Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “phenotypes”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30Linked to original sources
PubMed1994

Separation of phenotypically distinct subpopulations of cultured human retinal pigment epithelial cells.

Like most epithelial cells that are isolated from tissues and placed in culture, the phenotype of human retinal pigment epithelial cells (RPE) in vitro is more variable than for the same cells in situ. The phenotypic heterogeneity of the cultures has been attributed to varying stages of differentiation of the cells induced by the culture environment. In this study we show that within the same cultures RPE cells exist as phenotypic variants which are distinct and stable. Two phenotypically distinct subpopulations were identified, one epithelioid and one fusiform, that were present from the first spreading event in primary culture through multiple serial passages and when maintained for extended periods at confluency. Cell aggregation studies indicated differences in cellular adhesions, known determinants of cell shape, between the subpopulations. Methods to separate the subpopulations were developed which are based on the differential trypsin sensitivity of adhesions. The separated subpopulations had the same RPE cytokeratins by immunoblotting, but cytokeratin filaments (and actin filaments) had different organizations. The study indicates that RPE cell cultures contain at least two subpopulations of phenotypically distinct cells under identical culture conditions that can be separated and propagated independently. The phenotypic variants offer a model system for investigating determinants of epithelial cell shape in RPE. Further, the separation methods might be applied to test for phenotypic variants in other types of cultured epithelia.

Actins↗
PubMed2000

The basis for the super-repressor phenotypes of the AV77 and EK18 mutants of trp repressor.

The DNA-binding properties of two super-repressor mutants of the Escherichia coli trp repressor, EK18 and AV77, have been investigated using steady-state fluorescence anisotropy measurements, in order to further elucidate the basis for their super-repressor phenotypes. Several suggestions have been previously proposed as the basis for the super-repressor phenotype of EK18 and AV77. For the negative to positive charge change EK18 mutant, increased electrostatic interactions between the EK18 mutant and the operator and increased protein-protein interactions between EK18 dimers have been suggested as contributing to the super-repressor phenotype of this mutant. We show that EK18 dimers actually bind to wild-type and variant operator sequences with a decrease in apparent cooperativity and an increase in affinity, compared to WTTR dimers. Thus, the EK18 super-repressor phenotype is not due to increased cooperative binding between EK18 dimers. These results support the hypothesis that the super-repressor phenotype of EK18 arises from increased electrostatic interactions between the mutant and DNA. In the case of the AV77 mutant, weaker binding affinity of apo-AV77 to non-specific DNA, increased selectivity of binding of AV77 for the operator, and a higher population of folded functional AV77 dimers available to bind the operator under limiting L-Trp conditions in vivo, have been proposed for the super-repressor phenotype of this mutant. We show that like the EK18 mutant, apoAV77 binds with higher affinity to non-specific DNA compared to apo-WTTR and that the holo-AV77 mutant does not bind with higher selectivity to the operator, has had been previously proposed. We therefore conclude that the super-repressor phenotype of the AV77 mutant is due to an increase in the population of folded, functional AV77 dimers, under limiting L-Trp conditions in vivo.

Apoproteins↗
PubMed2002

Mistranslation induced by streptomycin provokes a RecABC/RuvABC-dependent mutator phenotype in Escherichia coli cells.

Translational stress-induced mutagenesis (TSM) refers to the mutator phenotype observed in Escherichia coli cells expressing a mutant allele (mutA or mutC) of the glycine tRNA gene glyV (or glyW). Because of an anticodon mutation, expression of the mutA allele results in low levels of Asp-->Gly mistranslation. The mutA phenotype does not require lexA-regulated SOS mutagenesis functions, and appears to be suppressed in cells defective for RecABC-dependent homologous recombination functions. To test the hypothesis that the TSM response is mediated by non-specific mistranslation rather than specific Asp-->Gly misreading, we asked if streptomycin (Str), an aminoglycoside antibiotic known to promote mistranslation, can provoke a mutator phenotype. We report that Str induces a strong mutator phenotype in cells bearing certain alleles of rpsL, the gene encoding S12, an essential component of the ribosomal 30 S subunit. The phenotype is strikingly similar to that observed in mutA cells in its mutational specificity, as well as in its requirement for RecABC-mediated homologous recombination functions. Expression of Str-inducible mutator phenotype correlates with mistranslation efficiency in response to Str. Thus, mistranslation in general is able to induce the TSM response. The Str-inducible mutator phenotype described here defines a new functional class of rpsL alleles, and raises interesting questions on the mechanism of action of Str, and on bacterial response to antibiotic stress.

Anti-Bacterial Agents↗
PubMed1993

Alteration of cardiac collagen phenotypes in hypertensive hypertrophy: role of blood pressure.

The myocardium contains a fibrillar collagen matrix that consists primarily of type I and type III collagens. There is a marked alteration in the ratio and amount of collagen phenotypes in myocardial hypertrophy due to pressure overload. The purpose of the present study is (1) to study the effect of antihypertensive therapy on collagen phenotypes, if instituted before development of hypertension in spontaneously hypertensive rat (SHR), and continued into adult life and (2) to study the effects of dissociation of hypertension from hypertrophy, on collagen phenotypes in SHRs. The present study shows the effect of two antihypertensive drugs, hydralazine and captopril, on collagen phenotypes in SHRs. Both hydralazine and captopril effectively controlled blood pressure in SHRs, but only captopril regressed hypertrophy and corrected the altered distribution of myocardial collagen phenotypes I and III. Untreated SHRs had a collagen type I:III ratio of 10.19 +/- 0.27, compared with that of 6.41 +/- 0.30 in normotensive WKY (P < 0.001). Captopril-treated SHRs had a collagen type I:III ratio of 6.75 +/- 0.37, which did not differ significantly from that in normotensive WKY. Hydralazine-treated SHRs had a collagen I:III ratio of 10.07 +/- 0.39, which is similar to the ratio in untreated SHRs. In normotensive rats, neither captopril nor hydralazine significantly altered collagen content or the ratio of type I:III collagen. Thus captopril, an angiotensin converting enzyme inhibitor, not only regressed hypertrophy but also reversed the altered distribution of type I and type III collagen whereas hydralazine which effectively controlled blood pressure, did not regress hypertrophy and did not correct the altered distribution in collagen phenotypes. These studies suggest that alteration of collagen phenotypes during hypertensive hypertrophy is independent of blood pressure control and myocardial mass.

Animals↗
PubMed1994

Complex interactions among several nucleotide positions determine phenotypes defective for long-distance transport in the satellite RNA of cucumber mosaic virus.

Ix-satRNA is a CMV-satRNA necrogenic on tomato that is defective for long-distance systemic movement when coinoculated in tobacco with V-TAV. To analyze the determinants for this defective phenotype, full-length cDNA clones of Ix-satRNA and of the closely related, nondefective I17N-satRNA were obtained. Infectious transcripts from these clones (Ix5-satRNA and I17N1-satRNA) had the same phenotypes as the original satRNAs and differed only in four positions: positions 20 (Ix5, C; I17N1, U), 102 (Ix5, C; I17N1, U), 224 (Ix5, deleted; I17N1, A), 327 (Ix5, G; I17N1, A). By site-directed mutagenesis at positions 224 and 327 and by recombination using two common restriction sites, satRNAs in which the bases at these four positions were changed from the composition at Ix5-satRNA to the composition at I17N1-satRNA were obtained. A comparison of the phenotypes of the 13 single, double, and triple mutants (respective to Ix5-satRNA) showed that the defective phenotype of Ix5-satRNA is determined by the nature of the four positions analyzed; mutants at any of the positions 102, 224, and 327 accumulated as efficiently as I17N1-satRNA in systemically infected tobacco leaves when coinoculated with V-TAV. The change C20-->U also restored systemic movement, albeit imperfectly, giving rise to a phenotype that moved systemically less efficiently than I17N1-satRNA. This phenotype determined by U20 is expressed irrespective of the base at position 102, indicating an epistatic interaction between determinants 20 and 102; this interaction does not occur with position 224 or 327. That differences in the analyzed satRNAs are due to their being able, or not, to move systemically is shown by the fact that all of them (including Ix5-satRNA) accumulated to the same high level in directly inoculated leaves. The similarity in the sequences of the analyzed satRNAs and the complexity of the interactions among the effects of base changes at four positions scattered over the satRNA molecule suggest that the observed movement phenotypes may depend on conformational changes in the satRNAs.

Base Sequence↗
PubMedDate not supplied

Multiple phenotypic divergence of mammary adenocarcinoma cell clones. I. In vitro and in vivo properties.

The properties of cell clones derived from locally growing and spontaneous metastases of 13762NF mammary adenocarcinoma change during in vitro growth. This has been termed phenotypic drift and is reproducible in independent experiments using different cryoprotected cell stocks. To determine whether phenotypic drift in 13762NF cell clones is the result of an en bloc shift in the properties of all tumor cells, or independent phenotypic divergence of tumor cells to produce a mixed cell population, local tumor-derived clone MTF7 was subcloned at low and high culture passage numbers in vitro. Each subclone was analyzed in vitro for cell morphology, growth rate, saturation density, karyotype and ploidy, and in vivo for experimental metastatic behavior. Subclones derived from low passage clone MTF7 (T11; tissue culture passage number 11) were relatively homogeneous in their growth rates (doubling times of 16.8-17.4 h) and saturation densities (approximately 2 X 10(5) cells/cm2); yet, these same subclones were heterogeneous in their in vitro cell morphologies, experimental metastatic potentials (means range from 0 to greater than 100 tumor nodules per lung), size distributions of lung tumor nodules, marker chromosomes and modal chromosome numbers. High passage MTF7 (T35; tissue culture passage number 35) subclones had similar growth rates and saturation densities, except for subclone 2, which had a doubling time of approximately 26 h. Cell morphologies, experimental metastatic potentials (means range from 3 to greater than 600 tumor nodules per lung), size distribution of lung tumor nodules, marker chromosomes and modal chromosome numbers varied between MTF7 (T35) subclones. The results suggest that simultaneous, independent divergence of several phenotypes from a single cloned cell occurred to form a mixed cell population containing cells with independently segregated, unrelated phenotypes. Thus, the reproducibility of phenotypic drift in clonal cell populations was probably the result of tumor cell divergence and was not an en bloc shift in phenotypic properties of all cells.

Adenocarcinoma↗
PubMed1995

The genetic contribution to the phenotype.

The phenotype is the result of ontogenetic development. This holds true also at the molecular level, because molecular biological processes take place within the organism. In ontogenesis, genetic and nongenetic factors interact in producing successive states, each of which is the prerequisite, and determines the conditions, for the next one to follow. In this interplay, genes are a necessary, but not sufficient, component. The structures already present, gradients, threshold values, positional relationships, and conditions of the internal milieu, are equally essential. Thus, even monofactorial traits can be considered to be of multifactorial causation, and the varying borderline conditions that arise during development add to the complexity. From this standpoint, it is not to be expected that a mutation has a consistent phenotypic outcome, and the genotype-phenotype relationship may be irregular. In the present review, genotypic heterogeneity versus phenotypic heterogeneity is discussed with the help of some selected examples of hereditary diseases. Conditions and mechanisms contributing to this heterogeneity are addressed. It is concluded that the genotype-phenotype relationship is neither unidimensional, programmatical nor hierarchical in a strict sense. Nevertheless, in particular cases, ontogenetic modification appears to be of minor significance, so that the phenotype of a mutation can be predicted with considerable accuracy. This is no surprise if, depending on the nature of the mutation and the physiological function of the gene affected, the genotype-phenotype relationship is direct. However, this relationship may also be consistent in more complex conditions. It is assumed that the total of the non-genetic influences (epigenetic, environmental) are usually so similar or are compensated by the organism to such an extent that the respective mutation acts as the major variable during ontogenetic development.

Genotype↗
PubMed1982

Analysis of the phenotypes exhibited by rudimentary-like mutants of Drosophila melanogaster.

Flies mutant for one or both of the last two enzymes of de novo pyrimidine biosynthesis express a number of phenotypes that are also expressed by mutants of the first four pathway enzymes (r and Dhod-null mutants). However, r-1 flies also express two phenotypes, mottled eyes and poor viability, that are not usually expressed by r and Dhod-null flies. Chemical determinations show that orotic acid, a substrate for the fifth pathway enzyme, accumulates in r-1 individuals but not in r and wild-type individuals. Moreover, flies simultaneously mutant for r and r-1 do not express the mottled-eye phenotype, showing that r is epistatic to r-1 for this r-1-specific phenotype. When genotypically wild-type flies are cultured on a medium containing 6-azauracil, the base of a potent inhibitor of the last enzyme of de novo pyrimidine biosynthesis, phenocopies are obtained that include the mottled-eye as well as the wing phenotypes of r-1 flies. These results support hypotheses that the phenotypes common to r, Dhod-null, and r-1 flies are consequences of uridylic acid deficiency, whereas the r-1-specific phenotypes result from orotic acid accumulation in flies lacking either or both of the last two enzymes of de novo pyrimidine biosynthesis.

Animals↗
PubMed2003

Phenotype score to grade the severity of thalassemia intermedia.

OBJECTIVE: Thalassemia intermedia is an ill-defined group of thalassemia patients with severity in between thalassemia major and asymptomatic carriers. The severity of cases varies greatly. With availability of information about genetic modifiers of beta-thalassemia phenotype, attempts are being made to study genotype phenotype correlation in thalassemia intermedia. METHODS: The first important step in genotype, phenotype correlation is well-defined phenotypes. Severity of thalassemia intermedia can not be graded only on haemoglobin level and age of presentation. The authors have developed a phenotype scoring system to subclassify thalassemia intermedia patients into 3 groups, viz, mild, moderate and severe. RESULT: This phenotype scoring system appears to grade the severity correctly depending on various clinical features like age of presentation, severity of anaemia, growth retardation, bone marrow hyperplasia, need of blood transfusions and splenectomy. CONCLUSION: The classification of thalassemia intermedia will be useful for genotype phenotype correlation, to develop management guidelines for the subgroups and to try new treatment modalities like hydroxyurea, erythropoetin etc.

Adolescent↗
PubMed2003

Frequencies of the hereditary hemochromatosis allele in different populations. Comparison of previous phenotypic methods and novel genotypic methods.

AIM: The frequencies of the hereditary hemochromatosis allele were compared for different populations assessed by previous phenotypic methods and the present genotypic methods. METHODS: From a literature survey, the calculated hemochromatosis allele frequencies from 16 studies using phenotypic biochemical markers (threshold levels for transferrin saturation [range, 46%-70%] and serum ferritin [range, 164-700 microg/L]) were compared with allele frequencies of the Cys282Tyr mutation of the hemochromatosis gene reported in 19 genotypic studies. RESULTS: Calculated phenotypic allele frequencies are high in Scandinavia: Iceland, 6.1% to 7.4%; Norway, 5.8%; central Sweden, 6.3% to 6.9%; Denmark, 6.1%. Frequencies are similarly high in Wales, Canada, Utah, South Africa, and Australia (range, 5.2%-9.8%). Frequencies are low in Finland (1.9%) and northern Italy (4.5%). Genotypic allele frequencies of the Cys282Tyr mutation are likewise high in Scandinavia. Frequencies are high in the United Kingdom and northern France and low in Finland, central Germany, northern Italy, and Greece. The phenotypic-genotypic ratios of the hemochromatosis homozygosity frequencies for the same geographic area were calculated. A ratio of 1.0 indicates that the 2 methods give similar results. In 3 studies, the ratio was above 1.0, the highest ratio of 1.67 being reported from Italy. In most studies the ratio was slightly below 1.0 (0.71-0.97). The lowest ratio was found in Finland (0.33). CONCLUSION: In most studies there was good agreement between the hemochromatosis allele frequencies determined by phenotypic and genotypic methods. A high ratio (northern Italy) may indicate that phenotypic selection criteria were too loose and/or that causes of iron overload other than the Cys282Tyr mutation are frequent in the region. A low ratio (in Finland) may indicate phenotypic selection criteria that were too stringent and/or a low penetration rate of the mutation.

Biomarkers↗
PubMed2004

Re-investigation of the concordance of human NAT2 phenotypes and genotypes.

A comparative study of N-acetyltransferase 2 (NAT2) genotyping and phenotyping (caffeine test method) was performed on 211 persons to elucidate apparent discrepancies in the assignment of NAT2*12 and NAT2*13 alleles which occur in the literature. The study used the standard procedures of genotyping (two PCR runs and application of seven restriction enzymes) and phenotyping (determination of the two caffeine metabolites 5-acetylamino-6-formylamino-3-methyluracil (AFMU) and 1-methylxanthine (1X)), as documented in detail and validated by the Deutsche Forschungsgemeinschaft. The data were consistent with an AFMU/1X molar ratio of 0.85 as cut-off point (antimode) between phenotypically slow and rapid acetylators. Under this provision, several R/S allele combinations did not comply, either fully or partly, with their associated phenotypes. In particular, there was a wide phenotypic overlap of the alleged rapid allele combination groups (i) NAT2*12A/*5A; NAT2*12C/*5D; NAT2*4/*5B, (ii) NAT2*13/*6B; NAT2*4/*6A, and (iii) NAT2*13/*7A; NAT2*4/*7B. These groups obviously contained both phenotypically rapid and slow acetylators. If one assumes that the presence of one "wild type" allele NAT2*4 defines a rapid acetylator the assignment of the alleles NAT2*12A, NAT2*12C, and NAT*13 as determinants of a rapid acetylator phenotype must be questioned. This refers in particular to the nucleotide changes A803G (NAT2*12A, NAT2*12C) and C282T (NAT2*13). Based on discussions in the literature and the data presented here, there is accumulating evidence that current assignments of the NAT2*12 and NAT2*13 alleles as determinants of a rapid acetylator state should be reconsidered.

Acetylation↗
PubMed2000

Genotype and phenotype of cytochrome P450 2D6 in human immunodeficiency virus-positive patients and patients with acquired immunodeficiency syndrome.

OBJECTIVE: To examine the distribution of the cytochrome P450 (CYP) CYP2D6 phenotype and its relation to genotype, concomitant medication, and disease state in human immunodeficiency virus (HIV)-positive patients. DESIGN: A cross sectional study with a longitudinal component compared individual genotypes for CYP2D6 to the CYP2D6 phenotype. METHODS: Sixty-one predominately male Caucasian, HIV-positive patients were recruited and CYP2D6 genotypes [extensive metabolizer (EM) or poor metabolizer (PM)] determined by polymerase chain reaction (PCR)-based amplification, followed by restriction fragment-length analysis. The patients were also phenotyped using dextromethorphan (DM) to determine their respective enzyme activity and assigned either a CYP2D6 EM or PM phenotype. Complete medical and treatment histories were compiled. A total of 44 patients were tested longitudinally. RESULTS: Fifty-nine patients (97%) possessed an EM genotype, consistent with previously observed distributions in demographically similar populations. In healthy seronegative populations, genotype and phenotype have been shown to be essentially interchangeable measures of CYP2D6 activity. In this cohort, 2 of the 59 patients with an EM genotype expressed a PM phenotype. In addition, 4 EM patients were less extensive DM metabolizers than any of the patients receiving medication known to inhibit CYP2D6. This apparent shift toward the PM phenotype from the EM genotype was associated with the presence of active illness. CONCLUSION: Changes may occur in HIV-positive patients such that their CYP2D6 activity approaches that of PMs, despite having an EM genotype. Neither active disease nor drug interactions alone explain the shift.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Combining gene expression QTL mapping and phenotypic spectrum analysis to uncover gene regulatory relationships.

Gene expression QTL (eQTL) mapping can suggest candidate regulatory relationships between genes. Recent advances in mammalian phenotype annotation such as mammalian phenotype ontology (MPO) enable systematic analysis of the phenotypic spectrum subserved by many genes. In this study we combined eQTL mapping and phenotypic spectrum analysis to predict gene regulatory relationships. Five pairs of genes with similar phenotypic effects and potential regulatory relationships suggested by eQTL mapping were identified. Lines of evidence supporting some of the predicted regulatory relationships were obtained from biological literature. A particularly notable example is that promoter sequence analysis and real-time PCR assays support the predicted regulation of protein kinase C epsilon (Prkce) by cAMP responsive element binding protein 1 (Creb1). Our results show that the combination of gene eQTL mapping and phenotypic spectrum analysis may provide a valuable approach to uncovering gene regulatory relations underlying mammalian phenotypes.

Animals↗
PubMed2001

Stickler syndrome and vitreoretinal degeneration: correlation between locus mutation and vitreous phenotype. Apropos of a case.

BACKGROUND: Autosomal dominant vitreoretinopathies are characterized by genetic heterogeneity. Structural mutations in COL2A1 are the most frequent cause of Stickler syndrome with ocular involvement. The affected patients have a characteristic vitreous alteration, so-called membranous vitreous, or type 1 vitreous phenotype. Recently a novel mutation in the gene encoding the alpha 1 chain of type XI collagen (COL11A1) was reported in rare Stickler pedigrees, with a different, so-called beaded or type 2 vitreous phenotype. METHODS: Five patients of an Italian family affected by high myopia, high frequency of retinal detachment, and other systemic stigmata evocative of Stickler syndrome (flat midface, depressed nasal bridge, short nose, spondyloepiphyseal dysplasia and osteoarthritis) were studied. Genetic investigations were also performed, considering three candidate loci for Stickler syndrome and Wagner syndrome (COL2A1, COL11A1, WGN1). RESULTS: Segregation analysis was performed utilizing polymorphic markers. COL2A1 and WGN1 segregations were excluded; COL11A1 showed concordance with the disease. The vitreous phenotype of the family was a typical type 1 or "membranous" vitreous, although all the previously reported COL11A1-related Stickler syndromes had always shown the type 2 or "beaded" vitreous phenotype. CONCLUSIONS: The clear presence of the type 1 or "membranous" vitreous phenotype in our family, despite the probable mutation in the COL11A1 gene, suggests greater phenotypical heterogeneity and a more extensive mutation spectrum, even of the COL11A1 gene, than previously thought, explaining the basis for the different vitreous phenotypes seen in Stickler syndrome.

Child↗
PubMed2001

Time-dependent expression of intestinal phenotype in signet ring cell carcinomas of the human stomach.

Signet ring cell carcinomas of the stomach are thought to arise from the proper gastric mucosa without intestinal metaplasia. It was recently reported that intestinal phenotypes appear along with tumor progression. In this study, we performed several experiments to reconsider the significance of this intestinalization in the growth of signet ring cell carcinoma. We applied mucin histochemistry with monoclonal antibodies MUC2 (Ccp58) and M1 (45M1), and paradoxical concanavalin A staining for class III mucin [PCS(III)] reaction to 29 intramucosal and 25 deeply invasive carcinomas of this type and correlated the phenotypic expression with the size of the mucosal spread and the depth of tumor invasion. It was found that the larger the size of the mucosal lesion, the more frequently the intestinal phenotypes were demonstrated. There was no significant increase in the expression of the intestinal phenotype as the tumor invaded the deeper part of the mucosa or as the intestinal metaplasia increased in the background mucosa. The intestinal expression appeared to be suppressed in the earlier phase of deep invasion. In the mucosal part of the tumor, the intestinal phenotype was often expressed regionally and incompletely, coexisting with gastric phenotypes at the cellular and the tissue levels. These findings indicate that the expression of the intestinal phenotype is a time-dependent and unstable phenomenon probably based on the accumulation of genetic changes and plays a neutral role in progression of signet ring cell carcinomas.

Adult↗
PubMed1997

Phenotype of cultured fetal perivascular cells from human placenta studied by scanning electron microscopy.

The phenotype of perivascular placental cells has previously been studied using tissue sections from the fetal villi. The examination of these cells in culture by scanning electron microscopy gives us the opportunity to observe their three-dimensional phenotypes and associations outside their normal constraints. Human umbilical endothelial cells, which have a phenotype comparable to that observed in other studies, seem more flattened in culture than in their usual environment. Microvascular endothelial cells did not attain an epithelioid phenotype with close contacts between cells but formed a network of branched, elongated cells with phagocytotic activity. Some circular associations were observed when using a gelatinized matrix. Microvascular pericytes were large, flattened cells with an irregular border that pushed up nodular associations on a gelatin matrix. Chorioplacental myocytes adopted a network template comparable to that developed by microvascular endothelial cells. However, these elongated cells were thicker, without microvilli, and superficial filaments could be observed. In culture, confluent endothelial cells from the umbilical cord or microvascular pericytes associated as nodules reached a cell phenotype close to their in vivo counter-parts. This attainment of an in vivo phenotype remains questionable for chorioplacental myocytes. Microvascular endothelial cells, however, though there was sparse formation of circular associations, remained far from their in vivo phenotype.

Cell Differentiation↗
PubMed1998

Unusual features in children with inv dup(15) supernumerary marker: a study of genotype-phenotype correlation in Taiwan.

UNLABELLED: Recent molecular cytogenetic studies have elucidated the origin and nature of extra structurally abnormal chromosomes (ESACs) or small supernumerary chromosomes, which are often associated with developmental delay and malformations. We studied the prevalence of inv dup(15) in a nationwide screening programme for mentally retarded children in Taiwan and tried to correlate the genotype and phenotype in those patients. Fluorescence in situ hybridization (FISH) analysis using D15Z, D15Z1, and the cosmids from the Prader-Willi/Angelman syndrome chromosome region (PW/ASCR) was performed on 54 patients (0.45%) with ESACs from 11893 probands within a 5-year period. Of them, inv dup(15) was confirmed in 25 children (46.3%) by FISH analysis. The PW/ASCR probes were used to clarify the size and DNA composition of the markers. Patients with inv dup(15) chromosomes, containing only the heterochromatin or little euchromatin of the proximal 15q (i.e., pter-->q11:q11-->pter) may have a rather mild or nearly normal phenotype (group 1). Only one patient had some features suggestive of Angelman syndrome, but was considered to be a result of deleted (15)(q12) in the chromosome 15 homologue. Additional copies within D15S11 through GABRB3 (15q11.2-13) resulted in an abnormal phenotype which involved mental and developmental delay but was different from the classical phenotype of PW/AS (groups 2, 3). Signs of autistic behavior did occur in each group. FISH combined with microsatellite analyses showed that the marker was often of maternal origin in de novo cases (n = 12, 86%), or inherited from the mother in only one familial case. Down-inv dup(15) was mentioned in two cases. Unusual features including diaphragmatic eventration, hyperlaxity of joints, arachnodactyly, brain atrophy, epilepsy (particularly infantile spasm), ataxia, genital abnormalities, and cleft lip/palate were noted in those patients. This observation expands the range of phenotypic expression associated with this relatively common ESAC. CONCLUSION: Marked phenotypic diversities exist in children with inv dup(15), dependent upon the size or genetic composition of the markers, degree of mosaicism, parental origin and familial occurrence or not. Patients with a larger inv dup(15) marker chromosome including the PW/ASCR may have a higher risk of abnormalities, but not the typical Prade-Willi/Angelman syndrome phenotype.

Adolescent↗
PubMed2003

Expression of Cdx2 and the phenotype of advanced gastric cancers: relationship with prognosis.

PURPOSE: The clinicopathologic significance of the phenotype and Cdx2 expression has hitherto remained unclear in gastric cancers. In the present study, we therefore examined the correlation between prognosis, phenotype, and Cdx2 expression in advanced cases. METHODS: We evaluated 177 advanced gastric carcinomas histologically and phenotypically. The expression of Cdx2 was also assessed by immunohistochemistry. RESULTS: The lesions were phenotypically divided into 32 gastric (G type), 36 gastric and intestinal mixed (GI type), 53 intestinal (I type), and 56 null (N type) types, independent of the histological classification. Cdx2 nuclear staining demonstrated a close relation to intestinal phenotypic expression, not with the histological classification. Kaplan-Meier analysis of Cdx2 expression and the phenotype showed that the Cdx2 positive groups had a significantly better outcome than the negative ones (P=0.0013), and the patients with GI type cancers had significant better survival than those with N type (P=0.0052). CONCLUSIONS: Our results suggest that Cdx2 is a useful prognostic marker. In addition, advanced gastric cancers with both intestinal and gastric phenotypic expression have a relatively good prognosis. Combined evaluation of gastric and intestinal epithelial cell markers, including Cdx2, is clinically useful to predict outcome in patients with advanced neoplasm of the stomach.

Aged↗