PubMed Health⌕ Search

Biomedical subjects

G Tachdjian

Publications and source records attributed to G Tachdjian.

At least 19 recordsLinked to original sources
PubMed2000

Analysis of uncultured amniocytes by comparative genomic hybridization: a prospective prenatal study.

Comparative genomic hybridization (CGH) is a new molecular cytogenetic technique which can detect and map whole and partial aneuploidies throughout a genomic specimen DNA without culturing specimen cells. Thus, CGH may be used as a comprehensive and rapid screening test in prenatal unbalanced chromosomal abnormalities detection. We report the results of the first prospective study to evaluate the use of the CGH technique on uncultured amniocytes. Seventy-one amniotic fluid samples, obtained by transabdominal amniocentesis between the 14th and 35th weeks of gestation, were simultaneously investigated using CGH and conventional cytogenetics. Amniocentesis were done for advanced maternal age (21.1%), fetal ultrasound anomalies (73.3%) and high level of biochemical markers in maternal serum (5.6%). Sixty-six (93%) informative results were generated on a total of 71 analysed specimens. Fifty-nine samples were reported as disomic for all autosomes with a normal sex chromosome constitution using CGH and conventional cytogenetics. Among them, three pericentromeric chromosomal inversions were undetected by CGH analysis. Seven numerical aberrations were characterized, including one case of trisomy 13, one case of trisomy 18 and five cases of trisomy 21. Advantages and limitations of CGH for a rapid prenatal screening of unbalanced chromosomal aberrations are discussed.

Amniocentesis↗
PubMed1999

De novo inverted duplication 9p21pter involving telomeric repeated sequences.

We report on clinical and cytogenetic findings in a boy with partial 9p duplication, dup(9)(p21pter). Clinical manifestations included facial and hand anomalies and mental retardation. Fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) were used to characterize further and confirm the conventional banding data. Investigation by FISH using whole chromosome 9 paint probe showed that the additional material was derived from chromosome 9. Using CGH, a region of gain was found in the chromosome segment 9p21pter. YACs and telomeric probes confirmed the duplicated region. Using the all-human telomeric sequences probe, intrachromosomal telomeric signal was noted on the short arm of the abnormal chromosome 9. Mechanism of formation of the duplication, including intrachromosomal telomeric sequences, is discussed.

Abnormalities, Multiple↗
PubMed1999

[Contribution of molecular cytogenetics to the diagnosis of chromosome anomalies].

UNLABELLED: MOLECULAR CYTOGENETICS: New fluorescent in situ hybridization (FISH) techniques have been developed using fluorescent non-radioactive DNA probes. FISH: Based on the complementary of nucleotides FISH enables visualization and localization of a DNA fragment on chromosomes by hybridizing the complementary DNA sequence, the probe. Many types of tissues can be analyzed, for example hematopoietic cells in blood or bone marrow, amniotic cells, trophoblasts, fibroblasts, gamete or tumoral cells. APPLICATIONS: Molecular cytogenetics can be used to characterize chromosome anomalies in many fields of cytogenetics (constitutional studies, prenatal diagnosis, hematology, oncology).

Chromosome Aberrations↗
PubMed1998

[Genomic imprinting].

UNLABELLED: AN EXCEPTION TO THE RULE: For certain genes, alleles are expressed differently depending on whether they originate from the maternal or paternal genome. This is called the parental imprinting. The parental imprinting plays an important role in development and a dysregulation can lead to various disease states. Loss of the parental imprinting or its alteration is implicated in certain genetic diseases and cancers. When the process is altered, two homologous chromosomes may come from the same parent, a situation termed uniparental disomy. GENETIC DISEASE IN MAN: Several genetic diseases in man are known to be related to the parental imprinting. Willi-Prader disease, Angelman disease and Beckwith-Wiedemann disease are the most extensively studied. MECHANISMS: Some of the underlying mechanisms are known, but several points concerning the parental imprinting remain to be elucidated, particularly the precise nature of the molecular mechanisms and the identification of the genes controlling this genetic process.

Angelman Syndrome↗
PubMed1998

Altered patterns of DNA methylation on chromosomes from leukemia cell lines: identification of 5-methylcytosines by indirect immunodetection.

An immunodetection technique has been developed to map with high resolution the methylated sites of human chromosomes. We have used this method to define the methylated areas of chromosomes from normal donors and from leukemia cell lines. The chromosomes were exposed for a short time to UV light to induce mild denaturation. The methylated sites were detected in situ by using monoclonal antibodies against 5-methylcytosine (prepared in mouse), and fluorescein-conjugated antimouse immunoglobulins. The chromosomes from normal cells exhibited a fluorescent pattern with RCT banding, although some differences from previously reported patterns could be detected. With this method we have been able to show the presence of two types of R-bands: High fluorescence R-band (HFR) and low fluorescence R-band (LFR). Chromosomes from leukemia cell lines exhibited low global staining with disrupted RCT banding of the chromosomes. The decreased level of the methylation status of the chromosomes from leukemia cells was confirmed by detection of 5-methylcytosines on total immobilized DNA. Thus, we have shown that this method can be used to determine the methylated status of chromosomes and, in turn, to map not only the structural (banding) but also the functional (methylation status) properties of the different chromosome domains in normal and pathologic human cells.

5-Methylcytosine↗
PubMed1998

Identification and characterization of a de novo partial trisomy 10p by comparative genomic hybridization (CGH).

We report the characterization of a de novo unbalanced chromosome rearrangement by comparative genomic hybridization (CGH) in a 15-day-old child with hypotonia and dysmorphia. We describe the combined use of CGH and fluorescence in situ hybridization (FISH) to identify the origin of the additional chromosomal material on the short arm of chromosome 6. Investigation with FISH revealed that the excess material was not derived from chromosome 6. Identification of unknown unbalanced aberrations that could not be identified by traditional cytogenetics procedures is possible by CGH analysis. Visual analysis of digital images from CGH-metaphase spreads revealed a predominantly green signal on the telomeric region of chromosome 10p. After quantitative digital ratio imaging of 10 CGH-metaphase spreads, a region of gain was found in the chromosome band 10p14-pter. The CGH finding was confirmed by FISH analysis, using a whole chromosome 10 paint probe. These results show the usefulness of CGH for a rapid characterization of de novo unbalanced translocation, unidentifiable by karyotype alone.

Adolescent↗
PubMed1998

Comparative genomic hybridization: technical development and cytogenetic aspects for routine use in clinical laboratories.

Comparative genomic hybridization (CGH) offers a new global approach for detection of chromosomal material imbalances of the entire genome in a single experiment without cell culture. In this paper, we discuss the technical development and the cytogenetic aspects of CGH in a clinical laboratory. Based only on the visual inspection of CGH metaphase spreads, the correct identification of numerical and structural anomalies are reported. No commercial image analysis software was required in these experiments. We have demonstrated that this new technology can be set up easily for routine use in a clinical cytogenetics laboratory.

Aneuploidy↗
PubMed1998

Comparison of comparative genomic hybridization with conventional karyotype and classical fluorescence in situ hybridization for prenatal and postnatal diagnosis of unbalanced chromosome abnormalities.

The comparative genomic hybridization (CGH) technique was initially used for detection of chromosomal imbalances in tumor cells. CGH can also be used as a supplementary method to karyotypic analysis in clinical cytogenetic cases. In order to evaluate CGH usefulness in prenatal and postnatal analysis of whole chromosome and segmental aneusomies, we investigated 13 clinical samples from blood, cultured chorionic villi, cultured amniotic fluids and uncultured amniotic fluids. These specimens, initially analyzed by conventional cytogenetics, included 5p monosomy, 9p duplication, add 6p, unbalanced translocation between chromosomes 5 and 10, mosaic tetrasomy 12p (50%), unbalanced (X;X) translocation and Prader-Willi deletion (15q11-13). In addition, six numerical chromosome aberrations (tetrasomy X, trisomies 13, 18, 21 and monosomy X) were analysed. All the chromosomal abnormalities, except the Prader-Willi deletion, were correctly detected by CGH. Here, we have demonstrated that the CGH technique is an alternative to classical fluorescence in situ hybridization using specific probes for detection of the unbalanced chromosomal aberrations in prenatal and postnatal diagnosis and could be used for rapid prenatal screening for unbalanced aberrations.

Amniotic Fluid↗
PubMed1994

Evaluation of X, Y, 18, and 13/21 alpha satellite DNA probes for interphase cytogenetic analysis of uncultured amniocytes by fluorescence in situ hybridization.

The major aneuploidies diagnosed prenatally involve the autosomes 13, 18, and 21, and sex chromosomes. Fluorescence in situ hybridization (FISH) allows rapid analysis of chromosome copy number in interphase cells. This prospective study evaluated the use of four commercially available centromeric DNA probes (DXZ1, DYZ1, D18Z1, and D13Z1/D21Z1) for direct analysis of uncultured amniocytes. One hundred and sixteen amniotic fluid samples were analysed by FISH and standard cytogenetics. This evaluation demonstrated that FISH with X, Y, and 18 alpha satellite DNA probes could accurately and rapidly detect aneuploidies involving these chromosomes and could be used in any prenatal clinical laboratory. In contrast, the 13/21 alpha satellite DNA probe hybridizing both chromosomes 13 and 21 was unreliable for prenatal diagnosis in uncultured amniocytes.

Amniotic Fluid↗
PubMed1994

Localization of the human coproporphyrinogen oxidase gene to chromosome band 3q12.

The human gene encoding coproporphyrinogen oxidase is the defective gene in hereditary coproporphyria. This gene was mapped to chromosome band 3q12 using fluorescent in situ hybridization. The chromosomal localization was confirmed by cosegregation of the human gene with chromosome 3 in a panel of human/rodent somatic hybrids.

Animals↗
PubMed1993

A simple method for prenatal diagnosis of trisomy 21 on uncultured amniocytes.

Prenatal diagnosis of trisomy 21 would be easier if fluorescence in situ hybridization (FISH) could be applied to interphase nuclei. Therefore, we prepared a chromosome-21-specific probe by in vitro enzymatic amplification of inter-Alu sequences from YAC clones previously localized to this chromosome. This probe was used for FISH on 22 uncultured amniocyte samples. An easy, rapid, and safe technique is proposed for the prenatal diagnosis of trisomy 21.

Amniocentesis↗
PubMed1992

The Wolf-Hirschhorn syndrome in fetuses.

Wolf-Hirschhorn syndrome (WHS) with partial deletion of the short arm of chromosome 4 has been exceptionally diagnosed in fetuses. We report prenatal diagnosis of five cases of monosomy 4p. The fetuses were karyotyped for severe intrauterine growth retardation (IUGR) diagnosed on routine ultrasound (US). In addition, cleft-lip and palate and diaphragmatic hernia respectively were found in two cases. The quantity of amniotic fluid was normal in all cases. At autopsy, the fetuses showed the typical craniofacial dysmorphy but without microcephaly. Major renal hypoplasia was the only constant visceral anomaly. Midline fusion defects were observed in all the fetuses, ranging from minor abnormalities such as scalp defect, hypertelorism, pulmonary isomerism, common mesentery, hypospadias and sacral dimple, to cleft palate, corpus callosum agenesis, ventricular septal defect, and diaphragmatic hernia. On post-mortem X-rays, a delayed bone age was always observed. All the placentae were hypotrophic, and two exhibited vascular lesions, although there was no maternal hypertension. Chromosomal studies showed that the breakpoints were within the 4p16 band in three cases, the 4p15 band in one case, and the 4p14 band in one case. The deletion was de novo in four cases, and resulted from a paternal translocation in one case. This study emphasizes the importance of karyotyping all fetuses with IUGR, especially when the quantity of amniotic fluid is normal, and suggests the possibility of recognizing on US the particular phenotype of WHS in utero.

Abnormalities, Multiple↗
PubMed1992

Detection of 47,XYY trophoblast fetal cells in maternal blood by fluorescence in situ hybridization after using immunomagnetic lymphocyte depletion and flow cytometry sorting.

Fluorescence in situ hybridization (FISH) allows to diagnose aneuploidy in uncultured interphase nuclei. This rapid method of chromosomal analysis associated with cell-sorting techniques was realized on 47,XYY fetal cells isolated from maternal blood. Trophoblast cells were sorted by combining immunomagnetic removal of maternal lymphocytes and flow cytometry sorting using antitrophoblast monoclonal antibodies. Cells were sorted directly on slides and analyzed by FISH with a Y-centromeric probe. Among 1,387 examinable nuclei, 59 (4.25%) showed one single or two Y-specific domains.

Aneuploidy↗
PubMed1992

Unbalanced karyotype due to adjacent 1 segregation of t(11;22)(q23.3;q13.2).

The 11q;22q translocations, whatever the breakpoints may be, are of particular interest because of their propensity to 3:1 segregation of the chromosomes at meiosis I. Until now, no unbalanced karyotype resulting from 2:2 adjacent segregation was published among offspring of 11q;22q translocation carriers. The authors report the case of an unbalanced karyotype due to adjacent 1 segregation of a maternal translocation (11;22)(q23.3;q13.2). The proband's karyotype was 46,XX,-22,+der(22)(11;22)(q23.3;q13.2)mat. This finding demonstrates that adjacent 1 segregation is possible in t(11;22) with breakpoints at 11q23 and 22q13, and can lead to birth of viable infants.

Abnormalities, Multiple↗
PubMedDate not supplied

Analysis of the 5' flanking sequence of the G gamma globin gene by denaturing gradient gel electrophoresis confirms the heterogeneity of the Bantu beta S haplotype.

The GC-->TT polymorphism recently described at positions -1106 and -1105 in the 5' flanking region of the G gamma globin gene for the Bantu beta S haplotype was analysed by denaturing gradient gel electrophoresis. We studied 108 beta S chromosome and 122 beta A chromosomes. The TT sequence was found as follows: in all of 80 chromosomes bearing the Bantu beta S haplotype with the 6-bp deletion -400 nt from the G gamma gene in 3 out of 5 Bantu beta S chromosomes without the deletion, in 1 out of 122 beta A chromosomes from different ethnic origins but in none of 23 beta S chromosomes bearing the Senegal, Benin or Cameroon haplotypes. These results confirm the heterogeneity of the Bantu beta S haplotype and allow a tentative evolutionary sequence for the different alleles at this locus to be presented.

Anemia, Sickle Cell↗