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P C Watkins

Publications and source records attributed to P C Watkins.

At least 19 recordsLinked to original sources
PubMed2000

Unconscious memory bias in depression: perceptual and conceptual processes.

Mood-congruent memory (MCM) bias in depression was investigated using 4 different implicit memory tests. Two of the implicit tests were perceptually driven, and 2 were conceptually driven. Depressed participants and nondepressed controls were assigned to 1 of 4 implicit memory tests after studying positive and negative adjectives. Results showed no MCM bias in the perceptually driven tests. MCM was demonstrated in 1 of the conceptually driven tests, but only for adjectives that were conceptually encoded. Results support the theory that mood-congruent processes in depression are limited to conceptual processing. However, activation of conceptual processes may not be sufficient for demonstrating mood congruency.

Adult↗
PubMed1996

Unconscious mood-congruent memory bias in depression.

The purpose of this study was to investigate an unconscious or implicit mood-congruent memory (MCM) bias in clinical depression. Many studies have shown an explicit memory bias, but no study has yet found an implicit MCM bias in clinical depression. The authors compared depressed and control group participants on a conceptually driven implicit memory test. After studying words of positive, neutral, and negative affective valences, participants produced free associations to various cues. Implicit memory or priming was demonstrated by the production of more studied than unstudied words to the association cues. Depressed participants showed more priming of negative words, whereas controls showed more priming of positive words, thus supporting the MCM pattern. Also, no implicit memory deficit was found in depressed participants. These findings are discussed in the context of several prominent theories of cognition and depression.

Adolescent↗
PubMed1994

AML1 fusion transcripts in t(3;21) positive leukemia: evidence of molecular heterogeneity and usage of splicing sites frequently involved in the generation of normal AML1 transcripts.

The t(3;21)(q26;q22) is associated with chronic myelogenous leukemia in blast crisis (CML-BC), leukemia evolving from (therapy-related) myelodysplasia, and with leukemia following other hematopoietic proliferative diseases. Molecular cytogenetic analysis and cloning of a few t(3;21) cases indicate that the breakpoints are quite heterogeneous even within a specific clinical phenotype. Interestingly some of the (3;21) breakpoints involve the AML1 gene previously found rearranged in the t(8;21) associated with acute myelogenous leukemia. AML1 is related to the Drosophila gene runt and is the human counterpart of the gene for the alpha subunit of the nuclear polyoma enhancer binding protein (PEBP2) also known as the core binding factor (CBF). In the t(3;21) AML1 was found rearranged with EAP, a gene on chromosome 3 encoding a small ribosomal protein, as well as with EV11, another gene on chromosome 3. Here we report our study of six cases of t(3;21). By using fluorescence in situ hybridization (FISH) analysis and AML1 probes we could conclude that at least in two CML-BC cases the breakpoint occurred in the AML1 intron that is disrupted by the t(8;21). An AML1/EAP fusion transcript, different from the one described in a therapy-related myelodysplasia, was detected in both CML-BC cases. This transcript is expected to result in a predicted protein containing the AML1 nuclear binding domain with an attached stretch of 17 amino acids unrelated to the EAP small ribosomal protein. In the other t(3;21) patients we could not detect an AML1/EAP transcript or an AML1/EV11 transcript. This result suggests heterogeneity of the t(3;21) at the molecular level. The AML1 chimeric transcripts identified so far, both in the t(3;21) and in the t(8;21), diverge from the normal transcripts either after exon 5 or exon 6. Here we show that in normal AML1 transcripts different splicing events are seen to occur after AML1 exon 5 as well as exon 6.

Amino Acid Sequence↗
PubMed1993

The exon trapping assay partly discriminates against alternatively spliced exons.

A cosmid containing eight exons of the gene coding for the microtubule-associated tau protein was subjected to the exon trapping assay. All the constitutive exons contained in the cosmid (4, 5, 7 and 9) were efficiently captured regardless of size. Of the four alternatively spliced exons, three (3, 4A and 8) were not isolated by the assay, but the behavior of exon 6 depended on the identity of its flanking exons.

Alternative Splicing↗
PubMed1992

Transcriptionally active chimeric gene derived from the fusion of the AML1 gene and a novel gene on chromosome 8 in t(8;21) leukemic cells.

In the t(8;21)(q22;q22) of acute myelogenous leukemia (AML), the breakpoint on chromosome 21 disrupts the AML1 gene, generally in the intron between exons 5 and 6. To isolate fusion transcripts of AML1, and an as yet unidentified gene on chromosome 8 involved in the rearrangement, we used rapid amplification of cDNA ends (RACE) and primers for AML1 exons 5 and 6. A fusion transcript was identified by 3' RACE in the RNA of t(8;21) leukemic cells that also express multiple normal AML1 transcripts. This result clearly indicates that at least one transcriptionally active chimeric gene is generated by the chromosome translocation. This gene on the 8q- derivative represents the fusion between the 5' portion of the AML1 gene with the 3' portion of a chromosome 8 gene that contains a region of sequence homology with the cyclin D2 gene, here referred to as the CDR gene (cyclin D-related gene). The chimeric gene is probably responsible for the pathogenesis of the 8;21 AML. This finding makes it possible to detect the translocation at the molecular level, thus improving the diagnosis and monitoring of the disease in leukemic patients.

Base Sequence↗
PubMed1992

Generation of 19 STS markers that can be anchored at specific sites on human chromosome 21.

Sequence-tagged sites (STSs) are short stretches of DNA that can be specifically detected by the polymerase chain reaction (PCR) and can be used to construct long-range physical maps of chromosomal DNA. These STSs can be detected by PCR assays developed by reference to data obtained from the sequencing of restriction fragment length polymorphism-DNA markers for chromosome 21, which were derived from recombinant lamba-phage and plasmid clones made from DNA of a human-hamster hybrid cell line. In this report, we describe the generation of 19 new STSs that are specific for human chromosome 21.

Base Sequence↗
PubMed1992

Mood-congruent memory in depression: emotional priming or elaboration?

We investigated whether mood-congruent memory (MCM) bias in depression is a function of implicit or explicit memory. Implicit memory is taken as a measure of ease of activation, whereas explicit memory also taps elaboration. As expected, MCM bias was found in the explicit memory task but not in the implicit memory task. We believe this finding supports the involvement of elaborative mechanisms in MCM. In addition, memory bias was found with words related to depression but not with words denoting physical threat. Thus, the MCM bias in explicit memory was found to be specific to information that was congruent with depression rather than to all negative information.

Adult↗
PubMed1992

A genetic linkage map of human chromosome 21: analysis of recombination as a function of sex and age.

A genetic linkage map of human chromosome 21 has been constructed using 22 anonymous DNA markers and five complementary DNAs (cDNAs) encoding the amyloid beta protein precursor (APP), superoxide dismutase 1 (SOD1), the ets-2 proto-oncogene (ETS2), the estrogen inducible breast cancer locus (BCEI), and the leukocyte antigen, CD18 (CD18). Segregation of RFLPs detected by these DNA markers was traced in the Venezuelan Reference Pedigree (VRP). A comprehensive genetic linkage map consisting of the 27 DNA markers spans 102 cM on the long arm of chromosome 21. We have confirmed our initial findings of a dramatically increased rate of recombination at the telomere in both females and males and of significantly higher recombination in females in the pericentromeric region. By comparing patterns of recombination in specific regions of chromosome 21 with regard to both parental sex and age, we have now identified a statistically significant downward trend in the frequency of crossovers in the most telomeric portion of chromosome 21 with increasing maternal age. A less significant decrease in recombination with increasing maternal age was observed in the pericentromeric region of the chromosome. These results may help in ultimately understanding the physical relationship between recombination and nondisjunction in the occurrence of trisomy 21.

Adolescent↗
PubMed1991

DNA sequences of chromosome 21-specific YAC detect the t(8;21) breakpoint of acute myelogenous leukemia.

The t(8;21)(q22;q22) is a nonrandom translocation specifically marking blasts of acute myelogenous leukemia (AML) with undifferentiated phenotype. The breakpoint on chromosome 21 involved by this rearrangement has been precisely localized relative to cloned DNA markers by physical and genetic linkage analysis enabling the use of positional cloning for its isolation. Yeast artificial chromosome (YAC) clones for loci proximal (D21S65) and distal (ERG) to the (21q22) breakpoint have been developed and their chromosome 21 origin and location relative to the breakpoint has been established. By using in situ hybridization analysis, a 240 kb YAC clone for the D21S65 locus clearly identified both derivative chromosomes of the (8;21) translocation in metaphase spreads of leukemia blasts with the rearrangement. The characterization of the DNA sequences contained in this 240 kb YAC can reveal the functional consequences of their derangement in leukemia with abnormalities of the (21q22) region.

Base Sequence↗
PubMed1991

Rapid and efficient cloning of Alu-PCR products using uracil DNA glycosylase.

By incorporating dUMP residues into the 5' end of PCR primers, one can generate products which, after treatment with uracil DNA glycosylase (UDG), contain 3' overhangs. These overhangs can be annealed to vector molecules with complementary overhangs generated in a similar fashion and transformed directly into Escherichia coli without the need for ligase. We have tested this method of ligation-independent cloning by using UDG to create complementary single-stranded sticky ends between vector and Alu-PCR products generated from cosmid clones containing DNA from human chromosome 21. Using a single primer, Alu-PCR amplifies the sequence between appropriately oriented, repetitive (Alu) sequences in human DNA that are no more than 2 to 3 kb apart. Nineteen Alu-PCR products were observed in four human chromosome 21 cosmids. Thirteen of these products were detected among 48 subclones picked at random after cloning of the Alu-PCR products using UDG. The size or abundance of an Alu-PCR product did not appear to affect significantly the efficiency of cloning. Eight of the subclones were tested and all hybridized to human chromosome 21 DNA. UDG cloning should prove to be a general PCR cloning method that allows one to rapidly subclone small fragments from human genomic DNA.

Base Sequence↗
PubMed1990

Hereditary spherocytosis associated with deletion of human erythrocyte ankyrin gene on chromosome 8.

Hereditary spherocytosis (HS) is one of the most common hereditary haemolytic anaemias. HS red cells from both autosound dominant and recessive variants are spectrin-deficient, which correlates with the severity of the disease. Some patients with recessive HS have a mutation in the spectrin alpha-2 domain (S.L.M. et al., unpublished observations), and a few dominant HS patients have an unstable beta-spectrin that is easily oxidized, which damages the protein 4.1 binding site and weakens spectrin-actin interactions. In most patients, however, the cause of spectrin deficiency is unknown. The alpha- and beta-spectrin loci are on chromosomes 1 and 14 respectively. The only other genetic locus for HS is SPH2, on the short arm of chromosome 8 (8p11). This does not correspond to any of the known loci of genes for red cell membrane proteins including protein 4.1 (1p36.2-p34), the anion exchange protein (AE1, band 3; 17q21-qter), glycophorin C (2q14-q21), and beta-actin (7pter-q22). Human erythrocyte ankyrin, which links beta-spectrin to the anion exchange protein, has recently been cloned. We now show that the ankyrin gene maps to chromosome 8p11.2, and that one copy is missing from DNA of two unrelated children with severe HS and heterozygous deletions of chromosome 8 (del(8)(p11-p21.1)). Affected red cells are also ankyrin-deficient. The data suggest that defects or deficiency or ankyrin are responsible for HS at the SPH2 locus.

Ankyrins↗
PubMed1990

Down syndrome critical region around D21S55 on proximal 21q22.3.

We have analysed the DNA of 2 patients with many manifestations of Down syndrome and partial duplication of distinct regions of chromosome 21, respectively, q11.205----q22.300 and q22.300----qter (Rahmani et al.: Proceedings of the National Academy of Sciences of the United States of America 86:5958-5962, 1989). Assessment of the copy number of five chromosome 21 sequences (SOD1, D21S17, D21S55, ETS2, and D21S15) has shown that D21S55 was duplicated in both cases. The size of the common duplicated region can be estimated between 400 and 3,000 Kb, after the results of pulsed-field gel analysis and from the knowledge of regional mapping of the probes D21S17, D21S55, and ETS2. This region, located on the proximal part of 21q22.3, is postulated to contain genes the overexpression of which plays a major role in the pathogenesis of Down syndrome.

Child↗
PubMed1990

Assignment of the gene for beta-spectrin (SPTB) to chromosome 14q23----q24.2 by in situ hybridization.

Type I hereditary spherocytosis results from a molecular defect in the beta-polypeptide of the erythrocyte cytoskeletal protein spectrin. Using a cDNA probe, we had previously assigned the gene for human erythrocyte beta-spectrin (SPTB) to chromosome 14 based upon analysis of its segregation in panels of human x rodent somatic cell hybrids (Winkelmann et al., 1988). Here we report the regional localization of this gene by in situ hybridization to 14q23----q24.2.

Chromosome Mapping↗
PubMed1990

Isolation and characterization of DNA probes for human chromosome 21.

A coordinated effort to map and sequence the human genome has recently become a national priority. Chromosome 21, the smallest human chromosome accounting for less than 2% of the human genome, is an attractive model system for developing and evaluating genome mapping technology. Several strategies are currently being explored including the development of chromosome 21 libraries from somatic cell hybrids as reported here, the cloning of chromosome 21 in yeast artificial chromosomes (McCormick et al., 1989b), and the construction of chromosome 21 libraries using chromosome flow-sorting techniques (Fuscoe et al., 1989). This report describes the approaches used to identify DNA probes that are useful for mapping chromosome 21. Probes were successfully isolated from both phage and cosmid libraries made from two somatic cell hybrids that contain human chromosome 21 as the only human chromosome. The 15 cosmid clones from the WA17 library, reduced to cloned DNA sequences of an average size of 3 kb, total 525 kb of DNA which is approximately 1% of chromosome 21. From these clones, a set of polymorphic DNA markers that span the length of the long arm of chromosome 21 has been generated. All of the probes thus far analyzed from the WA17 libraries have been mapped to chromosome 21 both by physical and genetic mapping methods. It is therefore likely that the WA17 hybrid cell line contains human chromosome 21 as the only human component, in agreement with cytogenetic observation. The 153E7b cosmid libraries will provide an alternative source of cloned chromosome 21 DNA. Library screening techniques can be employed to obtain cloned DNA sequences from the same genetic loci of the two different chromosome 21s. Comparative analysis will allow direct estimation of DNA sequence variation for different regions of chromosome 21. Mapped DNA probes make possible the molecular analysis of chromosome 21 at a level of resolution not achievable by classical cytogenetic techniques (Graw et al., 1988; Van Keuren et al., 1989). Methods based on using region-specific chromosome 21 DNA probes and fluorescence in situ hybridization show promise for the rapid diagnosis of trisomy 21 (Lichter et al., 1988). The continued development of chromosome 21 DNA probes and advances in the technology of molecular cytogenetics will facilitate the study of the genetic organization of chromosome 21 and its role in the pathogenesis of Down syndrome.

Chromosomes, Human, Pair 21↗