underrepresentation of markers on the X chromosome. This map represents the two–thirds point toward our goal of developing a mouse genetic map containing 6,000 SSLPs.

Structure and function of ribosomal protein S4 genes on the human and mouse sex chromosomes.

Abstract: The human sex-linked genes RPS4X and RPS4Y encode distinct isoforms of ribosomal protein S4. Insufficient expression of S4 may play a role in the development of Turner syndrome, the complex human phenotype associated with monosomy X. In mice, the S4 protein is encoded by an X-linked gene, Rps4, and is identical to human S4X; there is no mouse Y homolog. We report here the organization of the human RPS4X and RPS4Y and mouse Rps4 genes. Each gene comprises seven exons; the positions of introns are conserved. The 5' flanking sequences of human RPS4X and mouse Rps4 are very similar, while RPS4Y diverges shortly upstream of the transcription start site. In chickens, S4 is encoded by a single gene that is not sex linked. The chicken protein differs from human S4X by four amino acid substitutions, all within a region encoded by a single exon. Three of the four substitutions are also present in human S4Y, suggesting that the chicken S4 gene may have arisen by recombination between S4X- and S4Y-like sequences. Using isoform-specific antisera, we determined that human S4X and S4Y are both present in translationally active ribosomes. S4Y is about 10 to 15% as abundant as S4X in ribosomes from normal male placental tissue and 46,XY cultured cells. In 49,XYYYY cells, S4Y is about half as abundant as S4X. In 49,XXXXY cells, S4Y is barely detectable. These results bear on the hypothesized role of S4 deficiency in Turner syndrome.

Recommendations for Diagnosis, Treatment, and Management of Individuals with Turner Syndrome

Abstract: The objective of this study was to establish the optimum treatment and overall care recommendations for individuals with Turner syndrome at all stages of life as an aid to medical professionals working with these individuals. The Turner's Syndrome Society of the United States brought together 16 nat

Multipoint linkage map of the human pseudoautosomal region, based on single-sperm typing: do double crossovers occur during male meiosis?

Abstract: Sperm typing was used to measure recombination fractions among pseudoautosomal markers and the beginning of the X/Y-specific sequences located at the pseudoautosomal boundary These experiments included primer-extension preamplification and PCR followed by allele typing using gel electrophoresis A newly developed data-analysis program allowed the construction of the first multipoint-linkage sperm-typing map, using results obtained on seven loci from three individuals The large sample size not only confirmed the increased recombination activity of the pseudoautosomal region but allowed an estimate of interference of recombination to be made The coefficient of coincidence was calculated to be 26 over a physical distance of only approximately 1,800 kb The observation of a few sperm presumably resulting from double recombination argues that more than one crossover event can occur in this region during male meiosis

Expression of a mouse Zfy-1/lacZ transgene in the somatic cells of the embryonic gonad and germ cells of the adult testis

Abstract: The Zfy-1 and Zfy-2 genes, which arose by gene duplication, map to the mouse Y chromosome and encode nearly identical zinc-finger proteins. Zfy-1 is expressed in the genital ridge and adult testis and likely encodes a transcription activator. Although potential roles in sex determination and spermatogenesis have been hotly debated, the biological functions of Zfy-1 remain unknown. To study the gene9s regulation, transgenes with 21–28 kb of Zfy-1 5′ flanking DNA placed upstream of lacZ were constructed in plasmids or created by homologous recombination of coinjected DNA molecules. The resulting transgenic mice expressed beta-galactosidase in the genital ridge of both males and females starting between embryonic day 10 and 11 (E10-E11), peaking at E12-E13 and then declining to low levels by E15, a pattern that matches Zfy-1 mRNA as detected by RT-PCR. This lacZ expression in genital ridge was confined to somatic cells as demonstrated by its absence from the alkaline phosphatase-positive germ cells. It had been reported previously that Zfy-1 mRNA was absent from the embryonic gonad of homozygous W(e) embryos, which virtually lack germ cells. By contrast, we observed normal expression of the Zfy-1/lacZ transgene when introduced into the W(e) background, suggesting that germ cells are not necessary for expression. In the adult, the Zfy-1/lacZ transgene is expressed abundantly in developing germ cells. Extragonadal (kidney, meninges, arteries, choroid plexus) expression of the transgene was also observed in embryos. A smaller transgene with only 4.3 kb of Zfy-1 5′ flanking DNA was expressed only in germ cells of adult mice. These results suggest that an enhancer for germ cell expression in the adult lies near the Zfy-1 promoter and that an enhancer for expression in the somatic cells of the embryonic gonad is located further 5′.

Attenuation of monochromatic X-rays by normal and abnormal breast tissues.

Abstract: RATIONALE AND OBJECTIVES. A prior study indicated that differences in the x-ray linear attenuation coefficients of cancerous and normal breast tissues tend to increase as the energy of the incident beam decreases. The authors investigated x-ray energies down to 20 keV. In the current study, the linear attenuation coefficients for normal and selected cancerous breast tissues within the energy range of 14 to 18 keV were determined. METHODS. Fifty breast biopsy specimens consisting of a mixture of breast malignancies, normal tissues, fat specimens, and tumors grown in rats were used. X-ray linear attenuation coefficients were measured for each sample within the energy range of 14.15 to 18 keV, using monoenergetic x-rays from beamline X-19A at the National Synchrotron Light Source at Brookhaven National Laboratory. Each sample was measured at 130 different energies starting at 14.15 keV with step sizes of 0.030 keV. Correlation of the measured attenuation coefficients for cellular makeup was performed. RESULTS. The mean of linear attenuation coefficients for samples classified as “cancers” was 10.9% higher than the mean of samples classified as “normal” breast tissues and was 66.5% higher than the mean of samples classified as normal breast fat. CONCLUSIONS. Differences in the linear attenuation coefficients of monochromatic x-rays between 14.15 and 18 keV do exist between normal and cancerous tissues, but there is some degree of overlap.

Xq-Yq interchange resulting in supernormal X-linked gene expression in severely retarded males with 46,XYq- karyotype.

Abstract: The critical importance of dosage compensation is underscored by a novel human syndrome (“XYXq syndrome”) in which we have detected partial X disomy, demonstrated supernormal gene expression resulting from the absence of X inactivation, and correlated this overexpression with its phenotypic consequences. Studies of three unrelated boys with 46,XYq- karyotypes and anomalous phenotypes (severe mental retardation, generalized hypotonia and microcephaly) show the presence of a small portion of distal Xq on the long arm of the Y derivative. Cells from these boys exhibit twice-normal activity of glucose-6-phosphate dehydrogenase, a representative Xq28 gene product. In all three cases, the presence of Xq DMA on a truncated Y chromosome resulted from an aberrant Xq–Yq interchange occurring in the father's germline.