scholarly journals Inherited unbalanced reciprocal translocation with 3q duplication and 5p deletion in a foetus revealed by cell-free foetal DNA (cffDNA) testing: a case report

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Taccyanna M. Ali ◽  
Emilia Mateu-Brull ◽  
Nuria Balaguer ◽  
Camila Dantas ◽  
Haline Risso Borges ◽  
...  
Keyword(s):  
Reciprocal Translocation ◽  
Chromosomal Rearrangements ◽  
Structural Rearrangement ◽  
Maternal Blood ◽  
Copy Number Variations ◽  
Clinical Tool ◽  
Chromosome 5 ◽  
Case Presentation ◽  
5P Deletion ◽  
Multiple Abnormalities

Abstract Background Since 2011, screening maternal blood for cell-free foetal DNA (cffDNA) fragments has offered a robust clinical tool to classify pregnancy as low or high-risk for Down, Edwards, and Patau syndromes. With recent advances in molecular biology and improvements in data analysis algorithms, the screening’s scope of analysis continues to expand. Indeed, screening now encompassess additional conditions, including aneuploidies for sex chromosomes, microdeletions and microduplications, rare autosomal trisomies, and, more recently, segmental deletions and duplications called copy number variations (CNVs). Yet, the ability to detect CNVs creates a new challenge for cffDNA analysis in couples in which one member carries a structural rearrangement such as a translocation or inversion. Case presentation We report a segmental duplication of the long arm of chromosome 3 and a segmental deletion of the short arm of chromosome 5 detected by cffDNA analysis in a 25-year-old pregnant woman. The blood sample was sequenced on a NextSeq 550 (Illumina) using the VeriSeq NIPT Solution v1 assay. G-band karyotyping in amniotic fluid only detected an abnormality in chromosome 5. Next-generation sequencing in amniocytes confirmed both abnormalities and identified breakpoints in 3q26.32q29 and 5p13.3p15. The foetus died at 21 weeks of gestation due to multiple abnormalities, and later G-band karyotyping in the parents revealed that the father was a carrier of a balanced reciprocal translocation [46,XY,t(3;5)(q26.2;p13)]. Maternal karyotype appeared normal. Conclusion This case provides evidence that extended cffDNA can detect, in addition to aneuploidies for whole chromosomes, large segmental aneuploidies. In some cases, this may indicate the presence of chromosomal rearrangements in a parent. Such abnormalities are outside the scope of standard cffDNA analysis targeting chromosomes 13, 18, 21, X, and Y, potentially leading to undiagnosed congenital conditions.

Inherited unbalanced reciprocal translocation with 3q duplication and 5p deletion in a foetus revealed by Cell-Free foetal DNA (cffDNA) testing: A case report

2021 ◽  
Author(s):  
Taccyanna Mikulski Ali ◽  
Emilia Mateu-Brull ◽  
Nuria Balaguer ◽  
Camila Dantas de Souza ◽  
Haline Risso Borges ◽  
...  
Keyword(s):  
Reciprocal Translocation ◽  
Chromosomal Rearrangements ◽  
Structural Rearrangement ◽  
Maternal Blood ◽  
Copy Number Variations ◽  
Clinical Tool ◽  
Chromosome 5 ◽  
5P Deletion ◽  
Multiple Abnormalities ◽  
Generation Sequencing

Abstract BackgroundSince 2011, screening maternal blood for cell-free foetal DNA (cffDNA) fragments has offered a robust clinical tool to classify pregnancy as low or high-risk for Down, Edwards, and Patau syndromes. With recent advances in molecular biology and improvements in data analysis algorithms, the screening’s scope of analysis continues to expand. Indeed, screening now encompassess additional conditions, including aneuploidies for sex chromosomes, microdeletions and microduplications, rare autosomal trisomies, and, more recently, segmental deletions and duplications called copy number variations (CNVs). Yet, the ability to detect CNVs creates a new challenge for cffDNA analysis in couples in which one member carries a structural rearrangement such as a translocation or inversion.Case presentationWe report a segmental duplication of the long arm of chromosome 3 and a segmental deletion of the short arm of chromosome 5 detected by cffDNA analysis in a 25-year-old pregnant woman. G-band karyotyping in amniotic fluid only detected an abnormality in chromosome 5. Next-generation sequencing in amniocytes confirmed both abnormalities and identified breakpoints in 3q26.32q29 and 5p13.3p15. The foetus died at 21 weeks of gestation due to multiple abnormalities, and later G-band karyotyping in the parents revealed that the father was a carrier of a balanced reciprocal translocation [46,XY,t(3;5)(q26.2;p13)]. Maternal karyotype appeared normal.ConclusionThis case provides evidence that extended cffDNA can detect, in addition to aneuploidies for whole chromosomes, large segmental aneuploidies. In some cases, this may indicate the presence of chromosomal rearrangements in a parent. Such abnormalities are outside the scope of standard cffDNA analysis targeting chromosomes 13, 18, 21, X, and Y, potentially leading to undiagnosed congenital conditions.

scholarly journals dbVar structural variant cluster set for data analysis and variant comparison

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 673 ◽  
Author(s):  
Lon Phan ◽  
Jeffrey Hsu ◽  
Le Quang Minh Tri ◽  
Michaela Willi ◽  
Tamer Mansour ◽  
...  
Keyword(s):  
Genomic Sequence ◽  
Chromosomal Rearrangements ◽  
Copy Number Variations ◽  
Structural Variant ◽  
Variant Type ◽  
External Data ◽  
Cluster Set ◽  
Genomic Location ◽  
Complex Chromosomal Rearrangements ◽  
Genomic Regions

dbVar houses over 3 million submitted structural variants (SSV) from 120 human studies including copy number variations (CNV), insertions, deletions, inversions, translocations, and complex chromosomal rearrangements. Users can submit multiple SSVs to dbVAR  that are presumably identical, but were ascertained by different platforms and samples,  to calculate whether the variant is rare or common in the population and allow for cross validation. However, because SSV genomic location reporting can vary – including fuzzy locations where the start and/or end points are not precisely known – analysis, comparison, annotation, and reporting of SSVs across studies can be difficult. This project was initiated by the Structural Variant Comparison Group for the purpose of generating a non-redundant set of genomic regions defined by counts of concordance for all human SSVs placed on RefSeq assembly GRCh38 (RefSeq accession GCF_000001405.26). We intend that the availability of these regions, called structural variant clusters (SVCs), will facilitate the analysis, annotation, and exchange of SV data and allow for simplified display in genomic sequence viewers for improved variant interpretation. Sets of SVCs were generated by variant type for each of the 120 studies as well as for a combined set across all studies. Starting from 3.64 million SSVs, 2.5 million and 3.4 million non-redundant SVCs with count >=1 were generated by variant type for each study and across all studies, respectively. In addition, we have developed utilities for annotating, searching, and filtering SVC data in GVF format for computing summary statistics, exporting data for genomic viewers, and annotating the SVC using external data sources.

scholarly journals Allelic loss of IRF1 in myelodysplasia and acute myeloid leukemia: retention of IRF1 on the 5q- chromosome in some patients with the 5q- syndrome

Blood ◽  
1993 ◽  
Vol 82 (9) ◽  
pp. 2611-2616 ◽  
Author(s):  
J Boultwood ◽  
C Fidler ◽  
S Lewis ◽  
A MacCarthy ◽  
H Sheridan ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Gene Dosage ◽  
Structural Rearrangement ◽  
Suppressor Gene ◽  
Allelic Loss ◽  
Chromosome 5 ◽  
Putative Tumor Suppressor Gene ◽  
5Q Deletion ◽  
Acute Myeloid

Abstract Acquired interstitial deletions of the long arm of chromosome 5 occur frequently in the myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Recently IRF1, a putative tumor suppressor gene localized to the long arm of chromosome 5, has been shown to be deleted from the 5q- chromosome in a group of patients with MDS and AML. It has been suggested that the loss of IRF1 may be critical to the development of the 5q- syndrome. We have investigated the allelic loss of IRF1 in a group of 12 patients with MDS and a 5q deletion and 2 patients with AML and a 5q deletion. Gene dosage experiments demonstrated that 12 of 14 patients had loss of one allele of the IRF1 gene but no evidence of homozygous loss and that 2 patients with 5q- syndrome retained both copies of the gene. The retention of IRF1 on the 5q- chromosome in these two cases has been confirmed by fluorescent in situ hybridization localization using an IRF1 cosmid. Pulsed field gel electrophoresis was used to determine whether there was any evidence for structural rearrangement in the region encompassing the IRF1 gene in these two patients. No aberrant bands were detected with a range of rare cutter enzyme digests. We conclude that IRF1 maps outside the commonly deleted segment of the 5q- chromosome and that loss of IRF1 is not solely responsible for the development of the 5q- syndrome.

Chromosomal rearrangements in rock wallabies, Petrogale (Marsupialia: Macropodidae). III. G-banding analysis of Petrogale inornata and P. penicillata

Genome ◽  
1990 ◽  
Vol 33 (6) ◽  
pp. 798-802 ◽  
Author(s):  
M. D. B. Eldridge ◽  
R. L. Close ◽  
P. G. Johnston
Keyword(s):  
Acrocentric Chromosome ◽  
Chromosomal Rearrangements ◽  
Paracentric Inversion ◽  
Chromosome 3 ◽  
Chromosome 4 ◽  
Chromosome 5 ◽  
Cultured Fibroblasts ◽  
Submetacentric Chromosome ◽  
Ancestral Chromosome ◽  
Banding Analysis

The karyotypes of Petrogale inornata and the two currently recognised races of Petrogale penicillata were examined using G-banding from cultured fibroblasts. Petrogale inornata (2n = 22) was found to retain plesiomorphic chromosomes 3 and 4 but possessed an apomorphic inverted chromosome 5 (5i). This 5i appears identical with the 5i found in two other Queensland taxa, Petrogale assimilis and Petrogale godmani, and can be derived from the ancestral chromosome 5 by an extensive paracentric inversion or a centromeric transposition. Petrogale penicillata penicillata (2n = 22) and Petrogale penicillata herberti (2n = 22) both possess the synapomorphic acrocentric chromosome 3, which appears to differ from the plesiomorphic 3 by a small centromeric transposition. Petrogale p. penicillata was also found to be characterised by an apomorphic acrocentric chromosome 4, while P. p. herberti was characterised by an autapomorphic submetacentric chromosome 4. Both apomorphic chromosomes 4 can be related to the plesiomorphic chromosome 4 by centromeric transpositions. Thus although P. inornata is chromosomally distinct it is more closely related to other north Queensland taxa than it is to either P. p. penicillata or P. p. herberti.Key words: chromosomal rearrangements, G-banding, Marsupialia, Petrogale, Macropodidae.

scholarly journals A case of germline mosaicism for a 7q32.1q33 deletion in a sperm donor: consequences on pregnancy follow-up and recommendations

2020 ◽  
Vol 30 (1) ◽  
Author(s):  
Celine Chalas ◽  
Aline Receveur ◽  
Nelly Frydman ◽  
Nathalie Massin ◽  
Gerard Tachdjian ◽  
...  
Keyword(s):  
Chromosomal Rearrangements ◽  
Rare Event ◽  
Copy Number Variations ◽  
Paternal Age ◽  
Comparative Genomic ◽  
Fish Analysis ◽  
Sperm Donor ◽  
Germline Mosaicism ◽  
Talipes Equinovarus

Abstract Background Germline mosaicism is considered to be a rare event. However, its occurrence is underestimated due to the limited availability of germ cells. The genomic variations that underlie this phenomenon comprise single nucleotide polymorphism (SNPs), copy number variations (CNVs) and aneuploidies. In the case of CNVs, deletions are more frequent in the paternal germline while duplications are more commonly maternal in origin. Germline mosaicism increases with paternal age as the risk of SNPs increase with the number of germ cell divisions. We here report a case of germline mosaicism in the spermatozoa of a donor that resulted in one pathological pregnancy. Results Straws from the same sperm donor were provided to seven recipient couples, resulting in four pregnancies. Second trimester ultrasound analysis revealed bilateral talipes equinovarus associated with growth retardation in one of these pregnancies. Array-comparative genomic hybridization (CGH) carried out after amniocentesis revealed a 4 Mb deletion in the 7q32.1q33 region. The blood karyotypes and array-CGHs were normal in the mother, as well as in the donor. However, the microsatellite profile indicated a paternal origin. Fluorescent in situ hybridization (FISH) analysis of the donor’s spermatozoa revealed the same chromosomal rearrangements in 12% of the spermatozoa population. Due to the documented risk of mental retardation associated with genomic rearrangements in the same region, the couple decided to terminate the pregnancy. Amniocentesis was performed in the other couples, which yielded normal FISH analysis results. Conclusions Several cases of germline mosaicism have been reported to date, but their frequency is probably underestimated. Moreover, it is important to note that germline mosaicism cannot be ruled out by conventional cytogenetic screening of blood cells. This case highlights the need for close follow-up of every pregnancy obtained through gamete donation, given that the occurrence of germline mosaicism may have major consequences when multiple pregnancies are obtained concomitantly.

scholarly journals Deletions extending from a single Ty1 element in Saccharomyces cerevisiae.

1985 ◽  
Vol 5 (12) ◽  
pp. 3451-3457 ◽  
Author(s):  
K M Downs ◽  
G Brennan ◽  
S W Liebman
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cytochrome C ◽  
Reciprocal Translocation ◽  
Restriction Site ◽  
Chromosomal Rearrangements ◽  
Yeast Cells ◽  
Site Specific ◽  
Site Specific Recombination ◽  
The Third ◽  
Deletion Junction

Chromosomal rearrangements associated with one Ty1 element in the iso-1-cytochrome c (CYC1) region of Saccharomyces cerevisiae yeast cells were examined. Most of the rearrangements were deletions of the three linked genes, CYC1, OSM1, and RAD7, and resulted from recombination involving the single Ty1 element and a solo delta in the same orientation. These deletions differed by the number of Ty1 elements (zero, one, or two) remaining after deletion and by restriction site heterogeneities associated with these elements. A single Ty1 element remained at the deletion junction point much more frequently than no Ty1. Apparently the Ty1-associated delta element nearer to the solo delta was involved more often in recombination than the more distal Ty1-associated delta element. The restriction site data implicate gene conversion and suggest that site-specific recombination within the deltas, if occurring, is not the only mechanism of delta-delta recombination. Three other rearrangements bore deletions which began at the end of the Ty1 element and extended into regions not bearing Ty1 or delta sequences. Two of these deletions eliminated 7 kilobases of DNA, although they differed by an associated reciprocal translocation. The third involved a deletion of 14.7 kilobases of DNA associated with an overlapping inversion.

scholarly journals Karyotype variations in Italian populations of the peach-potato aphid Myzus persicae (Hemiptera: Aphididae)

2012 ◽  
Vol 102 (6) ◽  
pp. 663-671 ◽  
Author(s):  
M. Rivi ◽  
V. Monti ◽  
E. Mazzoni ◽  
S. Cassanelli ◽  
M. Panini ◽  
...  
Keyword(s):  
Chromosomal Aberrations ◽  
Myzus Persicae ◽  
Reciprocal Translocation ◽  
Chromosomal Rearrangements ◽  
Chromosomal Mosaicism ◽  
Tobacco Plants ◽  
Potato Aphid ◽  
Cytogenetic Data ◽  
Clastogenic Effect ◽  
Peach Potato Aphid

AbstractIn this study, we present cytogenetic data regarding 66 Myzus persicae strains collected in different regions of Italy. Together with the most common 2n = 12 karyotype, the results showed different chromosomal rearrangements: 2n = 12 with A1–3 reciprocal translocation, 2n = 13 with A1–3 reciprocal translocation and A3 fission, 2n = 13 with A3 fission, 2n = 13 with A4 fission, 2n = 14 with X and A3 fissions. A 2n = 12–13 chromosomal mosaicism has also been observed. Chromosomal aberrations (and in particular all strains showing A1–3 reciprocal translocation) are especially frequent in strains collected on tobacco plants, and we suggest that a clastogenic effect of nicotine, further benefited by the holocentric nature of aphid chromosomes, could be at the basis of the observed phenomenon.

Chromosomal rearrangements in rock wallabies, Petrogale (Marsupialia: Macropodidae). II. G-banding analysis of Petrogale godmani

Genome ◽  
1989 ◽  
Vol 32 (6) ◽  
pp. 935-940 ◽  
Author(s):  
M. D. B. Eldridge ◽  
P. G. Johnston ◽  
R. L. Close ◽  
P. S. Lowry
Keyword(s):  
Chromosomal Rearrangements ◽  
Centric Fusion ◽  
Common Ancestry ◽  
Chromosome 4 ◽  
Chromosome 5 ◽  
Separate Species ◽  
Submetacentric Chromosome ◽  
Ancestral Chromosome ◽  
Banding Analysis ◽  
Cape York

Chromosomal rearrangements in the two currently recognised races of Petrogale godmani were examined using C- and G-banding. The nominate race P. godmani godmani (2n = 20) was found to possess an inverted chromosome 5 and an acrocentric 6–10 fusion, which can be derived from a 6–10 centric fusion by a centromeric transposition. The Cape York race (2n = 22) was found to retain the ancestral submetacentric chromosome 4 and the ancestral chromosome 5. Thus despite their genie similarity, the two races clearly have major chromosomal differences and should be regarded as separate species. Petrogale g. godmani shares two derived chromosomes with another Queensland taxon, the assimilis race of P. assimilis, indicating recent common ancestry. The Cape York race retains characteristics of an ancestral stock of Petrogale and its genic similarity with P. g. godmani could therefore be the result of extensive introgression.Key words: chromosomal rearrangements, G-banding, Marsupialia, Petrogale.

scholarly journals Chromosomal rearrangements are commonly post-transcriptionally attenuated in cancer

2016 ◽  
Author(s):  
Emanuel Gonçalves ◽  
Athanassios Fragoulis ◽  
Luz Garcia-Alonso ◽  
Thorsten Cramer ◽  
Julio Saez-Rodriguez ◽  
...  
Keyword(s):  
Copy Number ◽  
Protein Complexes ◽  
Chromosomal Rearrangements ◽  
Proteasome Inhibitors ◽  
Gene Signature ◽  
Copy Number Variations ◽  
Data Sets ◽  
Regulatory Interactions ◽  
The Impact ◽  
Rate Limiting

AbstractChromosomal rearrangements, despite being detrimental, are ubiquitous in cancer and often act as driver events. The effect of copy number variations (CNVs) on the cellular proteome of tumours is poorly understood. Therefore, we have analysed recently generated proteogenomic data-sets on 282 tumour samples to investigate the impact of CNVs in the proteome of these cells. We found that CNVs are post-transcriptionally attenuated in 23-33% of proteins with an enrichment for protein complexes. Complex subunits are highly co-regulated and some act as rate-limiting steps of complex assembly, indirectly controlling the abundance of other complex members. We identified 48 such regulatory interactions and experimentally validated AP3B1 and GTF2E2 as controlling subunits. Lastly, we found that a gene-signature of protein attenuation is associated with increased resistance to chaperone and proteasome inhibitors. This study highlights the importance of post-transcriptional mechanisms in cancer which allow cells to cope with their altered genomes.

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