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Biomedical subjects

P J de Jong

Publications and source records attributed to P J de Jong.

At least 19 recordsLinked to original sources

Do health care providers' attitudes towards back pain predict their treatment recommendations? Differential predictive validity of implicit and explicit attitude measures.

The current study aimed to measure the differential predictive value of implicit and explicit attitude measures on treatment behaviour of health care providers. Thirty-six physiotherapy students completed a measure of explicit treatment attitude (Pain Attitudes And Beliefs Scale For Physiotherapists-PABS-PT) and a measure of implicit treatment attitude (Extrinsic Affective Simon Task-EAST). Furthermore, they gave treatment recommendations for a patient simulating back pain on three video scenes. The implicit and explicit measures of attitudes were only weakly related to each other. However, both were differentially related to treatment recommendations. The implications of the differential predictive value of implicit and explicit attitude measures for treatment behaviour are discussed.

Adult↗

Using a pericentromeric interspersed repeat to recapitulate the phylogeny and expansion of human centromeric segmental duplications.

Despite considerable advances in sequencing of the human genome over the past few years, the organization and evolution of human pericentromeric regions have been difficult to resolve. This is due, in part, to the presence of large, complex blocks of duplicated genomic sequence at the boundary between centromeric satellite and unique euchromatic DNA. Here, we report the identification and characterization of an approximately 49-kb repeat sequence that exists in more than 40 copies within the human genome. This repeat is specific to highly duplicated pericentromeric regions with multiple copies distributed in an interspersed fashion among a subset of human chromosomes. Using this interspersed repeat (termed PIR4) as a marker of pericentromeric DNA, we recovered and sequence-tagged 3 Mb of pericentromeric DNA from a variety of human chromosomes as well as nonhuman primate genomes. A global evolutionary reconstruction of the dispersal of PIR4 sequence and analysis of flanking sequence supports a model in which pericentromeric duplications initiated before the separation of the great ape species (>12 MYA). Further, analyses of this duplication and associated flanking duplications narrow the major burst of pericentromeric duplication activity to a time just before the divergence of the African great ape and human species (5 to 7 MYA). These recent duplication exchange events substantially restructured the pericentromeric regions of hominoid chromosomes and created an architecture where large blocks of sequence are shared among nonhomologous chromosomes. This report provides the first global view of the series of historical events that have reshaped human pericentromeric regions over recent evolutionary time.

Animals↗

A comparative map of bovine chromosome 19 based on a combination of mapping on a bacterial artificial chromosome scaffold map, a whole genome radiation hybrid panel and the human draft sequence.

We have constructed a medium density physical map of bovine chromosome 19 using a combination of mapping loci on both a bovine bacterial artificial chromosome (BAC) scaffold map and a whole genome radiation hybrid (WGRH) panel. The resulting map contains 70 loci spanning the length of bovine chromosome 19. Three contiguous groups of BACs were identified on the basis of multiple loci mapping to individual BAC clones. Bovine chromosome 19 was found in this study to be comprised almost entirely from regions of human chromosome 17, with a small region putatively assigned to human chromosome 10. Fourteen breakpoints between the bovine and human chromosomes were detected, with a possibility of five more based on ordering of the WGRH map.

Animals↗

A physical map of the human genome.

The human genome is by far the largest genome to be sequenced, and its size and complexity present many challenges for sequence assembly. The International Human Genome Sequencing Consortium constructed a map of the whole genome to enable the selection of clones for sequencing and for the accurate assembly of the genome sequence. Here we report the construction of the whole-genome bacterial artificial chromosome (BAC) map and its integration with previous landmark maps and information from mapping efforts focused on specific chromosomal regions. We also describe the integration of sequence data with the map.

Chromosomes, Artificial, Bacterial↗

The physical maps for sequencing human chromosomes 1, 6, 9, 10, 13, 20 and X.

We constructed maps for eight chromosomes (1, 6, 9, 10, 13, 20, X and (previously) 22), representing one-third of the genome, by building landmark maps, isolating bacterial clones and assembling contigs. By this approach, we could establish the long-range organization of the maps early in the project, and all contig extension, gap closure and problem-solving was simplified by containment within local regions. The maps currently represent more than 94% of the euchromatic (gene-containing) regions of these chromosomes in 176 contigs, and contain 96% of the chromosome-specific markers in the human gene map. By measuring the remaining gaps, we can assess chromosome length and coverage in sequenced clones.

Chromosomes, Human, Pair 1↗

Integration of cytogenetic landmarks into the draft sequence of the human genome.

We have placed 7,600 cytogenetically defined landmarks on the draft sequence of the human genome to help with the characterization of genes altered by gross chromosomal aberrations that cause human disease. The landmarks are large-insert clones mapped to chromosome bands by fluorescence in situ hybridization. Each clone contains a sequence tag that is positioned on the genomic sequence. This genome-wide set of sequence-anchored clones allows structural and functional analyses of the genome. This resource represents the first comprehensive integration of cytogenetic, radiation hybrid, linkage and sequence maps of the human genome; provides an independent validation of the sequence map and framework for contig order and orientation; surveys the genome for large-scale duplications, which are likely to require special attention during sequence assembly; and allows a stringent assessment of sequence differences between the dark and light bands of chromosomes. It also provides insight into large-scale chromatin structure and the evolution of chromosomes and gene families and will accelerate our understanding of the molecular bases of human disease and cancer.

Chromosome Aberrations↗

Comparative feline genomics: a BAC/PAC contig map of the major histocompatibility complex class II region.

The genome organization of the human major histocompatibility complex (MHC) will be best understood in a comparative evolutionary context. We describe here the construction of a physical map for the feline MHC. A large-insert domestic cat genomic DNA library was developed using a P1 artificial chromosome (PAC) with a genomic representation of 2.5x and an average insert size of 80 kb. A sequence-ready 660-kb bacterial artificial chromosome/PAC contig map of the domestic cat MHC class II region was constructed with a gene order similar to, but distinct from, that of human and mice: DPB/DPA, Ring3, DMB, TAP1, DOB, DRB2, DRA3, DRB1, DRA2, and DRA1. Fluorescence in situ hybridization analyses of selected class II PAC clones confirmed that the class II region lies in the pericentromeric region of cat chromosome B2. However, apparently unlike the human and mouse MHCs, the domestic cat DRA and DRB genes have undergone multiple duplications and the DQ region has been deleted.

Animals↗

Source and component genes of a 6-200 Mb gene cluster in the house mouse.

We identified and analyzed the genes Sp100, Csprs, and Ifi75 in two members of the genus Mus, M. musculus and M. caroli. Sp100 is a nuclear dot gene; Csprs and Ifi75 are novel genes encoding a putative G-protein coupled receptor (GPCR) and a putative transcriptional coactivator, respectively. A fourth gene, Sp100-rs, occurs in M. musculus, but not in M. caroli. Sp100-rs is a chimeric gene which arose by fusion of Sp100 and Csprs copies. Sp100-rs and Ifi75 are components of a repeat cluster that extends over 6-200 Mb of the M. musculus genome. The Sp100-rs fusion gene arose only 1-2 million years ago and has become fixed and amplified in M. musculus. Although the gene is transcribed, it appears to have no function. The repeat cluster may have become fixed in the species as a 'hitchhiker' in a 'selective sweep'.

Animals↗

A reaction time paradigm to assess (implicit) complaint-specific dysfunctional beliefs.

We investigated whether an implicit association test (IAT) can be used to assess dysfunctional beliefs in the realm of psychopathology. As a first exploration we therefore constructed a IAT that was designed to differentiate between high and low social anxious individuals. Social situation and neutral words were the targets (e.g. date vs hall), and positive and negative outcomes (e.g. compliment vs rejection) the associated attributes. High social anxious women (N=32) showed the predicted deterioration of task performance if the required responses switched from compatible to incompatible with the idea that social situations are related to negative outcomes and vice versa, whereas the opposite was true for low anxious women (N=32). Thus a modified IAT seems a useful and highly flexible tool to implicitly assess complaint-specific dysfunctional associations and may be a valuable addition to the usual (explicit) self-report measures of patients' beliefs.

Adolescent↗

Positional cloning of the mouse saccharin preference (Sac) locus.

Differences in sweetener intake among inbred strains of mice are partially determined by allelic variation of the saccharin preference (Sac) locus. Genetic and physical mapping limited a critical genomic interval containing Sac to a 194 kb DNA fragment. Sequencing and annotation of this region identified a gene (Tas1r3) encoding the third member of the T1R family of putative taste receptors, T1R3. Introgression by serial backcrossing of the 194 kb chromosomal fragment containing the Tas1r3 allele from the high-sweetener-preferring C57BL/6ByJ strain onto the genetic background of the low-sweetener-preferring 129P3/J strain rescued its low-sweetener-preference phenotype. Polymorphisms of Tas1r3 that are likely to have functional significance were identified using analysis of genomic sequences and sweetener-preference phenotypes of genealogically distant mouse strains. Tas1r3 has two common haplotypes, consisting of six single nucleotide polymorphisms: one haplotype was found in mouse strains with elevated sweetener preference and the other in strains relatively indifferent to sweeteners. This study provides compelling evidence that Tas1r3 is equivalent to the Sac locus and that the T1R3 receptor responds to sweeteners.

Alleles↗

A bacterial artificial chromosome library for sequencing the complete human genome.

A 30-fold redundant human bacterial artificial chromosome (BAC) library with a large average insert size (178 kb) has been constructed to provide the intermediate substrate for the international genome sequencing effort. The DNA was obtained from a single anonymous volunteer, whose identity was protected through a double-blind donor selection protocol. DNA fragments were generated by partial digestion with EcoRI (library segments 1--4: 24-fold) and MboI (segment 5: sixfold) and cloned into the pBACe3.6 and pTARBAC1 vectors, respectively. The quality of the library was assessed by extensive analysis of 169 clones for rearrangements and artifacts. Eighteen BACs (11%) revealed minor insert rearrangements, and none was chimeric. This BAC library, designated as "RPCI-11," has been used widely as the central resource for insert-end sequencing, clone fingerprinting, high-throughput sequence analysis and as a source of mapped clones for diagnostic and functional studies.

Chromosomes, Artificial, Bacterial↗

Modular bacterial artificial chromosome vectors for transfer of large inserts into mammalian cells.

To facilitate the use of large-insert bacterial clones for functional analysis, we have constructed new bacterial artificial chromosome vectors, pPAC4 and pBACe4. These vectors contain two genetic elements that enable stable maintenance of the clones in mammalian cells: (1) The Epstein-Barr virus replicon, oriP, is included to ensure stable episomal propagation of the large insert clones upon transfection into mammalian cells. (2) The blasticidin deaminase gene is placed in a eukaryotic expression cassette to enable selection for the desired mammalian clones by using the nucleoside antibiotic blasticidin. Sequences important to select for loxP-specific genome targeting in mammalian chromosomes are also present. In addition, we demonstrate that the attTn7 sequence present on the vectors permits specific addition of selected features to the library clones. Unique sites have also been included in the vector to enable linearization of the large-insert clones, e. g., for optical mapping studies. The pPAC4 vector has been used to generate libraries from the human, mouse, and rat genomes. We believe that clones from these libraries would serve as an important reagent in functional experiments, including the identification or validation of candidate disease genes, by transferring a particular clone containing the relevant wildtype gene into mutant cells or transgenic or knock-out animals.

Animals↗

The t(14;21)(q11.2;q22) chromosomal translocation associated with T-cell acute lymphoblastic leukemia activates the BHLHB1 gene.

We have cloned the genomic breakpoints for a balanced t(14;21)(q11. 2;q22) chromosomal translocation associated with T-cell acute lymphoblastic leukemia. Sequence analysis of the genomic breakpoints indicated that the translocation had been mediated by an illegitimate V(D)J recombination event that disrupted the T-cell receptor (TCR) alpha locus and placed the TCR alpha locus enhancer on the derivative 21 chromosome. We identified a previously unreported transcript, designated BHLHB1 (for basic domain, helix-loop-helix protein, class B, 1) that had been activated by the translocation. BHLHB1 mapped to the region of chromosome 21 that has been proposed to be responsible, at least in part, for the learning deficits seen in children with Down's syndrome. Although BHLHB1 expression normally is restricted to neural tissues, T-cell lymphoblasts with the t(14;21)(q11.2;q22) also expressed high levels of BHLHB1 mRNA. Expression of BHLHB1 dramatically inhibited E2A-mediated transcription activation in NIH 3T3 fibroblasts and Jurkat T cells. This observation suggests that BHLHB1, similar to SCL/TAL1, may exert a leukemogenic effect through a functional inactivation of E2A or related proteins.

Amino Acid Sequence↗

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↗

If you suffer from a headache, then you have a brain tumour: domain-specific reasoning 'bias' and hypochondriasis.

We explored whether hypochondriacal patients selectively search for threat-confirming information when asked to judge the validity of conditional rules in the context of general and health threats. We also explored several factors that may underly participants' information selection (e.g., believability of the rule). Hypochondriacal patients (n = 20) and healthy controls (n = 20) were presented with modified Wason Selection Tasks (WSTs). The WSTs contained safety rules and danger rules. In the context of general threat, both groups of participants adopted a verificationistic strategy in the case of danger rules and a Popperian strategy in the case of safety rules. Importantly, only hypochondriacal persons showed a similar threat-confirming reasoning pattern in the context of health threat. The latter finding contrasts with the earlier study of de Jong et al. (1998) [de Jong, P. J., Haenen, M.-A., Schmidt, A., & Mayer, B. (1998a). Hypochondriasis: the role of fear-confirming reasoning. Behaviour Research and Therapy, 36, 65-74; de Jong, P. J., Mayer, B., van der Hijden, B., Bögels, S., & van den Hout, M. (1998b). Better safe than sorry: reasoning with conditionals in the context of threat. Submitted for publication.] in which both hypochondriacs and healthy controls showed a threat-confirming strategy in the domain of health threat. The WSTs in that study however, contained a (unintended) worry manipulation ("after hearing this, you get worried"), which might have induced a reasoning strategy in controls that is normally restricted to hypochondriacs. Taken together, the present results sustain the idea that the perception of threat activates a better safe than sorry strategy. In the case of phobic threats, such a reasoning strategy immunizes against refutation of phobic convictions.

Adult↗