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Biomedical subjects

C G Palmer

Publications and source records attributed to C G Palmer.

At least 19 recordsLinked to original sources
PubMed1999

Cytogenetic analyses of 85 testicular germ cell tumors: comparison of postchemotherapy and untreated tumors.

Cytogenetic analyses of 85 testicular germ cell tumors, of which 54 were karyotypically abnormal, showed recurrent breakpoints at chromosome bands 1p36, 1p13-1qh, 11q23, 19q13, and the pericentromeric regions of the acrocentric chromosomes. Postchemotherapy tumors had significantly more rearrangements of bands 3p25-p26, 6q16-q21, 8p22-p23 when compared with untreated tumors, while untreated tumors had more rearrangements of 9p22-p24 when compared with postchemotherapy tumors. Frequent breakpoints also were identified at 15q15 and 9qh in untreated tumors. Tumors of different histopathology, clinical stage, and treatment status showed no significant differences in the frequencies of i(12p)-positive and i(12p)-negative tumors.

Adult↗
PubMed1999

Extensive analysis of mosaicism in a case of Turner syndrome: the experience of 287 cytogenetic laboratories. College of American Pathologists/American College of Medical Genetics Cytogenetics Resource Committee.

OBJECTIVE: To assemble and interpret karyotype data provided as part of the College of American Pathologists/American College of Medical Genetics Cytogenetics Proficiency Testing Program. DATA SOURCES, EXTRACTION, AND SYNTHESIS: The Cytogenetics Resource Committee requested data on all cells analyzed in a 1994 whole-blood specimen challenge. In that study, 287 participating laboratories analyzed a total of 14297 cells derived from a sample drawn from an adult donor with Turner syndrome. This individual had previously been found to have mosaicism, including cell lines with X structural anomalies along with monosomy X, making this an excellent challenge for a multicenter cytogenetic survey. RESULTS AND CONCLUSIONS: Analysis of the data from this extensive study revealed mosaicism of up to 10 different sex chromosome complements involving the X chromosome with and without a small ring X or a derivative X chromosome. In the routine cytogenetic analysis performed by the participating laboratories, cell lines observed, in decreasing order of prevalence, included 45,X (n = 8357 cells), 46,X,r(X) (n = 3597), 46,X,der(X)t(X;X) (n = 2237), 46,XX (n = 93), 47,X,r(X),r(X) (n = 5), 47,X,der (X)t(X;X),der(X)t(X;X) (n = 3), 47,XX,r(X) (n = 2), and one observation each of 47,XX,der(X)t(X;X), 47,X,der(X)t (X;X),r(X), and 47,XXX. Our molecular cytogenetic data, as well as detailed analysis of G-banded chromosomes, suggest the nomenclature for these 2 abnormal X chromosomes as r(X)(p11.3q21.3) and der(X)t(X;X)(p11.3;q21.3), and we discuss models for the concomitant formation of these 2 entities. Both the degree of analysis and the extensive mosaicism that was discovered in this study are exceptional, and similar reported cases as well as possible mechanisms for the observed X chromosome instability are reviewed.

Adult↗
PubMed1998

Molecular cytogenetic analysis of patients with holoprosencephaly and structural rearrangements of 7q.

The holoprosencephaly (HPE) sequence is a malformation complex with abnormal midline cleavage of the embryonic forebrain. HPE is genetically heterogeneous with at least 6 different chromosome regions containing genes involved in the expression of the phenotype. HPE3, recently identified as the human Sonic hedgehog gene, is localized to 7q36. We have used fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) amplification in 5 cell lines from patients with HPE (3 cases), HPE and sacral agenesis (1 case), and microcephaly (1 case) to further define the structural rearrangements of the long arm of chromosome 7 in each case. All cell lines demonstrated loss of material in the critical region of HPE3 at band 7q36, which includes the Sonic hedgehog gene. We report here the analysis of these patient cell lines.

Cell Line↗
PubMed1998

Evidence that the dopamine D4 receptor is a susceptibility gene in attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioral problem afflicting 5-10% of children and adolescents and persisting into adulthood in 30-50% or more of cases. Family, twin, and adoption studies suggest genetic factors contribute to ADHD and symptoms of inattention, impulsivity, and hyperactivity. Because stimulant intervention is effective in reducing ADHD symptoms in about 70-80% of cases, molecular genetic investigations of genes involved in dopamine regulation are currently underway by many groups. In a case control study of the dopamine D4 receptor gene (DRD4) and ADHD, La Hoste and colleagues found an increase of a 7-repeat variant of a 48-bp VNTR in exon 3 among ADHD subjects compared to controls. Swanson and colleagues replicated this finding in a sample of 52 ADHD probands and their biological parents using a haplotype relative risk analysis. Here, we describe linkage investigations of the VNTR and ADHD in affected sibling pair (ASP) families and singleton families using both the transmission disequilibrium test (TDT) and a mean test of identity-by-descent (IBD) sharing. Using the TDT in the total sample, the 7 allele is differentially transmitted to ADHD children (P = 0.03) while the mean test revealed no evidence of increased IBD sharing among ASPs. In the current sample, the 7 allele attributes a 1.5-fold risk for developing ADHD over non-carriers of the allele estimated under a model described by Risch and Merikangas.

Adult↗
PubMed1997

An apparently acentric marker chromosome originating from 9p with a functional centromere without detectable alpha and beta satellite sequences.

Recently, we studied a patient with minor abnormalities and an apparently acentric marker chromosome who carried a deleted chromosome 9 and a marker chromosome in addition to a normal chromosome 9. The marker was stable in mitosis but lacked a primary constriction. The origin of the marker was established by fluorescent in situ hybridization (FISH) using a chromosome 9 painting probe. Hybridization of unique sequence 9p probes localized the breakpoint proximal to 9p13. Additional FISH studies with all-human centromere alpha satellite, chromosome 9 classical satellite, and beta satellite probes showed no visible evidence of these sequences on the marker [Curtis et al.: Am J Hum Genet 57:A111, 1995]. Studies using centromere proteins (CENP-B, CENP-C, and CENP-E) were performed and demonstrated the presence of centromere proteins. These studies and the patient's clinical findings are reported here.

Abnormalities, Multiple↗
PubMed1997

PCR and FISH analysis of a ring Y chromosome.

A newborn male infant presented with midshaft hypospadias, chordee, and undescended left testis. Both gonads lacked the tunica albuginea and appeared to be adjacent to structures resembling fallopian tubes. On biopsy, there was marked dysgenesis of both gonads, with a paucity of testicular tubules and foci of ovarian-like stroma. Peripheral blood karyotype was 46,X,mar(Y) [39]/45,X [5]. Right gonadal biopsy material showed the same mosaicism but with a higher proportion of 45,X cells (46%). PCR and FISH analyses with primers/probes from different Yp, Yq, and Ycen loci defined the structure of the marker Y as a probable complex ring with breakpoints in Yq11.21 (very close to the centromere) and in Yp11.32 (the pseudoautosomal region). Based on the phenotype and the laboratory findings, the prognosis given to the patient was for short stature and azoospermia without an increased risk for gonadoblastomas.

Abnormalities, Multiple↗
PubMed1997

Molecular cytogenetic identification of four X chromosome duplications.

Four cases with previously unidentified X-chromosome abnormalities were studied by standard cytogenetic techniques and FISH in order to demonstrate the origin of the extra segment on the abnormal X chromosomes. All cases were identified as X-chromosome duplications by using a chromosome-specific painting probe. Application of appropriate locus-specific DNA probes as an adjunct to GTG- and RBG-banding proved useful in defining the breakpoints and the extent of the duplications. Although the duplicated X chromosome in female cases was selectively inactivated, as demonstrated by its late-replicating pattern, abnormal clinical findings were manifested in 3 female patients.

Adult↗
PubMed1997

A multivariate approach to affected-sib-pair analysis using highly dense molecular maps.

A multivariate approach to affected-sib-pair analyses was performed to localize disease-susceptibility genes with a minimum number of type I errors (false positives). Using 1,155 independent affected sib pairs extracted from Problem 2A of the GAW10 data set, we were able to localize major genes (MG) 1 and 2. Using 30% of the affected-sib-pair sample (N = 337) we were able to localize MG1. False positives were not detected in either of these samples.

Computer Simulation↗
PubMed1997

The calibration of an artificial stream system used to investigate the tolerances of South African riverine invertebrates to selected water quality variables.

Water quality management in South Africa aims at the maintenance of water in a state that is "fit for use." This includes use for agriculture, industry, domestic supply, and recreation,together with the maintenance of the natural, functioning resource base:aquatic ecosystems. The water quality requirements of riverine ecosystems need to be established to fulfil this last aim. A first step is the investigation of the tolerances of a range of riverine organisms to key water quality variables or pollutants. However, riverine organisms require flowing water, and in order to provide a flowing water experimental facility, an artificial stream laboratory has been developed. The objective of calibrating this system was to establish the physical and chemical conditions in the streams before test organisms were introduced; then to monitor behavior of organisms in the streams before water quality conditions were experimentally altered. This paper introduces the concept of system calibration and reports on hydraulic and water quality calibration, and the effects of handling on test organisms.

Analysis of Variance↗
PubMed1997

Salinity tolerances of selected macroinvertebrates of the Sabie River, Kruger National Park, South Africa.

Salinization has been identified as the most important problem facing the managers of South African freshwaters. Laboratory-based toxicity tests were conducted to assess the tolerance of selected macroinvertebrates to elevated salt concentrations. Since the Kruger National Park is the focus of river research in South Africa, and the Sabie River is the least mineralized river in the park, 96-h acute toxicity tests were conducted using Sabie River water and an ephemeropteran mayfly Tricorythus sp. found in the river. Experiments were conducted inflowing water systems known as raceways. The tolerance of the mayfly to two sodium salts, sodium chloride and sodium sulphate, was assessed at a range of selected conductivity levels/concentrations. The results indicated that mortality cannot be linked only to conductivity or total dissolved solid(TDS) concentrations, but also to the nature of the salt. Sodium sulphate was considerably more toxic to Tricorythus sp. than sodium chloride. Causes of mortality and implications for the development of water quality guidelines for the natural aquatic environment are discussed.

Animals↗
PubMed1996

Breakage in the SNRPN locus in a balanced 46,XY,t(15;19) Prader-Willi syndrome patient.

A patient with Prader-Willi syndrome (PWS) was found to carry a de novo balanced reciprocal translocation, t(15;19)(q12;q13.41), which disrupted the small nuclear ribonucleoprotein N (SNRPN) locus. The translocation chromosome 15 was found to be paternal in origin. Uniparental disomy and abnormal DNA methylation were ruled out. The translocation breakpoint was found to have occurred between exon 0 (second exon) and 1 (third exon) of the SNRPN locus outside of the SmN open reading frame (ORF), which is intact. The transcriptional activities of ZNF127, IPW, PAR-1, and PAR-5 were detected with RT-PCR from fibroblasts of the patient, suggesting that these genes may not play a significant role in the PWS phenotype in this patient. Transcription from the first two exons and last seven exons of the SNRPN gene was also detected with RT-PCR; however, the complete mRNA (10 exons) was not detected. Thus, the PWS phenotype in the patient is likely to be the result of disruption of the SNRPN locus.

Autoantigens↗
PubMed1996

Risk perception: an empirical study of the relationship between worldview and the risk construct.

This study empirically assesses the performance of Holtgrave and Weber's Simplified Conjoint Expected Risk (SCER) model for financial and health stimuli in 3 groups of "worldview holders"-12 hierarchists, 10 individualists, and 16 egalitarians-as described by cultural theory. The SCER model performed well, however, distinctive patterns of model variable selection appeared within each group. Interestingly, the pattern of variable selection paralleled cultural theory's descriptions of each worldview. Differences in the mean perceived risk of activities also tended to correspond to predictions made by cultural theory. Results suggest two mechanisms to explain differences in perceived risk among worldviews: (i) same model variables are evaluated, but given different weight; (ii) different variables are evaluated. Identifying the relevant mechanism for a given situation may enhance the effectiveness of risk communication.

Adult↗
PubMed1996

A general statistical model for detecting complex-trait loci by using affected relative pairs in a genome search.

Scanning of the human genome by use of affected relative pairs and dense sets of highly polymorphic markers or by emerging techniques such as genomic mismatch scanning. (GMS) is making it possible to identify the genetic etiology of a disease through detection of susceptibility loci. We present a general statistical model and test to detect disease genes, using affected relative pairs and either markers or GMS technologies in a genome search. There are an exact test and large-sample normal approximation that control for the elevated probability of false detection of linkage in a genome search. The approach can be used to determine the sample size needed to obtain a prespecified power to detect a disease gene in the presence of etiologic heterogeneity for a single class or mixture of relative classes, with any number of markers, or clones, markers PIC values, or mapping function. The approach is used to examine differences in performance of markers and GMS technologies in a common statistical framework and to provide practical information for designing studies of complex traits.

Alleles↗
PubMed1995

Cytogenetic and molecular analysis of a ring (21) in a patient with partial trisomy 21 and megakaryocytic leukemia.

We describe a patient with an asymmetric double ring 21 in mosaic form, 45,XX, -21/46, XX, -21, +r(21), who has limited manifestations of Down syndrome and who developed acute myelofibrosis and megakaryocytic leukemia (AMKL), FAB M7, a hematologic disorder particularly common in Down syndrome patients. In situ hybridization studies, gene dosage, and DNA polymorphism analysis showed that the ring chromosome carries a duplicated region which extends from D21S406 on the centromeric side and includes marker D21S3 on the telomeric side. FISH studies indicate two sizes of ring 21 in the patient. The origin of the supernumerary chromosome 21 in the proband was paternal; furthermore, the r(21) probably was formed postzygotically. Included in the duplicated segment are the candidate genes for leukemia AML-1, ETS, and ERG. The potential significance of disomic homozygosity of loci on 21q in M7 megakaryocytic leukemia is discussed.

Chromosome Mapping↗
PubMed1995

Marker chromosome 21 identified by microdissection and FISH.

A child without Down syndrome but with developmental delay, short stature, and autistic behavior was found to be mosaic 46,XX/47,XX,+mar(21) de novo. The marker was a small ring or dot-like chromosome. Microdissection of the marker was performed. The dissected fragments were biotinylated with sequence-independent PCR as a probe pool for fluorescence in situ hybridization (FISH). FISH results suggested an acrocentric origin of the marker. Subsequent FISH with alpha-satellite DNA probes for acrocentric chromosomes, and chromosome-specific 21 and 22 painting probes confirmed its origin from chromosome 21.

Child, Preschool↗
PubMed1995

Familial translocation resulting in Wolf-Hirschhorn syndrome in two related unbalanced individuals: clinical evaluation of a 39-year-old man with Wolf-Hirschhorn syndrome.

A chromosomal translocation between chromosomes 4 and 8 resulting in Wolf-Hirschhorn syndrome in 2 individuals has been traced through 4 generations of a family. Ascertainment of the family was through a newborn infant with evident Wolf-Hirschhorn syndrome who had an unbalanced chromosomal translocation [46,XY,-4,+der(4),t(4;8) (p15.32;p22)]. Discussion with the family documented a paternal great-uncle who also had a similar phenotype and profound mental retardation. Subsequently this individual was found to have the same unbalanced chromosome constitution as the propositus. The 39-year-old great-uncle is the oldest reported individual with the Wolf-Hirschhorn syndrome. The importance of chromosome evaluation of older individuals with mental retardation syndromes is emphasized.

Abnormalities, Multiple↗