Xp21 microdeletion syndrome is associated with variable size Xp21 deletions that usually include the glycerol kinase locus. The clinical phenotypes we studied in this chromosome region include: Xpter – Åland Island eye disease (AIED)... more
Xp21 microdeletion syndrome is associated with variable size Xp21 deletions that usually include the glycerol kinase locus. The clinical phenotypes we studied in this chromosome region include: Xpter – Åland Island eye disease (AIED) ‐adrenal hypoplasia (AH) ‐glycerol kinase (GKD) ‐Duchenne muscular dystrophy (DMD) ‐retinitis pigmentosa (RP) ‐ornithine transcarbamylase (OTC) ‐centromere. In a compilation of 18 individuals in 14 families with the AH, GKD, and DMD loci deleted, 17 were male and all were developmentally delayed. In contrast, we report mentally retarded female carriers in two Xp21 deletion syndrome families with DMD, GKD, and AH in affected males. In the first family with normal karyotypes, a submicroscopic deletion was associated with DMD in the retarded male and with retardation in carrier females. In the second family an X chromosome with a cytogenetically deleted Xp21 distal to the OTC and RP genes segregated in the affected male and retarded female carriers. DNA an...
Research Interests:
Research Interests:
Chromosome analysis is the single most frequent test used in laboratory prenatal diagnostic studies. I summarize the current status of the field, including diagnostic problems in the laboratory and the clinical problems associated with... more
Chromosome analysis is the single most frequent test used in laboratory prenatal diagnostic studies. I summarize the current status of the field, including diagnostic problems in the laboratory and the clinical problems associated with communicating unexpected laboratory findings. I explore the effect of molecular genetics on these issues and its possible future effects on the entire practice of prenatal diagnosis as it relates to the risk for chromosome nondisjunction (trisomy). I also discuss the use of cytogenetic analysis in the prenatal diagnosis of certain inherited genetic diseases.
Research Interests:
A family has been identified in which an interstitial, apparently unbalanced deletion of the short arm of chromosome 5 could be traced through six individuals in 3 generations. Remarkably, all of the individuals with the deletion are... more
A family has been identified in which an interstitial, apparently unbalanced deletion of the short arm of chromosome 5 could be traced through six individuals in 3 generations. Remarkably, all of the individuals with the deletion are completely asymptomatic and show no physical or mental abnormalities. The deletion was confirmed at the molecular level by identifying DNA probes that mapped within the deleted portion of chromosome 5. Through the use of somatic cell hybrids and quantitative Southern blots, we demonstrated that these individuals do indeed have an unbalanced deletion and are haploid for several million base pairs of DNA in 5p14 without showing any discernable phenotype.
Research Interests:
An abnormally great amount of exhange between both sister and nonsister-but-homologous chromatids is a highly characteristic feature of cultured blood lymphocytes from individuals with Bloom's syndrome. However, a population of... more
An abnormally great amount of exhange between both sister and nonsister-but-homologous chromatids is a highly characteristic feature of cultured blood lymphocytes from individuals with Bloom's syndrome. However, a population of lymphocytes which exhibit a normal amount of exchange can be detected in the blood of some individuals with this syndrome. This coexistence of cells with a greatly increased number of sister-chromatid exchanges and others with a normal number results in a phenotypic dimorphism, in apparent contradiction to the autosomal recessive mode of inheritance of the syndrome.
Research Interests:
Research Interests:
Uniparental isodisomy resulting from the simultaneous presence of isochromosomes of the p and q arms of a chromosome and absence of a normal homologue is an exceptionally rare event. We have observed a growth-retarded female infant in... more
Uniparental isodisomy resulting from the simultaneous presence of isochromosomes of the p and q arms of a chromosome and absence of a normal homologue is an exceptionally rare event. We have observed a growth-retarded female infant in whom the normal chromosome 7 homologues were replaced by what appeared cytogenetically to be isochromosomes of 7p and 7q. Polymorphic microsatellite loci spanning the length of 7p and 7q were analyzed in the proband and her parents to ascertain the parental origin and extent of heterozygosity of the proband's rearranged chromosomes. These studies demonstrated that the 7p alleles of the proband were derived only from the father, the 7q alleles were derived only from the mother, and there was homozygosity for all chromosome 7 loci analyzed. The mechanisms leading to the formation of the proband's isochromosomes could reflect abnormalities of cell division occurring at meiosis, postfertilization mitosis, or both. We believe that the present case may result from incomplete mitotic interchange in the pericentromeric regions of chromosome 7 homologues, with resolution by sister-chromatid reunion in an early, if not first, zygotic division. Phenotypically, our proband resembled three previously reported cases of maternal isodisomy for chromosome 7, suggesting that lack of paternal genes from 7q may result in a phenotype of short stature and growth retardation.
Research Interests: Genetics, Biology, Fathers, Medicine, Cell Division, and 15 moreBiological Sciences, Mitosis, Humans, Haplotypes, Female, Dwarfism, Growth Inhibition, Chromosome Disorders, Base Sequence, Growth Retardation, Chromosome Banding, Molecular Sequence Data, microsatellite loci, Chromosome aberrations, and Medical and Health Sciences
Research Interests:
Research Interests:
Down syndrome (DS) is a major cause of mental retardation and heart disease. Although it is usually caused by the presence of an extra chromosome 21, a subset of the diagnostic features may be caused by the presence of only band 21q22. We... more
Down syndrome (DS) is a major cause of mental retardation and heart disease. Although it is usually caused by the presence of an extra chromosome 21, a subset of the diagnostic features may be caused by the presence of only band 21q22. We now present evidence that significantly narrows the chromosomal region responsible for several of the phenotypic features of DS. We report a molecular and cytogenetic analysis of a three-generation family containing four individuals with clinical DS as manifested by the characteristic facial appearance, endocardial cushion defect, mental retardation, and probably dermatoglyphic changes. Autoradiograms of quantitative Southern blots of DNAs from two affected sisters, their carrier father, and a normal control were analyzed after hybridization with two to six unique DNA sequences regionally mapped on chromosome 21. These include cDNA probes for the genes for CuZn-superoxide dismutase (SOD1) mapping in 21q22.1 and for the amyloid precursor protein (APP) mapping in 21q11.2-21.05, in addition to six probes for single-copy sequences: D21S46 in 21q11.2-21.05, D21S47 and SF57 in 21q22.1-22.3, and D21S39, D21S42, and D21S43 in 21q22.3. All sequences located in 21q22.3 were present in three copies in the affected individuals, whereas those located proximal to this region were present in only two copies. In the carrier father, all DNA sequences were present in only two copies. Cytogenetic analysis of affected individuals employing R and G banding of prometaphase preparations combined with in situ hybridization revealed a translocation of the region from very distal 21q22.1 to 21qter to chromosome 4q. Except for a possible phenotypic contribution from the deletion of chromosome band 4q35, these data provide a molecular definition of the minimal region of chromosome 21 which, when duplicated, generates the facial features, heart defect, a component of the mental retardation, and probably several of the dermatoglyphic changes of DS. This region may include parts of bands 21q22.2 and 21q22.3, but it must exclude the genes S0D1 and APP and most of band 21q22.1, specifically the region defined by S0D1, SF57 and D21S47.
Research Interests:
Research Interests:
Research Interests:
While Barts hydrops is predicted when all 4 α globin genes are absent or non functional, hydrops has rarely been described with a hemoglobin H (Hb H) genotype. Hb H disease has a varied hematologic phenotype ranging from asymptomatic to... more
While Barts hydrops is predicted when all 4 α globin genes are absent or non functional, hydrops has rarely been described with a hemoglobin H (Hb H) genotype. Hb H disease has a varied hematologic phenotype ranging from asymptomatic to transfusion dependant. The severest clinical expression is non immune hydrops and may result in fetal demise. The commonest form of Hb H disease is deletional-type. This occurs when there is deletion of α2 and α1 genes in cis and deletion of either α2 or α1 in trans. The less frequent type, but clinically more severe, is non-deletional. This is usually due to a mutation in either α2 or α1 in cis and a deletion of both α2 and α1 in trans. There are rare reports of non-deletional Hb H due to homozygous α2 mutations without any α1 deletions or mutations. Heretofore, there have been no reports of hydrops with homozygous hemoglobin Constant Spring (Hb CS). A 31-year-old Laotian woman presented at 22 weeks with polyhydramnios. Besides this, the pregnancy w...
Research Interests:
Research Interests:
Chromosome analysis is the single most frequent test used in laboratory prenatal diagnostic studies. I summarize the current status of the field, including diagnostic problems in the laboratory and the clinical problems associated with... more
Chromosome analysis is the single most frequent test used in laboratory prenatal diagnostic studies. I summarize the current status of the field, including diagnostic problems in the laboratory and the clinical problems associated with communicating unexpected laboratory findings. I explore the effect of molecular genetics on these issues and its possible future effects on the entire practice of prenatal diagnosis as it relates to the risk for chromosome nondisjunction (trisomy). I also discuss the use of cytogenetic analysis in the prenatal diagnosis of certain inherited genetic diseases.
Research Interests:
Uniparental isodisomy resulting from the simultaneous presence of isochromosomes of the p and q arms of a chromosome and absence of a normal homologue is an exceptionally rare event. We have observed a growth-retarded female infant in... more
Uniparental isodisomy resulting from the simultaneous presence of isochromosomes of the p and q arms of a chromosome and absence of a normal homologue is an exceptionally rare event. We have observed a growth-retarded female infant in whom the normal chromosome 7 homologues were replaced by what appeared cytogenetically to be isochromosomes of 7p and 7q. Polymorphic microsatellite loci spanning the length of 7p and 7q were analyzed in the proband and her parents to ascertain the parental origin and extent of heterozygosity of the proband's rearranged chromosomes. These studies demonstrated that the 7p alleles of the proband were derived only from the father, the 7q alleles were derived only from the mother, and there was homozygosity for all chromosome 7 loci analyzed. The mechanisms leading to the formation of the proband's isochromosomes could reflect abnormalities of cell division occurring at meiosis, postfertilization mitosis, or both. We believe that the present case m...
Research Interests: Genetics, Biology, Fathers, Medicine, Cell Division, and 15 moreBiological Sciences, Mitosis, Humans, Haplotypes, Female, American, Dwarfism, Growth Inhibition, Chromosome Disorders, Base Sequence, Growth Retardation, Chromosome Banding, microsatellite loci, Chromosome aberrations, and Medical and Health Sciences
Dividing cells from persons with Bloom's syndrome, an autosomal recessive disorder of growth, exhibit increased numbers of chromatid breaks and rearrangements. A highly characteristic feature of the chromosome instability in this... more
Dividing cells from persons with Bloom's syndrome, an autosomal recessive disorder of growth, exhibit increased numbers of chromatid breaks and rearrangements. A highly characteristic feature of the chromosome instability in this syndrome is the tendency for exchanges to occur between chromatids of homologous chromosomes at homologous sites. In the present experiments, a cytogenetic technique by which the sister chromatids of a metaphase chromosome are stained differentially has been used to demonstrate a striking and possibly specific, but hitherto unrecognized, increase in the frequency with which sister chromatids also exchange segments. The cells were grown in bromodeoxyuridine and stained with 33258 Hoechst and Giemsa. Whereas phytohemagglutinin-stimulated lymphocytes from normal controls had a mean of 6.9 sister chromatid exchanges per metaphase (range 1-14), those from persons with Bloom's syndrome had a mean of 89.0 (range 45-162). Normal frequencies of sister chroma...
Research Interests:
Chorionic villus sampling (CVS) has emerged as a first trimester alternative to amniocentesis for the prenatal detection of genetic disorders. We report our experience in 600 consecutive CVS procedures to better delineate the safety,... more
Chorionic villus sampling (CVS) has emerged as a first trimester alternative to amniocentesis for the prenatal detection of genetic disorders. We report our experience in 600 consecutive CVS procedures to better delineate the safety, efficacy and reliability of this new method of prenatal diagnosis. Adequate samples were obtained at the initial visit in 97 per cent of the cases, and successful cultures were established in 98.7 per cent of these patients. Chromosome abnormalities were detected in 5.9 percent of those pregnancies tested because of advanced maternal age (greater than or equal to 35 years). A discrepancy between the villus karyotype and that of the fetus was found in 2.0 per cent of cases, and most commonly consisted of mosaicism in the villus sample for a chromosomal abnormality that was not found in fetal samples. The risk of spontaneous abortion following the procedure was 6.3 per cent. We conclude that chorionic villus sampling is an acceptably safe and reliable procedure, but further investigation is needed before it can become an established technique in prenatal diagnosis.
Research Interests: Obstetrics, Medicine, Abortion, Pregnancy, Humans, and 14 moreFemale, Karyotyping, High risk pregnancy, Amniocentesis, Clinical Sciences, Trisomy 21, Maternal Age, Prenatal Diagnosis, Fetus, Chromosome Disorders, Mosaicism, Chorionic villus sampling, Chromosome aberrations, and Paediatrics and reproductive medicine
Research Interests:
Research Interests: Genetics, Human Genetics, Complementary and Alternative Medicine, Biology, Medicine, and 13 moreGene Mapping, Cell line, Humans, Female, Nucleic acid hybridization, Male, Centimorgan, Pedigree, Genetic linkage analysis, Charcot Marie Tooth Disease, Fc Receptor, Linkage Analysis, and Paediatrics and reproductive medicine
Human sperm chromosome complements were examined to assess the possibility that the conceptions of two children with the same chromosomal defect, del(13)(q22q32), from chromosomally normal parents were the result of a paternal germ cell... more
Human sperm chromosome complements were examined to assess the possibility that the conceptions of two children with the same chromosomal defect, del(13)(q22q32), from chromosomally normal parents were the result of a paternal germ cell mosaicism. Analysis of 216 complements, both by quinacrine banding and by measuring the relative length of chromosome 13, showed no unusual subpopulation of 13s; this decreased the likelihood of a paternal origin of the deletion. Sperm chromosomal analysis is a useful adjunct to available techniques in clinical genetics. When counseling cases involving either structural or numerical de novo chromosome abnormality, it is of importance to discuss the possibility of germ cell line mosaicism as well as to offer prenatal diagnosis for subsequent pregnancies.
Research Interests:
ft::fct����� : : : : : : : :::: : : : : : : : : : : : ::: : :: : :: : : : : : : : : : : : : : : :: : :: : : : : : : : : : : : :: : : : : : : : : : : : ::: : : : De novo trans locations . . . . . . . . . . . . . . . . . . . . . . . . . . .... more
ft::fct����� : : : : : : : :::: : : : : : : : : : : : ::: : :: : :: : : : : : : : : : : : : : : :: : :: : : : : : : : : : : : :: : : : : : : : : : : : ::: : : : De novo trans locations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . , . . . . . . . . . . . . . Prenatal Diagnosis of Genetic Diseases with Cytogenetic Manifestations . . . . . . . . . . .. . . Fragile (X)-linked mental retardation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chromosome breakage syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Roberts syndrome _________ . . ____________ . . __________ . __________ .. .. _______ . . __ . _ _ _____ . . . _ _ . _ BIOCHEMICAL AND MOLECULAR TECHNIQUES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . Direct Analysis of Abnormal Gene Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Disorders resulting from gene deletions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Disorders resulting from point mutations . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . Prenl!ta! Djagnosis by Linkage Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . LImitatIOns to use . . . . . . . . . . . . .. . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . .
Research Interests:
Fragile X [fra(X)] cell lines have been established from an expressing 46, XX amniocyte culture. The amniocyte cells were transformed by the addition of an origin defective pSV40 vector. Fra(X) expression was observed at a frequency of 3%... more
Fragile X [fra(X)] cell lines have been established from an expressing 46, XX amniocyte culture. The amniocyte cells were transformed by the addition of an origin defective pSV40 vector. Fra(X) expression was observed at a frequency of 3% in the parental amniocyte cell line, and the transformed clones expressed the fra(X) site at a frequency of 9–13%. These cell lines maintain the cytogenetic phenotype and can serve as positive controls for testing the efficacy of the inducing systems during prenatal diagnostic studies.
Research Interests:
The effect of advancing maternal age on the risk of death of fetuses with certain chromosome abnormalities has been tested by comparing their frequency at the time of chorionic villus sampling (CVS) with that at amniocentesis. The... more
The effect of advancing maternal age on the risk of death of fetuses with certain chromosome abnormalities has been tested by comparing their frequency at the time of chorionic villus sampling (CVS) with that at amniocentesis. The frequency of chromosome abnormalities among women whose sole risk factor for a chromosome abnormality was advanced maternal age (≥35 years old) was determined in a pooled group of 15,147 CVS cases, of whom > 1/3 were from the initial 7,500 CVS cases at the University of California, San Francisco, and compared with a pooled group of 74,851 amniocentesis cases collected from the literature. The frequency of trisomy 21 not only increased with advancing maternal age as expected, but the slope of the increase was about 25% greater in the CVS group than in the amniocentesis group (P = 0.08 for the difference in slopes by a logistic statistical model and P = 0.04 by a normit model). Similar patterns were seen for trisomies 18 and 13, but the P values for the d...
Research Interests:
The following guidelines were adopted by an Ad Hoc Committee convened at the Fourth International Workshop on the Fragile X Syndrome and X‐Linked Mental Retardation to establish minimum cytogenetic standards for the preparation and... more
The following guidelines were adopted by an Ad Hoc Committee convened at the Fourth International Workshop on the Fragile X Syndrome and X‐Linked Mental Retardation to establish minimum cytogenetic standards for the preparation and analysis of the fragile X chromosome. The intention of the committee was to develop and provide practical standards for the routine cytogenetic detection of the fragile X. The guidelines describe reasonable criteria for effective tissue culture methods for eliciting the Xq27.3 fragile site in vitro and for the analysis of such chromosome preparations.
Research Interests:
Each of several cultures of Werner's syndrome (WS) fibroblasts and lymphoblasts examined was found to be composed of one or several clones of cells with mutated chromosome complements. Two "sister" fibroblasts cell lines (FCLs) that were... more
Each of several cultures of Werner's syndrome (WS) fibroblasts and lymphoblasts examined was found to be composed of one or several clones of cells with mutated chromosome complements. Two "sister" fibroblasts cell lines (FCLs) that were derived from a mixture of explants cut from the same WS skin biopsy were found to have completely different rearranged chromosome complements. Daily observation of the skin explants from which these two sister FCLs were derived revealed not only that no more than a few fibroblasts ever migrated from a given explant but also that fibroblasts migrated from only a few of the explants. Two of three lymphoblastoid cell lines (LCLs), each probably developed as an independent clone from a different cell from the same WS blood sample, were mosaic, comprised of cells having both normal and rearranged chromosome complements. The third LCL studied, although nonmosaic, had a rearranged chromosome complement, but one that was completely different from those in the other two lines. Based on the observations described, hypotheses have been formulated to explain both the preponderance in long-term WS cultures of clones with mutated chromosome complements and the abbreviated lifespan characteristic of WS fibroblast cultures.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
The precise nature of the functional human centromeric sequences remains a matter of some controversy. Evidence has accumulated over the past several years that directly implicates alphoid repeats as a critical component. We report a... more
The precise nature of the functional human centromeric sequences remains a matter of some controversy. Evidence has accumulated over the past several years that directly implicates alphoid repeats as a critical component. We report a child with dysmorphic features consistent with the recently described small ring X syndrome, with a constitutional karyotype that addresses this issue. At 5 1/2 months, the patient was a small, hypotonic, delayed female with brachycephaly, a broad forehead, prominent nasal root, synophorous, small mouth, and cup-shaped ears with prominent lobules, as well as microcornea, and pendular nystagmus. Hand abnormalities included single palmar creases and short tapered fingers. In addition to mosaicism for a small ring chromosome derived from the proximal short arm of the X, the proband has, in all cells, a monocentric isochromosome for the long arm of the X. The karyotype is interpreted as 46,X,iso(Xq)/47,X,iso(Xq),r(Xp11cen). We present routine karyotypic and FISH analysis of the rearranged X chromosomes. We propose that the only mechanism consistent with this karyotype is that of a two-break rearrangement with one break bisecting a centromere in such a way as to retain functional centromeric activity in each of the separated regions. The second break, proximal in the short arm,more » allows for ring chromosome formation with the bisected centromere. The iso(Xq) arises by the classical mechanism of post-replication sister-reunion. The formation of two functional centromeres by a single break through the {open_quotes}parental{close_quotes} centromere indicates that the functional activity must be in a repeated component of the centromeric DNA and argues strongly against the requirement for any single gene in cis orientation.« less
Research Interests:
We previously reported the cloning and detailed analysis of the integrated hepatitis B virus sequences in a human hepatoma cell line. We report here the integration of at least one of hepatitis B virus at human satellite DNA sequences.... more
We previously reported the cloning and detailed analysis of the integrated hepatitis B virus sequences in a human hepatoma cell line. We report here the integration of at least one of hepatitis B virus at human satellite DNA sequences. The majority of the cellular sequences identified by this satellite DNA were organized as a multimeric composition of a 0.6-kilobase EcoRI fragment. This clone hybridized in situ almost exclusively to the centromeric heterochromatin of chromosomes 1 and 16 and to a lower extent to chromosome 2 and to the heterochromatic region of the Y chromosome. The immediate flanking host sequence appeared as a hierarchy of repeating units which were almost identical to a previously reported human satellite III DNA sequence.
Research Interests:
1955 Poster Board I-978 The detection of chromosome abnormalities in mature B-cell neoplasms by conventional cytogenetics remains difficult, mainly due to the low proliferative rate of mature lymphoid cells. The current FISH panel for... more
1955 Poster Board I-978 The detection of chromosome abnormalities in mature B-cell neoplasms by conventional cytogenetics remains difficult, mainly due to the low proliferative rate of mature lymphoid cells. The current FISH panel for chronic lymphocytic leukemia (CLL) is designed to detect some of the more common abnormalities of prognostic significance in CLL [i.e., del(6q), del(11q), +12, del(13q), del(17p)]. This CLL FISH panel has improved the detection rate of these markers by making it possible to obtain cytogenetic information from interphase cells; however, as it is limited to only these 5 markers, it cannot detect all abnormalities associated with CLL. More importantly, the impact of other chromosome abnormalities on prognosis and disease progression, with and without the presence of these 5 prognostic markers, is not known. CpG-oligodeoxynucleotides (ODNs) such as DSP30 activate cells of the immune system in a sequence-dependent manner and promote proliferation of CLL cel...
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Using a recombinant DNA probe, we have demonstrated the presence of residual 3.4-kilobase (kb) repeat sequences in a family with a Yq- chromosome. The heterochromatin of this Y variant was not readily detectable with conventional... more
Using a recombinant DNA probe, we have demonstrated the presence of residual 3.4-kilobase (kb) repeat sequences in a family with a Yq- chromosome. The heterochromatin of this Y variant was not readily detectable with conventional chromosome-banding techniques. These data suggest that the breakpoint of the deletion occurs at the heterochromatin region proximal to the euchromatin/heterochromatin junction.
Research Interests:
Each of several cultures of Werner's syndrome (WS) fibroblasts and lymphoblasts examined was found to be composed of one or several clones of cells with mutated chromosome complements. Two "sister" fibroblasts cell lines... more
Each of several cultures of Werner's syndrome (WS) fibroblasts and lymphoblasts examined was found to be composed of one or several clones of cells with mutated chromosome complements. Two "sister" fibroblasts cell lines (FCLs) that were derived from a mixture of explants cut from the same WS skin biopsy were found to have completely different rearranged chromosome complements. Daily observation of the skin explants from which these two sister FCLs were derived revealed not only that no more than a few fibroblasts ever migrated from a given explant but also that fibroblasts migrated from only a few of the explants. Two of three lymphoblastoid cell lines (LCLs), each probably developed as an independent clone from a different cell from the same WS blood sample, were mosaic, comprised of cells having both normal and rearranged chromosome complements. The third LCL studied, although nonmosaic, had a rearranged chromosome complement, but one that was completely different f...
Research Interests:
This paper describes the application of bivariate flow karyotyping to (1) classification of chromosomes isolated from cultures of cells taken by amniocentesis and (2) detection of numerical and structural aberrations. Chromosomes were... more
This paper describes the application of bivariate flow karyotyping to (1) classification of chromosomes isolated from cultures of cells taken by amniocentesis and (2) detection of numerical and structural aberrations. Chromosomes were isolated from primary cultures 2-5 wk after amniocentesis, stained with Hoechst 33258 and chromomycin A3, and analyzed using dual beam flow cytometry. Information about chromosome DNA content and DNA base composition was derived from the locations of the peaks in the flow karyotypes, each peak being produced by one or more chromosome types with similar DNA content and DNA base composition. Information about the relative frequency of each chromosome type was determined on the basis of the relative volume of the peak for that chromosome type. Cytogenetic information determined on the basis of flow karyotypes was compared with that obtained by visual analysis following G-banding. Variability among the peak means and volumes in flow karyotypes was determin...
Research Interests:
Research Interests:
Cytogenetic data are presented for 11 473 chorionic villus sampling (CVS) procedures from nine centres in the U.S. NICHD collaborative study. A successful cytogenetic diagnosis was obtained in 99.7 per cent of cases, with data obtained... more
Cytogenetic data are presented for 11 473 chorionic villus sampling (CVS) procedures from nine centres in the U.S. NICHD collaborative study. A successful cytogenetic diagnosis was obtained in 99.7 per cent of cases, with data obtained from the direct method only (26 per cent), culture method only (42 per cent), or a combination of both (32 per cent). A total of 1.1 per cent of patients had a second CVS or amniocentesis procedure for reasons related to the cytogenetic diagnostic procedure, including laboratory failures (27 cases), maternal cell contamination (4 cases), or mosaic or ambiguous cytogenetic results (98 cases). There were no diagnostic errors involving trisomies for chromosomes 21, 18, and 13. For sex chromosome aneuploidies, one patient terminated her pregnancy on the basis of non‐mosaic 47,XXX in the direct method prior to the availability of results from cultured cells. Subsequent analysis of the CVS cultures and fetal tissues showed only normal female cells. Other fa...
Research Interests: Medicine, Cytogenetics, Pregnancy, Humans, United States, and 15 moreFemale, Prenatal, Aneuploidy, Karyotyping, Amniocentesis, Clinical Sciences, Karyotype, Adult, Prenatal Diagnosis, Chromosome Disorders, Mosaicism, Predictive value of tests, Chorionic villus sampling, Chromosome aberrations, and Paediatrics and reproductive medicine
Research Interests:
ABSTRACT
Research Interests:
Research Interests: Molecular Biology, Flow Cytometry, Biology, Cell Cycle, Immunohistochemistry, and 15 moreMedicine, Biological Sciences, DNA, Humans, Human Molecular Genetics, Immunoprecipitation, Helicase, Telomere, Base Sequence, Enzyme Linked Immunosorbent Assay, Oligonucleotides, RecQ Helicases, Molecular Sequence Data, Medical and Health Sciences, and Cytogenetic analysis
A portion of the DNA within intact nuclei of a spontaneously transformed Chinese hamster ovary cell line (CHO-Kl) is relatively resistant to digestion by pancreatic deoxyribonuclease, as compared to nuclei from primary cultures of Chinese... more
A portion of the DNA within intact nuclei of a spontaneously transformed Chinese hamster ovary cell line (CHO-Kl) is relatively resistant to digestion by pancreatic deoxyribonuclease, as compared to nuclei from primary cultures of Chinese hamster ovary fibroblasts. Treatment of CHO-Kl cells with derivatives of 3',5' cyclic AMP (cAMP) under conditions which effect the reverse transformation (RT) of these cells, results in restoration of the increased sensitivity of their DNA to hydrolysis by pancreatic deoxyribonuclease, to the level characteristic of an untransformed, morphologically normal Chinese hamster fibroblast cell line. Dibutyryl (db-)cAMP and 8-bromo-cAMP (Br-cAMP) yielded similar results. The cAMP derivatives employed had no effect on the normal fibroblasts.
Research Interests:
Research Interests: Genetics, Autism, Intelligence, Medicine, Mental Retardation, and 15 moreHumans, Child, Male, Phenotype, Clinical Sciences, European, High Resolution, Chromosome, Learning Disabled, Comparative Genomic Hybridization, Array Comparative Genomic Hybridization, Autistic disorder, Attention deficit disorder with hyperactivity, Attention deficit hyperactivity disorder, and Chromosome deletion
Research Interests:
Research Interests: Obstetrics, Medicine, Screening, Cytogenetics, Pregnancy, and 15 moreHumans, Female, American, Amniocentesis, Trisomy 21, Gynecology, Prenatal Diagnosis, Chromosome Disorders, Mosaicism, Gestation, Chorionic villus sampling, Chromosome aberrations, Paediatrics and reproductive medicine, In Utero, and Diagnostic errors
Recently, we detected fra(X)(q27.3) in aminocyte cultures from female identical twins. The pregnant woman did not exhibit fra(X)(q27.3) in whole blood cultures but was the sister of 2 affected brothers. DNA marker analyses showed that she... more
Recently, we detected fra(X)(q27.3) in aminocyte cultures from female identical twins. The pregnant woman did not exhibit fra(X)(q27.3) in whole blood cultures but was the sister of 2 affected brothers. DNA marker analyses showed that she was a carrier of FRAXA. Amniotic fluid cultures (AFCs) from twins A and B exhibited the fragile X [fra(X)] chromosome, but the level of cytogenetic expression was very low in twin A's AFCs. DNA marker studies indicated both twins were carriers of FRAXA. Peripheral umbilical blood sample (PUBS) cultures exhibited fra(X)(q27.3) at a frequency of about 10% for both twins. DNA fingerprinting indicated that the twins were identical, confirming the clinical impression, with a very thin separating amniotic membrane. To our knowledge, this is the only report of prenatal fra(X)(q27.3) detection in female identical twins, and the second report of identical twin detection [Rocchi et al., 1985].We have diagnosed prenatally fra(X)(q27.3) in 5 female fetuses...