Origin Of Chromosomal Aberrations Research Articles

Phenotypic and genetic analysis of a child with partial trisomy 7q

To define the nature and origin of a chromosomal aberration in a child with unexplained growth and development retardation, and to analyze its genotype-phenotype correlation. A child who had presented at the Affiliated Children's Hospital of Zhengzhou University on July 9, 2019 was selected as the study subject. Chromosomal karyotypes of the child and her parents were determined with routine G-banding analysis. Their genomic DNA was also analyzed with single nucleotide polymorphism array (SNP array). Karyotyping analysis combined with SNP array suggested that the chromosomal karyotype of the child was 46,XX,dup(7)(q34q36.3), whilst no karyotypic abnormality was found in either of her parents. SNP array has identified a de novo 20.6 Mb duplication at 7q34q36.3 [arr[hg19] 7q34q36.3(138335828_158923941)×3] in the child. The partial trisomy 7q carried by the child was rated as a de novo pathogenic variant. SNP array can clarify the nature and origin of chromosomal aberrations. Analysis of the correlation between genotype and phenotype can facilitate the clinical diagnosis and genetic counseling.

Detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation

Subtelomeric regions of chromosomes are rich in genes; their rearrangements cannot be identified by traditional chromosome analysis. Since these subtelomeric aberrations are responsible for about 7% of cases with mental retardation, their detection is important both from the diagnostic point of view and to prevent recurrence in the family. Subtelomeric chromosomal alterations can be detected by fluorescence in situ hybridization. Based on international criteria, 35 out of 59 patients with mental retardation have been selected. Subtelomeric rearrangements were revealed in 6 patients (5 familial cases, 1 new onset) whereas the subtelomeric FISH result was normal in 29 cases. Deletion of 8pter and duplication of 12pter were detected in 2 patients, while a deletion of 21qter and duplication of the 10pter due to an unbalanced translocation were found in 3 other cases. Finally, a new onset deletion of 3qter was observed in 1 patient. In order to clarify the origin of chromosome aberrations, 12 healthy family members were also examined, 5 of them carried balanced translocations. We concluded that the phenotype is mostly influenced by the size of regions involved in deletion/duplication and - in case of translocations - by the associated chromosomal abnormalities.

Reverse painting highlights the origin of chromosome aberrations.

Reverse chromosome painting, as the opposite of forward chromosome painting, means that an abnormal chromosome of interest is recovered by flow sorting or by chromosome microdissection, amplified and labelled by DOP-PCR and hybridized onto normal metaphases of optimal quality. This provides rapid and unequivocal information about the chromosomal origin on the aberrant chromosome in one hybridization. Not only will the specific chromosome(s) involved be identified, but also the subchromosomal origin, including the breakpoints. The method has been used for over 10 years and has proven to be very useful for resolving complex chromosome rearrangements in a variety of different applications, both as a research tool and for clinical purposes in pre- and postnatal diagnosis.

Analysis of structural and numerical chromosome abnormalities in sperm of normal men and carriers of constitutional chromosome aberrations. A review.

Sperm chromosome analysis offers the opportunity to gather information about the origin of chromosome aberrations in human germ cells. Over the last 20 years more than 20,000 sperm chromosome complements from normal donors and almost 6000 spermatozoa from men with constitutional chromosome aberrations (inversions, translocations) have been analyzed for structural and numerical chromosome abnormalities, as well as for segregation of the constitutional chromosome aberrations after the sperm had penetrated hamster oocytes. On the other hand, it took only 6 years to screen more than 3 million mature spermatozoa from healthy probands for disomy rates of 20 autosomes (chromosomes 19 and 22 not evaluated) and the sex chromosomes, and for diploidy rates by in situ hybridization techniques. In the present paper the results arising from both methods are compiled and compared.

Chromosomenaberrationen bei akuten Leukämien im Kindesalter: Analyse von1009 Patienten1, 2

Leukemia karyotypes were analyzed in 792 children with acute lymphoblastic leukemia (ALL) and 217 patients with acute myelocytic leukemia (AML). These patients were registered and uniformly treated in German multicentre trials from 1984-01-01 to 1989-12-31. In distinct leukemia subgroups specific chromosome abnormalities were found: Numerical aberrations such as hyperdiploidy over 50 chromosomes in c-ALL or structural aberrations (translocations) such as t(8;14) in B-ALL, t(11;14) in T-ALL, t(4;11) in ppB-ALL, t(1;19) in pB-ALL, t(15;17) in AML-M3, t(8;21) in AML-M2. Prognostic significance of the leukemia karyotype probably can be changed by intensive cytotoxic chemotherapy. Unfavorable prognosis, however, still persists in t(9;22) and t(4;11); "favorable" prognosis can be seen in t(8;21) and t(15;17). Inherited or induced chromosome instability is discussed as a possible predisposing factor for the origin of chromosome aberrations.

Origin of chromosomal aberrations by DNA double-strand breaks

Origin of chromosomal aberrations by DNA double-strand breaks

Silver Staining in Clinical Cytogenetics

Silver staining of human chromosomes at prometaphase or metaphase identifies variants in the stalk (nucleolar organizing) regions of acrocentric chromosomes (Nos. 13, 14, 15, 21, 22). Variants are defined by size, number, and morphology of silver staining areas. They are heritable polymorphisms and have not been associated with clinical abnormalities. However, these variants are useful in clinical cytogenetics, specifically in studies attempting to determine whether genetic material has been gained or lost in chromosomal rearrangements, the origin of chromosomal aberrations, the origin of cells in tissue culture, the chromosomal location of single genes, clonal origin of tumors, the zygosity of twins, and paternity. Some chromosomal aberrations require silver staining for their definition. Because loss of the stalk regions per se is apparently not deleterious, demonstration that chromosomal breaks occurred within this region without concomitant loss or gain of genetic material essential for normal human development provides basis for a good prognosis for the individual with the chromosomal rearrangement resulting from such breakage. The principle underlying most of the other applications is to determine whether variants being compared are identical or dissimilar, and to make inferences from these results (e.g., variants in monozygotic twins should all be identical, whereas in dizygotic twins they are as similar as in any pair of sibs). Silver staining is a valuable technique for special questions in clinical analysis.

On the origin of chromosomal aberrations in human peripheral lymphocytes in vitro. I. Experiments with Neurospora endonuclease and polyethylene glycol.

Post-treatment of mutagen-treated human peripheral lymphocytes with a single-strand specific endonuclease from Neurospora crassa leads to a significant elevation of the rate of structural chromosomal aberrations. Our results indicate that DNA double-strand breaks (DSB) are ultimate lesions for the formation of chromosomal aberrations in the G1 and G2 phase of the cell cycle and probably also in the S-phase. Post-treatment of X-irradiated G2 cells with polyethylene glycol (PEG) leads to an elevation of the frequencies of chromatid type aberrations. This result is taken as an indication that nucleases from PEG-damaged lysosomes transform lesions in X-ray damaged chromosomes to DSB. With respect to the origin of chromosomal aberrations, our results are in favour of the breakage and reunion hypothesis of K. Sax , and not of Revell 's exchange hypothesis.

On the origin of chromosomal aberrations

On the origin of chromosomal aberrations

Analysis of intercellular distributions of chromatid aberrations

59 intercellular distributions of chemically induced and spontaneous chromatid aberrations were analyzed for goodness of fit in respect of the Poisson (PD), the geometrical (GD), and the negative binomial distributions (NBD). The data are excellently described by the NBD. This distribution can be deduced from a model out of the queueing theory and is based on the hypothesis of restitution. Estimators are obtained for the ratio of restitution and induction processes involved in the origin of chromosomal aberrations.