Flanking complex copy number variants in the same family formed through unequal crossing-over during meiosis

Pettersson, Maria; Eisfeldt, Jesper; Lundberg, Elisabeth Syk; Lundin, Johanna; Wedell, Anna

doi:10.1016/j.mrfmmm.2018.10.001

Cited by 6 publications

(5 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, such events may also seed further instances of complex recombination or genomic instability, as shown in the evolution of a chromothriptic rearrangement in a mother into a chromoanasynthesis rearrangement in her daughter. 75 Functional Impact of Congenital Chromoanagenesis Chromoanagenesis events can impact genome function through multiple avenues, including deletion or truncation of disease-associated genes, triplication of clinically relevant genomic segments, generation of pathogenic gene fusions, or effects on gene expression through removal/ repositioning of important regulatory elements (Figure 3).…”

Section: Chromoanasynthesismentioning

confidence: 99%

The Iceberg under Water: Unexplored Complexity of Chromoanagenesis in Congenital Disorders

Zepeda-Mendoza

Morton

2019

The American Journal of Human Genetics

View full text Add to dashboard Cite

Structural variation, composed of balanced and unbalanced genomic rearrangements, is an important contributor to human genetic diversity with prominent roles in somatic and congenital disease. At the nucleotide level, structural variants (SVs) have been shown to frequently harbor additional breakpoints and copy-number imbalances, a complexity predicted to emerge wholly as a single-cell division event. Chromothripsis, chromoplexy, and chromoanasynthesis, collectively referred to as chromoanagenesis, are three major mechanisms that explain the occurrence of complex germline and somatic SVs. While chromothripsis and chromoplexy have been shown to be key signatures of cancer, chromoanagenesis has been detected in numerous cases of developmental disease and phenotypically normal individuals. Such observations advocate for a deeper study of the polymorphic and pathogenic properties of complex germline SVs, many of which go undetected by traditional clinical molecular and cytogenetic methods. This review focuses on congenital chromoanagenesis, mechanisms leading to occurrence of these complex rearrangements, and their impact on chromosome organization and genome function. We highlight future applications of routine screening of complex and balanced SVs in the clinic, as these represent a potential and often neglected genetic disease source, a true ''iceberg under water.''

show abstract

Section: Chromoanasynthesismentioning

confidence: 99%

The Iceberg under Water: Unexplored Complexity of Chromoanagenesis in Congenital Disorders

Zepeda-Mendoza

Morton

2019

The American Journal of Human Genetics

View full text Add to dashboard Cite

show abstract

“…It has been shown that copy number at Rhg1 is unstable within a released variety over a relatively small number of generations due to NAHR or UCO [47][48][49][50] . NAHR has also been shown to be responsible for CNV of different alleles at the I (inhibitor) locus in soybean for the colors of seed coat 77 , and many other CNV-based phenotypic variation [78][79][80] .…”

Section: Gynoecy Instability and Cnv Dynamics In Gynoecious Cucumbersmentioning

confidence: 99%

Gynoecy instability in cucumber (Cucumis sativus L.) is due to unequal crossover at the copy number variation-dependent Femaleness (F) locus

Han

Niu

et al. 2020

Hortic Res

View full text Add to dashboard Cite

Cucumber, Cucumis sativus is an important vegetable crop, and gynoecy has played a critical role in yield increase of hybrid cucumber production. Cucumber has a unique genetic system for gynoecious sex expression, which is determined by the copy number variation (CNV)-based, dominant, and dosage-dependent femaleness (F) locus. However, this gynoecy expression system seems unstable since monecious plants could often be found in Fdependent gynoecious cucumber inbreds. We hypothesized that gynoecy instability (gynoecy loss) may be due to unequal crossing over (UCO) during meiosis among repeat units of the CNV. In this study, using high throughput genome resequencing, fiber-FISH and genomic qPCR analyses, we first confirmed and refined the structure of the F locus, which was a CNV of a 30.2-kb tandem repeat. Gynoecious plants contained three genes: CsACS1, CsACS1G, and CsMYB, of which CsACS1G is a duplication of CsACS1 but with a recombinant distal promoter that may contribute to gynoecy sex expression. In two large populations from self-pollinated gynoecious inbred lines, 'gynoecy loss' mutants were identified with similar mutation rates (~0.12%). We show that these monecious mutants have lost CsACS1G. In addition, we identified gynoecious lines in natural populations that carry two copies of CSACS1G. We proposed a model to explain gynoecy instability in F-dependent cucumbers, which is caused by UCO among CSACS1/G units during meiosis. The findings present a convincing case that the phenotypic variation of an economically important trait is associated with the dynamic changes of copy numbers at the F locus. This work also has important implications in cucumber breeding.

show abstract

“…Clustered CNVs detected by chromosomal microarray analysis (CMA) are frequently reported as constitutional chromothripsis (47). Pettersson et al (48) presented two different rearrangements on chromosome 5p in a mother and her daughter, initially classified as simple CNVs. Using a combination of microarray analysis and massive parallel whole-genome sequencing, it was shown that, due to unequal crossing-over during meiosis, there was an evolution from a chromothriptic rearrangement in the mother to another complex rearrangement involving both deletions and duplications in her daughter (48).…”

Section: Cnvs and Constitutional Chromothripsismentioning

confidence: 99%

“…Pettersson et al (48) presented two different rearrangements on chromosome 5p in a mother and her daughter, initially classified as simple CNVs. Using a combination of microarray analysis and massive parallel whole-genome sequencing, it was shown that, due to unequal crossing-over during meiosis, there was an evolution from a chromothriptic rearrangement in the mother to another complex rearrangement involving both deletions and duplications in her daughter (48). Slamova et al (49) studied the case of a boy with developmental and growth delay in whom karyotyping showed a seemingly balanced de novo complex rearrangement of 4 chromosomes.…”

Section: Cnvs and Constitutional Chromothripsismentioning

confidence: 99%

Copy number variations and constitutional chromothripsis (Review)

2020

View full text Add to dashboard Cite

Both copy number variations (CNVs) and chromothripsis are phenomena that involve complex genomic rearrangements. Chromothripsis results in CNVs and other structural changes. CNVs are frequently observed in the human genome. Studies on CNVs have been increasing exponentially; the Database of Genomic Variants shows an increase in the number of data published on structural variations added to the database in the last 15 years. CNVs may be a result of replicative and non-replicative mechanisms, and are hypothesized to serve important roles in human health and disease. Chromothripsis is a phenomena of chromosomal rearrangement following chromosomal breaks at multiple locations and involves impaired DNA repair. In 2011, Stephens et al coined the term chromothripsis for this type of fragmenting event. Several proposed mechanisms have been suggested to underlie chromothripsis, such as p53 inactivation, micronuclei formation, abortive apoptosis and telomere fusions in telomere crisis. Chromothripsis gives rise to normal or abnormal phenotypes. In this review, constitutional chromothripsis, which may coexist with multiple de novo CNVs are described and discussed. This reviews aims to summarize recent advances in our understanding of CNVs and chromothripsis, and describe the effects of these phenomena on human health and birth defects.

show abstract

Flanking complex copy number variants in the same family formed through unequal crossing-over during meiosis

Cited by 6 publications

References 23 publications

The Iceberg under Water: Unexplored Complexity of Chromoanagenesis in Congenital Disorders

The Iceberg under Water: Unexplored Complexity of Chromoanagenesis in Congenital Disorders

Gynoecy instability in cucumber (Cucumis sativus L.) is due to unequal crossover at the copy number variation-dependent Femaleness (F) locus

Copy number variations and constitutional chromothripsis (Review)

Contact Info

Product

Resources

About