Twins of different races: choice or technical blunder.
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Ethics, Medical↗
Biomedical subjects
R S Verma
Publications and source records attributed to R S Verma.
Genomania of p53 protein in gastric cancer.
The role of oncogenes and tumor suppressor genes in the pathogenesis of gastric cancer has recently received considerable attention. p53 is a tumor suppressor gene that is essential in the cell cycle; it prevents G1/S phase transition, after exposure to ionizing radiation or DNA-damaging chemotherapy. This allows the cell to repair its DNA or, if the damage is irreversible, to elicit apoptotic cell death. p53 mutations are seen in many human tumors including gastric carcinoma. Evidence suggests that mutant p53 is associated with shorter life expectancy in gastric, breast, lung, and colorectal cancer. A number of studies have shown cellular resistance to chemotherapy in the presence of mutant p53. Currently, increasing interest has been devoted to the potential role of mutant p53 as a screening tool.
Apoptosis↗
Molecular characterization of 21p- variant chromosome.
Fortuitously, within a 1-month period, we were referred two individuals for routine cytogenetic amniocenteses involving one chromosome 21 from each patient, which had apparently lost the entire short arm and a major portion of the centromeric alphoid sequences in their amniocytes. Breakage may have occurred within alphoid sequences resulting in extreme variants. Variations of a similar nature were originally referred to as Christchurch (Ch1) chromosomes and have been wrongly determined to be abnormal. The 21p- chromosome variants were similar in both cases, though they are from unrelated individuals. These rare variants, whose origins were both maternal and have no clinical consequences, were characterized by the FISH-technique to provide a greater degree of certainty.
Amniocentesis↗
A de novo interstitial deletion of chromosome 15 band q25 as revealed by FISH-technique.
We report a new chromosomal finding in a 20 month-old girl. The minor clinical features included: moderate mental retardation, microcephaly, mild hypotonia and hypertelorism. Initially, what appeared to be a terminal deletion of the long arm of one chromosome 15 [15q26-->qter] was determined to be an interstitial deletion involving band 15q25 as revealed by FISH-technique, showing the presence of intact telomeric hybridization signals. The cytogenetic diagnosis was thus modified to 46,XX, del (15) (pter-->q24::q26--> qter). Nevertheless, the function of the enzyme telomerase should not be ignored, as healing could occur following such terminal deletions. Consequently, it will remain a difficult task to distinguish terminal deletions from those that are interstitial.
Chromosome Banding↗
Breakpoints in alpha, beta, and satellite III DNA sequences of chromosome 9 result in a variety of pericentric inversions.
Human chromosome 9 with a pericentric inversion involving the qh region is considered normal. It has probably evolved through breakage and reunion and is retained through mendelian inheritance without any apparent phenotypic consequences. Fluorescent in situ hybridisation (FISH) technique using alpha, beta, and satellite III DNA probes showed that the breakpoints are variable and can be localised in the alpha or in the satellite III and beta DNA regions or both. Three types of inversions are proposed which appear similar by CBG banding: pericentric inversions with two alphoid, one beta, and one satellite III hybridisation signals were classified as type A. Type B were those with two beta, one alpha, and one satellite III hybridisation signals, while type C was complex, and most likely involved two inversions, since two separate hybridisation signals were detected in each of the alphoid, beta satellite, and satellite III DNA regions. Based on eight cases, type A is likely to be the most frequent, but the frequencies, which at present appear non-random for these different types of inversions in the population, can only be estimated by studying a larger sample size. Inversion heteromorphisms may promote reshuffling of tandem arrays of DNA repeat sequences, thereby giving rise to new heteromorphic domains. Alternatively, the repetitive nature of the sequences lends to the structural variations observed within the inv(9) chromosomes (or any other abnormal chromosome that is the result of recombination between, or breakage within, repetitive DNA).
Chromosome Inversion↗
Role of protein tyrosine phosphorylation in H2O2-induced activation of endothelial cell phospholipase D.
Oxidant-induced activation of phospholipase D (PLD) in bovine pulmonary artery endothelial cells (BPAEC) is independent of protein kinase C and calcium. In the present study, the effects of tyrosine kinase and protein tyrosine phosphatase (PTPase) inhibitors on hydrogen peroxide (H2O2)-induced PLD activation and protein tyrosine phosphorylation were examined in BPAEC. Pretreatment of BPAEC with putative tyrosine kinase inhibitors genistein, tyrphostin, and herbimycin attenuated H2O2 (1 mM)-induced PLD activation. The inhibitory effect of the tyrosine kinase inhibitors was highly specific for H2O2-induced modulation and showed no effect on PLD activation mediated by 12-O-tetradecanoylphorbol 13-acetate or bradykinin. Furthermore, addition of H2O2 increased in a time-dependent manner tyrosine phosphorylation of several proteins (17-200 kDa), as determined by immunoblot analysis with antiphosphotyrosine antibodies. H2O2-mediated protein tyrosine phosphorylation preceded PLD activation, and a good correlation was observed on the effect of genistein in H2O2-induced PLD activation and protein tyrosine phosphorylation. Addition of vanadate, a phosphotyrosine phosphatase inhibitor, synergistically increased both PLD activation and protein tyrosine phosphorylation mediated by H2O2. Moreover, vanadate by itself had minimal effect on basal PLD activity in BPAEC; however, at 10 microM vanadate, an increase in protein tyrosine phosphorylation was observed. In addition to vanadate, phenylarsine oxide and diamide potentiated H2O2-induced PLD activation. These results suggest that tyrosine kinase activation may be involved in H2O2-induced PLD activation in vascular endothelial cells.
Animals↗
Parental origin of the extra chromosome 18 in Edwards syndrome.
Trisomy 18 (Edwards syndrome) is the second most common trisomy in human. The parental origin of the additional chromosome leading to meiotic errors is imperative to understand the etiology of trisomy 18. We compiled the data on 171 cases (table I) where meiotic error is provided. The paternal meiotic error occurred in 7% of the cases while in 93% of the cases nondisjunction took place in the mother. There were 28 cases (16%) where nondisjunction took place in meiosis I(MI), 53 cases (31%) in meiosis II (MII) and in 90 cases (53%) either the error was postzygotic mitosis or the dysfunctional stages could not be determined. The age distribution could be found in 119 cases (table II) and a conclusion could not be drawn as there were only 11 cases where paternal nondisjunction was noted.
Adolescent↗
Characterization of a derivative chromosome 17 by fish-technique.
We report a case with derivative chromosome 17 which could not be characterized by routine G-banding, since the additional material on 17q overlapped with chromosome bands 2q35 -->qter, 3p25-->pter, 4p15-->pter, 5q33-->qter, 7p15-->pter, 12p11.2-->pter, 14q24-->qter and 16q22-->qter. Therefore, whole chromosome paint and region specific probes were used to identify the abnormality by FISH-technique which revealed a 46,XY, der (17) t (4;17) (p15.2;q25) karyotype. The proband was partially trisomic for 4p15.2-->pter and monosomic for the distal 17q25-->qter regions. The major clinical features included: anti-mongoloid slanted palpebrae, coloboma of right iris, depressed nasal bridge, high arched palate, protruding tongue, micrognathia and small penis. The MRI of the brain revealed midly hypoplastic cerebellar vermis, and a normal septum pellucidum. The infant responded to therapy for hypoglycemia and was discharged under stable condition. Prior to cytogenetic evaluation the infant was not recognized as either "trisomy 4p syndrome" or "monosomy 17q syndrome".
Abnormalities, Multiple↗
Centromeric alphoid sequences are breakage prone resulting in pericentromeric inversion heteromorphism of qh region of chromosome 1.
Structural variations in the pericentromeric region of chromosome 1 are considered the norm. We characterized a chromosome 1 with an inversion by FISH-technique and suggested that the origin of pericentromeric heteromorphism is far more complex than previously suggested. It is postulated that similar to the centromeric alphoid DNA sequences of chromosome 9, chromosome 1 also possesses a "breakage prone" centromeric domain which may be a possible cause of such inversions involving the secondary constriction region.
Adult↗
Incidence of breakpoints in pericentric inversions of chromosome 4.
We report a new pericentric inversion of chromosome 4 in a female who has had two consecutive fetal losses during the first trimester conception. Cytogenetic findings with GTG-banding revealed a 46,XX,inv(4) (p13q13) karyotype in her peripheral blood cells. The breakpoint on the long arm is different from any other previously described case. A comprehensive bibliography of reported cases with pericentric inversion is also tabulated.
Chromosome Breakage↗
Characterization of a de novo t(Y;9) (q11.2;q22) by FISH technique.
A new case with a de novo translocation involving the long arms of chromosomes Y and 9 i.e. 46, X, t(Y;9) (q11.2;q22) was noted in a phenotypically normal male as revealed by GTG technique and subsequently confirmed using dual color whole chromosome painting probes. Since the Yq11.2 region was involved in the translocation the fecundity status of the individual has been questioned. Previous cases with (Y;autosomal) translocations have produced males with azoospermia, a variety of male gamete deformities and idiopathic sterility. The azoospermic factor (AZF) on the distal Yq11 band, which apparently controls spermatogenesis, may have been adversely affected due to a microdeletion, rearrangement or complete loss as a result of the translocation mechanism. Testicular histological and fertility tests of the proband at a postpubescent age will reveal the status. The sex determining region (SRY) on the Yp, which has been equated with the testis determining factor (TDF), is believed to be intact. Dual color whole chromosome painting probes, which served as an important adjunct to GTG banding, increased the degree of certainty for the characterization of the involved translocation. A concise review of balanced (Y ; autosome) translocation cases are annotated here.
Chromosomes, Human, Pair 9↗
Conservation of the Down syndrome critical region in humans and great apes.
A quarter century ago, a chimpanzee with trisomy 22 was reported to have the clinical manifestation of Down syndrome. The features of Down syndrome in human have been associated with chromosome 21 band q22.3. The recent availability of chromosome and loci specific probes has prompted us to utilize the human cosmid probe (D21S65) for the trisomy 21 region in the chromosomes of the chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla) and orangutan (Pongo pygmeus). Interestingly, the hybridization site for the Down syndrome region was found on the equivalent ape chromosome 22 in all three primates (the human equivalent of chromosome 21). Apparently, these results support the notion that the Down syndrome critical region of human chromosome 21 band q22.3 is conserved in great apes, which has displayed mongolism in a chimpanzee when present in triplicate conditions. Furthermore, other probes can be used as phylogenetic signals to enhance the understanding of human descent.
Animals↗
Amniotic-fluid cell growth and fetal aneuploidy.
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Amniotic Fluid↗
Human (Homo sapiens) and chimpanzee (Pan troglodytes) share similar ancestral centromeric alpha satellite DNA sequences but other fractions of heterochromatin differ considerably.
The euchromatic regions of chimpanzee (Pan troglodytes) genome share approximately 98% sequence similarity with the human (Homo sapiens), while the heterochromatic regions display considerable divergence. Positive heterochromatic regions revealed by the CBG-technique are confined to pericentromeric areas in humans, while in chimpanzees, these regions are pericentromeric, telomeric, and intercalary. When human chromosomes are digested with restriction endonuclease AluI and stained by Giemsa (AluI/Giemsa), positive heterochromatin is detected only in the pericentromeric regions, while in chimpanzee, telomeric, pericentromeric, and in some chromosomes both telomeric and centromeric, regions are positive. The DA/DAPI technique further revealed extensive cytochemical heterogeneity of heterochromatin in both species. Nevertheless, the fluorescence in situ hybridization technique (FISH) using a centromeric alpha satellite cocktail probe revealed that both primates share similar pericentromeric alpha satellite DNA sequences. Furthermore, cross-hybridization experiments using chromosomes of gorilla (Gorilla gorilla) and orangutan (Pongo pygmaeus) suggest that the alphoid repeats of human and great apes are highly conserved, implying that these repeat families were present in their common ancestor. Nevertheless, the orangutan's chromosome 9 did not cross-hybridize with human probe.
Animals↗
The genomic sequence for Prader-Willi/Angelman syndromes' loci of human is apparently conserved in the great apes.
Chromosomal changes through pericentric inversions play an important role in the origin of species. Certain pericentric inversions are too minute to be detected cytogenetically, thus hindering the complete reconstruction of hominoid phylogeny. The advent of the fluorescence in situ hybridization (FISH) technique has facilitated the identification of many chromosomal segments, even at the single gene level. Therefore the cosmid probe for Prader-Willi (PWS)/Angelman syndrome to the loci on human chromosome 15 [q11-13] is being used as a marker to highlight the complementary sequence in higher primates. We hybridized metaphase chromosomes of chimpanzee (PTR), gorilla (GGO), and orangutan (PPY) with this probe (Oncor) to characterize the chromosomal segments because the nature of these pericentric inversions remains relatively unknown. Our observations suggest that a pericentric inversion has occurred in chimpanzee chromosome (PTR 16) which corresponds to human chromosome 15 at PTR 16 band p11-12, while in gorilla (GGO 15) and orangutan (PPY 16) the bands q11-13 complemented to human chromosome 15 band q11-13. This approach has proven to be a better avenue to characterize the pericentric inversions which have apparently occurred during human evolution. "Genetic" divergence in the speciation process which occurs through "chromosomal" rearrangement needs to be reevaluated and further explored using newer techniques.
Angelman Syndrome↗
Clinical manifestations of trisomy 4p syndrome.
UNLABELLED: Trisomy 4p syndrome is a distinct clinical entity which was noted almost a quarter century ago by Wilson et al. [71] and later was delineated by Gonzalez and colleagues [29]. The variation in the length of duplicated segment usually associated with monosomy of other genetic material which has resulted in confusion and as a result a so-called 4p syndrome could not be recognized without cytogenetic analysis. We wish to draw the attention of clinicians to this subject by presenting the description of over 75 cases including one from our clinic and stress the point that molecular approaches are imperative to characterize this anomaly. After extensive review, it appears that patients retaining at least the distal two-thirds to the entire short arm share an overlapping phenotypic expression that constitutes pure trisomy 4p syndrome which includes prominent glabella, bulbous nose with flat or depressed nasal bridge, retrognathia, pointed chin, short neck with low hairline, enlarged ears with abnormal helix and antihelix, rocker-bottom feet with prominent heel. Arachnodactyly and camptodactyly. Molecular characterization of 4p is imperative. We have also included an extensive bibliography for clinicians who may find it useful as a single reference source for evaluating their future cases. CONCLUSION: The 4p-syndrome is a distinct entity but without cytogenetic evaluation, the syndrome can not be recognized.
Abnormalities, Multiple↗
Characterization of 7q--by FISH technique of a case with acute myelogenous leukemia evolving from agnogenic myeloid metaplasia.
We present a new case of acute myelogenous leukemia (AML) which evolved from agnogenic myeloid metaplasia (AMM). Routine cytogenetic techniques revealed a terminal deletion of one chromosome 7 (del (7) (q21)). When metaphases were hybridized with the 7q specific telomeric probe, a signal was detected at the distal q arm of the deleted chromosome 7 suggesting an interstitial deletion and the cytogenetic diagnosis was changed to 46,XY, del(7) (q21.1q36.2). Apparently, precise characterization of such deletions may have gone undetected, owing to the lack of technology, and deletions that have been previously regarded as terminal may very well be interstitial. Undoubtedly, precise identification of genetic abnormalities may lead to a better classification which may help to assign patients into sub-subgroups within the specific chromosomal abnormalities to initiate better therapeutic modalities and decisions.
Chromosome Deletion↗
Serendipity of Philadelphia chromosome.
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Humans↗