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Biomedical subjects

D R Cox

Publications and source records attributed to D R Cox.

At least 55 records · Page 3Linked to original sources
PubMed1999

Longitudinal study of nutrient and food intakes of white preschool children aged 24 to 60 months.

OBJECTIVE: To determine nutrient and food intakes of 72 white preschool children primarily from families of middle and upper socioeconomic status and to compare children's nutrient intakes with current recommendations. DESIGN: Six in-home interviews were conducted with mothers when children were 24 to 60 months old; at each time mothers provided 3 days of dietary information on the child. Children and mothers independently provided information on the child's favorite and least favorite foods at 42 and 54 months. SUBJECTS: Preschool children (24 to 60 months old) participating in a longitudinal study. STATISTICAL ANALYSES: Mean nutrient intakes were compared with the most recent Recommended Dietary Allowances/Adequate Intakes. Differences over time were tested with repeated-measures analysis of variance; gender differences were determined with t tests. Food frequencies (i.e., percentage of children consuming specific foods) were determined from dietary recalls and food records. Dietary variety was assessed with the Variety Index for Toddlers or the Variety Index for Children. RESULTS: Means were consistently less than the RDA/AI for energy, zinc, folate, and vitamins D and E. Energy, carbohydrate, and fat intakes were highest (P < or = .01) at 60 months. Boys consumed more (P < or = .05) protein (10 g), calcium (197 mg), magnesium (35 mg), and pantothenic acid (0.8 mg) at 60 months than did girls. Foods most commonly eaten were fruit drink, carbonated beverages, 2% milk, and french fries. The vegetable group consistently had the lowest variety scores; vegetables also dominated least favorite foods lists. APPLICATIONS: Parents need to be encouraged to include more sources of zinc, folate, vitamin E, and vitamin D in children's diets. Parents should also encourage their children to eat more vegetables, zinc- and folate-fortified cereals, lean red meats, seafood, vegetable oils, and low-fat milk.

Adult↗
PubMed1998

A physical map of 30,000 human genes.

A map of 30,181 human gene-based markers was assembled and integrated with the current genetic map by radiation hybrid mapping. The new gene map contains nearly twice as many genes as the previous release, includes most genes that encode proteins of known function, and is twofold to threefold more accurate than the previous version. A redesigned, more informative and functional World Wide Web site (www.ncbi.nlm.nih.gov/genemap) provides the mapping information and associated data and annotations. This resource constitutes an important infrastructure and tool for the study of complex genetic traits, the positional cloning of disease genes, the cross-referencing of mammalian genomes, and validated human transcribed sequences for large-scale studies of gene expression.

Animals↗
PubMed1998

Some aspects of measurement error in explanatory variables for continuous and binary regression models.

A simple form of measurement error model for explanatory variables is studied incorporating classical and Berkson cases as particular forms, and allowing for either additive or multiplicative errors. The work is motivated by epidemiological problems, and therefore consideration is given not only to continuous response variables but also to logistic regression models. The possibility that different individuals in a study have errors of different types is also considered. The relatively simple estimation procedures proposed for use with cohort data and case-control data are checked by simulation, under the assumption of various error structures. The results show that even in situations where conventional analysis yields slope estimates that are on average attenuated by a factor of approximately 50 per cent, estimates obtained using the proposed amended likelihood functions are within 5 per cent of their true values. The work was carried out to provide a method for the analysis of lung cancer risk following residential radon exposure, but it should be applicable to a wide variety of situations.

Adolescent↗
PubMed1997

A Food Variety Index for Toddlers (VIT): development and application.

OBJECTIVE: To develop a variety index based on the Food Guide Pyramid that is specific to toddlers and is indicative of dietary adequacy. DESIGN: Subjects' mothers were assigned randomly to two in-home interviews with a registered dietitian at four possible collection periods: 24, 28, 32, or 36 months. Three days of dietary information were collected at each period. A Variety Index for Toddlers (VIT) was developed to assess variety within and among food groups based on the number of servings from the food groups in the Food Guide Pyramid. SUBJECTS: White children aged 24 to 36 months (n = 124) and their mothers who were participants in an ongoing longitudinal study. STATISTICAL ANALYSES: Descriptive statistical procedures were performed on VIT scores. Mean adequacy ratio (MAR) scores were calculated for all subjects and compared with VIT scores. RESULTS: Bread group scores were consistently the highest of the individual food groups (mean score = 0.94 to 0.96 on the 0.0 to 1.0 scale); the vegetable and meat groups were generally the lowest (mean score = 0.68 to 0.73 and 0.73 to 0.76, respectively). Mean VIT scores (an average of the five food group scores) over the four collection periods ranged from 0.79 +/- 0.14 to 0.81 +/- 0.15; a score of 1.00 represented intake of at least the minimum number of recommended servings from each food group. VIT scores were strongly correlated to the MAR score of nutrient adequacy (r = +.74, P < .01). APPLICATIONS: The VIT can provide a numeric description of dietary variety specific to toddlers. VIT scores can be compared with other characteristics of children, and this index has the potential to be adapted for use with other age groups and populations.

Adult↗
PubMed1997

An STS-based radiation hybrid map of the human genome.

We have constructed a physical map of the human genome by using a panel of 83 whole genome radiation hybrids (the Stanford G3 panel) in conjunction with 10,478 sequence-tagged sites (STSs) derived from random genomic DNA sequences, previously mapped genetic markers, and expressed sequences. Of these STSs, 5049 are framework markers that fall into 1766 high-confidence bins. An additional 945 STSs are indistinguishable in their map location from one or more of the framework markers. These 5994 mapped STSs have an average spacing of 500 kb. An additional 4484 STSs are positioned with respect to the framework markers. Comparison of the orders of markers on this map with orders derived from independent meiotic and YAC STS-content maps indicates that the error rate in defining high-confidence bins is < 5%. Analysis of 322 random cDNAs indicates that the map covers the vast majority of the human genome. This STS-based radiation hybrid map of the human genome brings us one step closer to the goal of a physical map containing 30,000 unique ordered landmarks with an average marker spacing of 100 kb.

Animals↗
PubMed1996

A gene map of the human genome.

The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at http://www.ncbi.nlm.nih.gov/SCIENCE96/.

Amino Acid Sequence↗
PubMed1996

Human homolog of patched, a candidate gene for the basal cell nevus syndrome.

The basal cell nevus syndrome (BCNS) is characterized by developmental abnormalities and by the postnatal occurrence of cancers, especially basal cell carcinomas (BCCs), the most common human cancer. Heritable mutations in BCNS patients and a somatic mutation in a sporadic BCC were identified in a human homolog of the Drosophila patched (ptc) gene. The ptc gene encodes a transmembrane protein that in Drosophila acts in opposition to the Hedgehog signaling protein, controlling cell fates, patterning, and growth in numerous tissues. The human PTC gene appears to be crucial for proper embryonic development and for tumor suppression.

Adult↗
PubMed1996

Mutations in the gene encoding cystatin B in progressive myoclonus epilepsy (EPM1)

Progressive myoclonus epilepsy of the Unverricht-Lundborg type (EPM1) is an autosomal recessive inherited form of epilepsy, previously linked to human chromosome 21q22.3. The gene encoding cystatin B was shown to be localized to this region, and levels of messenger RNA encoded by this gene were found to be decreased in cells from affected individuals. Two mutations, a 3' splice site mutation and a stop codon mutation, were identified in the gene encoding cystatin B in EPM1 patients but were not present in unaffected individuals. These results provide evidence that mutations in the gene encoding cystatin B are responsible for the primary defect in patients with EPM1.

Amino Acid Sequence↗
PubMed1996

Functional effects of the mouse weaver mutation on G protein-gated inwardly rectifying K+ channels.

The weaver mutation corresponds to a substitution of glycine to serine in the H5 region of a G protein-gated inwardly rectifying K+ channel gene (GIRK2). By studying mutant GIRK2 weaver homomultimeric channels and heteromultimeric channels comprised of GIRK2 weaver and GIRK1 in Xenopus oocytes, we found that GIRK2 weaver homomultimeric channels lose their selectivity for K+ ions, giving rise to inappropriate receptor-activated and basally active Na+ currents, whereas heteromultimers of GIRK2 weaver and GIRK1 appeared to have reduced current. Immunohistochemical localization indicates that GIRK2 and GIRK1 proteins are expressed in the cerebellar neurons of mice at postnatal day 4, at a time when these neurons normally undergo differentiation. Thus, the aberrant behavior of mutant GIRK2 weaver channels could affect the development of weaver mice in at least two distinct ways.

Aging↗
PubMed1996

Construction of a 750-kb bacterial clone contig and restriction map in the region of human chromosome 21 containing the progressive myoclonus epilepsy gene.

The gene responsible for progressive myoclonus epilepsy of the Unverricht-Lundborg type (EPM1) is located on human chromosome 21q22.3 in a region defined by recombination breakpoints and linkage disequilibrium. As part of an effort to clone the EPM1 gene on the basis of its chromosomal location, we have constructed a 753-kb bacterial clone contig that encompasses the region containing the gene. Because DNA markers from the region did not identify intact yeast artificial chromosome (YAC) clones after screening several libraries, we built the contig from cosmid clones and used bacterial artificial chromosome (BAC) and bacteriophage P1 clones to fill gaps. In addition to constructing the clone contig, we determined the locations of the EcoRI, SacII, EagI, and NotI restriction sites in the clones, resulting in a high-resolution restriction map of the region. Most of the contig is represented by a level of redundancy that allows the orders of most restriction sites to be determined, provides multiple data points supporting the clone orders and orientations, and allows a set of clones with a minimum degree of overlap to be chosen for efficient additional analysis. The clone and restriction maps are in excellent agreement with maps generated of the region by other methods. These ordered bacterial clones and the mapping information obtained from them provide valuable reagents for isolating candidate genes for EPM1, as well as for determining the nucleotide sequence of a 750 kb region of the human genome.

Base Sequence↗
PubMed1996

Progressive myoclonus epilepsy EPM1 locus maps to a 175-kb interval in distal 21q.

The EPM1 locus responsible for progressive myoclonus epilepsy of Unverricht-Lundborg type (MIM 254800) maps to a region in distal chromosome 21q where positional cloning has been hampered by the lack of physical and genetic mapping resolution. We here report the use of a recently constituted contig of cosmid, BAC, and P1 clones that allowed new polymorphic markers to be positioned. These were typed in 53 unrelated disease families from an isolated Finnish population in which a putative single ancestral EPM1 mutation has segregated for an estimated 100 generations. By thus exploiting historical recombinations in haplotype analysis, EPM1 could be assigned to the approximately 175-kb interval between the markers D21S2040 and D21S1259.

Adult↗
PubMed1996

Selected locus and multiple panel models for radiation hybrid mapping.

We develop two new types of models for whole-genome radiation hybrid mapping using the general multipoint framework. The first, selected locus models, are appropriate for mapping markers in the region of a selectable locus that was used in creation of the hybrids. The models allow for strong retention of the selectable locus, with retention rates decreasing with increasing distance from the selectable locus in both directions. We illustrate the application of these models with 10 chromosome 17 sequence-tagged site (STS) markers and the thymidine kinase (TK) locus typed on a whole-genome hybrid panel in which TK was used in the selection process. The second set of models are appropriate when loci typed on two or more independent panels are to be used to build maps. Maps can be built assuming interlocus distances are independent or proportional between the panels, and the hypothesis of proportional distances can be tested. We illustrate the application of these models by using 27 chromosome 21 STS markers typed on two hybrid panels created with radiation doses of approximately 10,000 and approximately 50,000 Rads.

Chromosome Mapping↗
PubMed1995

A potassium channel mutation in weaver mice implicates membrane excitability in granule cell differentiation.

Early events in neuronal differentiation are generally considered to be regulated by factors independent of alterations in membrane permeability. Weaver mice harbour a mutation that blocks neuronal differentiation just after cessation of cell division, prior to cell migration and synaptogenesis. Cerebellar granule cells in homozygous weaver mice fail to differentiate, either because intrinsic cues are absent or because the granule cells are unable to respond to those cues. We now report that weaver mice have a missense mutation in a gene encoding a G-protein coupled inward rectifier potassium channel. The mutation alters the putative ion-permeable, pore-forming domain of the protein, suggesting that granule cell differentiation is regulated by changes in membrane permeability.

Amino Acid Sequence↗
PubMed1995

A yeast assay for functional detection of mutations in the human cystathionine beta-synthase gene.

Mutations in the human cystathionine beta-synthase (CBS) gene are known to cause homocystinuria and may also be a significant risk factor for premature atherosclerosis. We have previously shown that the human CBS protein can substitute for the endogenous yeast CBS protein in Saccharomyces cerevisiae. We now show that expression of three different CBS mutants known to be associated with reduced enzyme activity in humans fail to complement growth in the yeast assay. In addition, we have used the yeast CBS assay to identify eight mutant CBS alleles in cell lines from patients with CBS deficiency. These mutant alleles include two previously identified and five novel CBS mutations. Our results also demonstrate that the yeast CBS assay can detect a large percentage of individuals heterozygous for mutations in CBS. This system should be useful in determining the relationship between CBS mutations and human disease.

Alleles↗
PubMed1995

Statistical methods for polyploid radiation hybrid mapping.

Radiation hybrid mapping is a somatic cell technique for ordering genetic loci along a chromosome and estimating physical distances between adjacent loci. This paper presents a model of fragment generation and retention for data involving two or more copies of the chromosome of interest per clone. Such polyploid data can be generated by initially irradiating normal diploid cells or by pooling haploid or diploid clones. The current model assumes that fragments are generated in the ancestral cell of a clone according to an independent Poisson breakage process along each chromosome. Once generated, fragments are independently retained in the clone with a common retention probability. On the basis of this and less restrictive retention models, statistical criteria such as minimum obligate breaks, maximum likelihood ratios, and Bayesian posterior probabilities can be used to decide locus order. Distances can be estimated by maximum likelihood. Likelihood computation is particularly challenging, and computing techniques from the theory of hidden Markov chains prove crucial. Within this context it is possible to incorporate typing errors. The statistical tools discussed here are applied to 14 loci on the short arm of human chromosome 4.

Chromosome Mapping↗