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D R Cox

Publications and source records attributed to D R Cox.

At least 109 records · Page 6Linked to original sources
PubMed1990

Time from infection with HIV to onset of AIDS in patients with haemophilia in the UK.

The two-stage parametric regression model of Brookmeyer and Goedert has been adapted and fitted to data on the development of AIDS in haemophiliacs in the UK who are seropositive for HIV. The risk of developing AIDS by a given time following seroconversion increases with increasing age at seroconversion. It is likely that the risk increases smoothly with age, although the data have been analysed in three age categories, and it is estimated that by seven years after seroconversion 6 per cent of patients aged under 25 at seroconversion, 20 per cent of those aged 25-44 and 34 per cent of those aged 45 or more have developed AIDS. For a given age at seroconversion the annual risk of developing AIDS increases with increasing time after seroconversion, and at seven years the annual risks of developing AIDS during the next year in the three age groups are estimated to be 2 per cent for those aged less than 25 at seroconversion, and 10 and 11 per cent respectively for those aged 25-44 and 45 or more.

Acquired Immunodeficiency Syndrome↗
PubMed1990

A cloned DNA segment from the telomeric region of human chromosome 4p is not detectably rearranged in Huntington disease patients.

Genetic linkage studies have mapped the Huntington disease (HD) mutation to the distal region of the short arm of human chromosome 4. Analysis of recombination events in this region has produced contradictory locations for HD. One possible location is in the region distal to the D4S90 marker, which is located within 300 kilobases of the telomere. Other crossover events predict a more centromeric position for HD. Here we analyze the telomeric region of 4p in detail. Cloned DNA segments were derived from this region by utilizing a radiation-induced somatic cell hybrid as a source of DNA combined with preparative pulsed-field gel electrophoresis to enrich for the telomeric fraction. Additional DNA was obtained by using the cloned segments as multiple start points for cosmid walks. This strategy proved to be an effective method for cloning 250 kilobases of DNA in the region telomeric to D4S90. Hybridization analysis with the cloned DNA did not provide any evidence for the presence of rearrangements of 100 base pairs or greater in the DNA of individuals affected with HD. We also found no change in the size or structure of the 4p telomere in these samples.

Animals↗
PubMed1990

Exon trapping: a genetic screen to identify candidate transcribed sequences in cloned mammalian genomic DNA.

Identification and recovery of transcribed sequences from cloned mammalian genomic DNA remains an important problem in isolating genes on the basis of their chromosomal location. We have developed a strategy that facilitates the recovery of exons from random pieces of cloned genomic DNA. The basis of this "exon trapping" strategy is that, during a retroviral life cycle, genomic sequences of nonviral origin are correctly spliced and may be recovered as a cDNA copy of the introduced segment. By using this genetic assay for cis-acting sequences required for RNA splicing, we have screened approximately 20 kilobase pairs of cloned genomic DNA and have recovered all four predicted exons.

Base Sequence↗
PubMed1990

Structure and variability of human chromosome ends.

Mammalian telomeres are thought to be composed of a tandem array of TTAGGG repeats. To further define the type and arrangement of sequences at the ends of human chromosomes, we developed a direct cloning strategy for telomere-associated DNA. The method involves a telomere enrichment procedure based on the relative lack of restriction endonuclease cutting sites near the ends of human chromosomes. Nineteen (TTAGGG)n-bearing plasmids were isolated, two of which contain additional human sequences proximal to the telomeric repeats. These telomere-flanking sequences detect BAL 31-sensitive loci and thus are located close to chromosome ends. One of the flanking regions is part of a subtelomeric repeat that is present at 10 to 25% of the chromosome ends in the human genome. This sequence is not conserved in rodent DNA and therefore should be a helpful tool for physical characterization of human chromosomes in human-rodent hybrid cell lines; some of the chromosomes that may be analyzed in this manner have been identified, i.e., 7, 16, 17, and 21. The minimal size of the subtelomeric repeat is 4 kilobases (kb); it shows a high frequency of restriction fragment length polymorphisms and undergoes extensive de novo methylation in somatic cells. Distal to the subtelomeric repeat, the chromosomes terminate in a long region (up to 14 kb) that may be entirely composed of TTAGGG repeats. This terminal segment is unusually variable. Although sperm telomeres are 10 to 14 kb long, telomeres in somatic cells are several kilobase pairs shorter and very heterogeneous in length. Additional telomere reduction occurs in primary tumors, indicating that somatic telomeres are unstable and may continuously lose sequences from their termini.

Animals↗
PubMed1989

Epidemiological and statistical aspects of the AIDS epidemic: introduction.

In 1988, a government working party studied estimates of incidence and prevalence of numbers of acquired immunodeficiency syndrome (AIDS) cases. They investigated a series of epidemiological, statistical and mathematical problems associated with predicting trends in incidences of AIDS. This paper introduces a series of papers that give a fuller and more technical exposition of the appendixes of that working party report. The papers provide a brief background to the current state of knowledge on the epidemiology of the infection and the disease; a deterministic model for human immunodeficiency virus (HIV) transmission in the male homosexual community in England and Wales is introduced. Back-projection methods are studied in two papers, following the distribution of the incubation period of the disease. The concept of minimum size of the epidemic is introduced. Mathematical functions to describe the spread of HIV infection are refined by using past trends in the incidence of AIDS to estimate values for some parameters. Survival times for AIDS patients from the point of diagnosis are considered and evidence for changes in male homosexual sexual behaviour is studied; lag-time from the point of diagnosis to the report of the case is also examined. There is a comparative analysis of the AIDS epidemic in various European countries. The incubation period of HIV in patients with haemophilia A and B infections and the problems associated with making predictions for different at-risk groups or small subgroups based on geographical area are discussed. Reasons for fluctuation between the number of reported cases from month to month are provided.

Acquired Immunodeficiency Syndrome↗
PubMed1989

A process of events with notification delay and the forecasting of AIDS.

Analysis and prediction of a point process are studied when there is delay in notifying the occurrence of events. A primarily parametric approach is taken to studying the rate of the underlying process and to predicting future properties of the system. Data on AIDS are used in illustration.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Prediction for small subgroups.

Prediction limits are calculated for the number of events likely to occur in a specified time period in an exponentially growing epidemic. The basis for the prediction is the total number of events observed in the past.

Acquired Immunodeficiency Syndrome↗
PubMed1989

A family of type I keratin genes and the homeobox-2 gene complex are closely linked to the rex locus on mouse chromosome 11.

Type I and type II keratins are major constituents of intermediate filaments that play a fundamental role in the cytoskeletal network. By using both somatic cell hybrids and conventional and interspecific linkage crosses, several genes encoding type I keratins, including the epidermal keratin K10, were shown to be closely linked to the homeobox-2 complex and the rex locus on mouse chromosome 11. The absence of crossovers between type I keratin-encoding genes and rex (N = 239), a locus affecting hair development, raises the possibility that mutations at rex and neighboring loci affecting skin and hair development involve type I keratin genes.

Alleles↗
PubMed1989

Segregation of the Huntington disease region of human chromosome 4 in a somatic cell hybrid.

We have developed an X-irradiation:cell fusion procedure that segregates segments of human chromosomes lacking selectable markers and have used this approach to construct somatic cell hybrids retaining fragments of human chromosome 4 as the only human material. To identify hybrids retaining a small chromosomal fragment in the region of the Huntington disease (HD) gene, we used Southern blot analysis to screen 72 hybrid lines for the presence or absence of seven chromosome 4 single-copy loci. These data, combined with in situ hybridization experiments, identified three hybrids of interest. One of these cell lines, C25, stably retains a 10,000- to 20,000-kb fragment of distal 4p in the vicinity of the HD gene, translocated to a hamster chromosome. Field-inversion gel electrophoresis revealed no evidence of rearrangements in the human DNA present in C25. In combination with similar radiation hybrids, C25 is a valuable tool for isolating DNA probes near the HD gene.

Animals↗
PubMed1989

Isolation and field-inversion gel electrophoresis analysis of DNA markers located close to the Huntington disease gene.

A radiation-induced hybrid cell line containing 10-20 million base pairs of DNA derived from the terminal part of human 4p16 in a background of hamster chromosomes has been used to construct a genomic library highly enriched for human sequences located close to the Huntington disease (HD) gene. Recombinant phage containing human inserts were isolated from this library and used as hybridization probes against two other radiation hybrids containing human fragments with chromosomal breaks in 4p16 and against a human-hamster somatic cell hybrid that retains only the 4p15-4pter part of chromosome 4. Of 121 human phage tested, 6 were mapped distal to the HD-linked D4S10 locus. Since the HD gene is located between D4S10 and the 4p telomere, all of these sequences are likely to be closer to HD than D4S10, and any one of them may be a distal flanking marker for the disease locus. Long-range restriction map analysis performed with a field-inversion gel system shows that the six new loci are distributed in different places within 4p16. Although it is not possible to establish an order for the six sequences with the FIGE data, the results demonstrate that the region detected by these probes must span at least 2000 kb of DNA.

Animals↗
PubMed1989

Attachment of a 40-base-pair G + C-rich sequence (GC-clamp) to genomic DNA fragments by the polymerase chain reaction results in improved detection of single-base changes.

Denaturing gradient gel electrophoresis (DGGE) can be used to distinguish two DNA molecules that differ by as little as a single-base substitution. This method detects approximately 50% of all possible single-base changes in DNA fragments ranging from 50 to approximately 1000 base pairs. To increase the number of single-base changes that can be distinguished by DGGE, we used the polymerase chain reaction to attach a 40-base-pair G + C-rich sequence, designated a GC-clamp, to one end of amplified DNA fragments that encompass regions of the mouse and human beta-globin genes. We show that this GC-clamp allows the detection of mutations, including the hemoglobin sickle (HbS) and hemoglobin C (HbC) mutations within the human beta-globin gene, that were previously indistinguishable by DGGE. In addition to providing an easy way to attach a GC-clamp to genomic DNA fragments, the polymerase chain reaction technique greatly increases the sensitivity of DGGE. With this approach, DNA fragments derived from less than 5 ng of human genomic DNA can be detected by ethidium bromide staining of the gel, obviating the need for radioactive probes. These improvements extend the applicability of DGGE for the detection of polymorphisms and mutations in genomic and cloned DNA.

Animals↗
PubMed1988

The distribution of the incubation period for the acquired immunodeficiency syndrome (AIDS).

This paper contains details of methods and full results of estimates of the incubation period of acquired immunodeficiency syndrome (AIDS) that were outlined in a previous paper by Medley et al. (Nature, Lond. 328, 719 (1987)). The original model is modified to assess the influence of age and sex on the incubation period: age, but not sex, is statistically significant. The difficulties associated with interpretation of these data, and the additional information that would be required to resolve these difficulties are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Gene encoding the beta subunit of S100 protein is on chromosome 21: implications for Down syndrome.

S100 protein is a calcium-binding protein found predominantly in the vertebrate nervous system. Genomic and complementary DNA probes were used in conjunction with a panel of rodent-human somatic cell hybrids to assign the gene for the beta subunit of S100 protein to the distal half of the long arm of human chromosome 21. This gene was identified as a candidate sequence which, when expressed in the trisomic state, may underlie the neurologic disturbances in Down syndrome.

Chromosome Mapping↗
PubMed1988

Human GAP-43: its deduced amino acid sequence and chromosomal localization in mouse and human.

The growth-associated protein (GAP-43) is considered a crucial component of an effective regenerative response in the nervous system. Its phosphorylation by protein kinase C correlates with long-term potentiation. Sequence analysis of human cDNAs coding for this protein shows that the human GAP-43 gene is highly homologous to the rat gene; this homology extends into the 3'-untranslated region. However, the human protein contains a 10 amino acid insert. Somatic cell hybrids demonstrate localization of the GAP-43 gene to human chromosome 3 and to mouse chromosome 16.

Amino Acid Sequence↗
PubMed1988

A functional mouse ornithine decarboxylase gene (Odc) maps to chromosome 12: further evidence of homoeology between mouse chromosome 12 and the short arm of human chromosome 2.

We have used a DNA probe specific for a functional mouse ornithine decarboxylase gene (Odc) in conjunction with a panel of Chinese hamster x mouse somatic cell hybrids to assign Odc to mouse chromosome 12. This assignment provides further evidence of genetic homoeology between a region of mouse chromosome 12 and the distal short arm of human chromosome 2.

Animals↗