scholarly journals LD-CNV: rapid and simple discovery of chromosomal translocations using linkage disequilibrium between copy number variable loci

Genetics ◽  
2021 ◽  
Author(s):  
Luca Comai ◽  
Kirk Amundson ◽  
Benny Ordonez ◽  
Xin Zhao ◽  
Guilherme Tomaz Braz ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Copy Number ◽  
Fluorescent In Situ Hybridization ◽  
Large Scale ◽  
Chromosomal Translocations ◽  
Chromosome 1 ◽  
Structural Variations ◽  
Painting Probes ◽  
Two Populations

Abstract Large scale structural variations, such as chromosomal translocations, can have profound effects on fitness and phenotype, but are difficult to identify and characterize. Here, we describe a simple and effective method aimed at identifying translocations using only the dosage of sequence reads mapped on the reference genome. We binned reads on genomic segments sized according to sequencing coverage and identified instances when copy number segregated in populations. For each dosage-polymorphic 1Mb bin, we tested independence, effectively an apparent linkage disequilibrium (LD), with other variable bins. In nine potato (Solanum tuberosum) dihaploid families translocations affecting pericentromeric regions were common and in two cases were due to genomic misassembly. In two populations, we found evidence for translocation affecting euchromatic arms. In cv. PI 310467, a non-reciprocal translocation between chromosome 7 and 8 resulted in a 5-3 copy number change affecting several Mb at the respective chromosome tips. In cv. “Alca Tarma”, the terminal arm of chromosome 4 translocated to the tip of chromosome 1. Using oligonucleotide-based fluorescent in situ hybridization painting probes (oligo-FISH), we tested and confirmed the predicted arrangement in PI 310467. In 192 natural accessions of Arabidopsis thaliana, dosage haplotypes tended to vary continuously and resulted in higher noise, while apparent LD between pericentromeric regions suggested the effect of repeats. This method, LD-CNV, should be useful in species where translocations are suspected because it tests linkage without the need for genotyping.

scholarly journals LD-CNV: rapid and simple discovery of chromosomal translocations using linkage disequilibrium between copy number variable loci

2021 ◽  
Author(s):  
Luca Comai ◽  
Kirk R Amundson ◽  
Benny Ordonez ◽  
Xin Zhao ◽  
Guilherme Tomaz Braz ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Copy Number ◽  
Fluorescent In Situ Hybridization ◽  
Large Scale ◽  
Chromosomal Translocations ◽  
Chromosome 1 ◽  
Structural Variations ◽  
Painting Probes ◽  
Two Populations

Large scale structural variations, such as chromosomal translocations, can have profound effects on fitness and phenotype, but are difficult to identify and characterize. Here, we describe a simple and effective method aimed at identifying translocations using only the dosage of sequence reads mapped on the reference genome. We binned reads on genomic segments sized according to sequencing coverage and identified instances when copy number segregated in populations. For each dosage-polymorphic 1Mb bin, we tested linkage disequilibrium with other variable bins. In nine potato (Solanum tuberosum) dihaploid families translocations affecting pericentromeric regions were common and in two cases were due to genomic misassembly. In two populations, we found evidence for translocation affecting euchromatic arms. In cv. PI 310467, a non-reciprocal translocation between chromosome 7 and 8 resulted in a 5-3 copy number change affecting several Mb at the respective chromosome tips. In cv. Alca Tarma the terminal arm of chromosome 4 translocated to the tip of chromosome 1. Using oligonucleotide-based fluorescent in situ hybridization painting probes (oligo-FISH), we tested and confirmed the predicted arrangement in PI 310467. In 192 natural accessions of Arabidopsis thaliana, dosage haplotypes tended to vary continuously and resulted in higher noise, but we identified pericentromeric LD suggesting the effect of repeats. This method should be useful in species where translocations are suspected because it tests linkage without the need for genotyping.

scholarly journals Associations between Amplification (1q) and Prior Cancer in a Real-World De Novo Myeloma Cohort

2021 ◽  
Author(s):  
Elizabeth B Lamont ◽  
Andrew J Yee ◽  
Stuart L Goldberg ◽  
David S Siegel ◽  
Andrew D Norden
Keyword(s):  
Real World ◽  
Fluorescent In Situ Hybridization ◽  
De Novo ◽  
Chromosome 1 ◽  
Second Malignancies ◽  
Cancer History ◽  
Screening Strategies ◽  
Cytogenetic Testing

Abstract Genomic biomarkers inform treatment in multiple myeloma (MM) making patient clinical data a potential window into MM biology. We evaluated de novo MM patients for associations between specific MM cytogenetic patterns and prior cancer history. Analyzing a MM real-world dataset (RWD), we identified a cohort of 1,769 patients with fluorescent in-situ hybridization (FISH) cytogenetic testing at diagnosis. Fully 241 patients (0.14) had histories of prior cancer(s). Amplification of the long arm of chromosome 1 [amp(1q)] varied by prior cancer history (0.31 with prior cancer vs 0.24 without; p = .02). No other MM translocations, amplifications, or deletions were associated with prior cancers. Amp(1q) and cancer history remained strongly associated in a logistic regression adjusting for patient demographic and disease attributes. The results merit follow-up regarding carcinogenic treatment effects and screening strategies for second malignancies. Broadly the findings suggest analyses of patient-level phenotypic-genomic RWD may accelerate cancer research through hypothesis generating studies.

Recovery of a telomere-truncated chromosome via a compensating translocation in maize

Genome ◽  
2011 ◽  
Vol 54 (3) ◽  
pp. 184-195 ◽  
Author(s):  
Robert T. Gaeta ◽  
Tatiana V. Danilova ◽  
Changzeng Zhao ◽  
Rick E. Masonbrink ◽  
Morgan E. McCaw ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Fluorescent In Situ Hybridization ◽  
Transgene Expression ◽  
De Novo ◽  
Extra Chromosome ◽  
Single Gene ◽  
B Chromosomes ◽  
Chromosome 1 ◽  
Chromosome 6

Maize-engineered minichromosomes are easily recovered from telomere-truncated B chromosomes but are rarely recovered from A chromosomes. B chromosomes lack known genes, and their truncation products are tolerated and transmitted during meiosis. In contrast, deficiency gametes resulting from truncated A chromosomes prevent their transmission. We report here a de novo compensating translocation that permitted recovery of a large truncation of chromosome 1 in maize. The truncation (trunc-1) and translocation with chromosome 6 (super-6) occurred during telomere-mediated truncation experiments and were characterized using single-gene fluorescent in situ hybridization (FISH) probes. The truncation contained a transgene signal near the end of the broken chromosome and transmitted together with the compensating translocation as a heterozygote to approximately 41%–55% of progeny. Transmission as an addition chromosome occurred in ~15% of progeny. Neither chromosome transmitted through pollen. Transgene expression (Bar) cosegregated with trunc-1 transcriptionally and phenotypically. Meiosis in T1 plants revealed eight bivalents and one tetravalent chain composed of chromosome 1, trunc-1, chromosome 6, and super-6 in diplotene and diakinesis. Our data suggest that de novo compensating translocations allow recovery of truncated A chromosomes by compensating deficiency in female gametes and by affecting chromosome pairing and segregation. The truncated chromosome can be maintained as an extra chromosome or together with the super-6 as a heterozygote.

Fluorescent in situ hybridization assessment of chromosomes 1 and 17 copy number in neoplastic and normal tissues of cancer-associated breasts

The Breast ◽  
1997 ◽  
Vol 6 (5) ◽  
pp. 324-325
Author(s):  
C. Botti ◽  
R. Bovani ◽  
C. Greco ◽  
F. Cavaliere ◽  
M. Benevolo ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Copy Number ◽  
Fluorescent In Situ Hybridization ◽  
Normal Tissues

scholarly journals The distribution of transposable elements within and between chromosomes in a population of Drosophila melanogaster. I. Element frequencies and distribution

1992 ◽  
Vol 60 (2) ◽  
pp. 103-114 ◽  
Author(s):  
Brian Charlesworth ◽  
Angela Lapid ◽  
Darlene Canada
Keyword(s):  
Population Dynamics ◽  
Drosophila Melanogaster ◽  
Linkage Disequilibrium ◽  
Transposable Elements ◽  
Copy Number ◽  
Polytene Chromosomes ◽  
Chromosome Band ◽  
High Frequencies ◽  
Copy Numbers

SummaryData were collected on the distribution of nine families of transposable elements among second and third chromosomes isolated from a natural population of Drosophila melanogaster, by means of in situ hybridization of element probes to polytene chromosomes. It was found that the copy numbers per chromosome in the distal sections of the chromosome arms followed a Poisson distribution. Elements appeared to be distributed randomly along the distal sections of the chromosome arms. There was no evidence for linkage disequilibrium in the distal sections of the chromosomes, but some significant disequilibrium was detected in proximal regions. There were many significant correlations between different element families with respect to the identity of the sites that were occupied in the sample. There were also significant correlations between families with respect to sites at which elements achieved relatively high frequencies. Element frequencies per chromosome band were generally low in the distal sections, but were higher proximally. These results are discussed in the light of models of the population dynamics of transposable elements. It is concluded that they provide strong evidence for the operation of a force or forces opposing transpositional increase in copy number. The data suggest that the rate of transposition perelement per generation is of the order of 10−4, for the elements included in this study.

Low‐depth sequencing for copy number abnormalities in multiple myeloma supersedes fluorescent in situ hybridization in scope and resolution

2019 ◽  
Vol 96 (2) ◽  
pp. 163-168 ◽  
Author(s):  
Manal O. Elnenaei ◽  
Philipp Knopf ◽  
Samuel D. Cutler ◽  
Keaton Sinclair ◽  
Mohamed Abou El Hassan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
In Situ Hybridization ◽  
Copy Number ◽  
Fluorescent In Situ Hybridization

Assessment of Chromosome 8 Copy Number in Cervical Cancer by Fluorescent in situ Hybridization

1999 ◽  
Vol 66 (2) ◽  
pp. 157-162 ◽  
Author(s):  
H.F.L. Mark ◽  
D. Feldman ◽  
M. Samy ◽  
C.-L. Sun ◽  
Sam Das ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
In Situ Hybridization ◽  
Copy Number ◽  
Fluorescent In Situ Hybridization ◽  
Chromosome 8

Mosaicism due to myeloid lineage–restricted loss of heterozygosity as cause of spontaneous Rh phenotype splitting

Blood ◽  
2007 ◽  
Vol 110 (6) ◽  
pp. 2148-2157 ◽  
Author(s):  
Günther F. Körmöczi ◽  
Eva-Maria Dauber ◽  
Oskar A. Haas ◽  
Tobias J. Legler ◽  
Frederik B. Clausen ◽  
...  
Keyword(s):  
Blood Group ◽  
Loss Of Heterozygosity ◽  
Fluorescent In Situ Hybridization ◽  
Microsatellite Analysis ◽  
Red Cells ◽  
Chromosome 1 ◽  
Hematologic Disease ◽  
Myeloid Lineage ◽  
Hematopoietic Stem

Abstract Spontaneous Rh phenotype alteration interferes with pretransfusion and prenatal blood group examinations and may potentially indicate hematologic disease. In this study, the molecular background of this biologic phenomenon was investigated. In 9 patients (3 with hematologic disease), routine RhD typing showed a mixture of D-positive and D-negative red cells not attributable to transfusion or hematopoietic stem-cell transplantation. In all patients, congenital and acquired chimerism was excluded by microsatellite analysis. In contrast to D-positive red cells, D-negative subpopulations were also negative for C or E in patients genotyped CcDdee or ccDdEe, respectively, which suggested the presence of erythrocyte precursors with an apparent homozygous cde/cde or hemizygous cde/— genotype. Except for one patient with additional Fyb antigen anomaly, no other blood group systems were affected. RH genotyping of single erythropoietic burst-forming units, combined with microsatellite analysis of blood, different tissues, sorted blood cell subsets, and erythropoietic burst-forming units, indicated myeloid lineage–restricted loss of heterozygosity (LOH) of variable chromosome 1 stretches encompassing the RHD/RHCE gene loci. Fluorescent in situ hybridization studies indicated that LOH was caused by either somatic recombination or deletion. Therefore, most cases of spontaneous Rh phenotype splitting appear to be due to hematopoietic mosaicism based on LOH on chromosome 1.

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