Chromothripsis: potential origin in gametogenesis and preimplantation cell divisions. A review

Pellestor, Franck; Gatinois, Vincent; Puechberty, Jacques; Geneviève, David; Lefort, Geneviève

doi:10.1016/j.fertnstert.2014.09.006

Cited by 62 publications

(73 citation statements)

References 126 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other breakpoints have small deletions (up to 70 bp), insertions (1-7 bp), or inversions, but do not have duplications (Supplemental Table S2). Similar breakpoint junction characteristics and "mostly balanced" copy number have been described at other chromothripsis rearrangements (Kloosterman et al 2011(Kloosterman et al , 2012Chiang et al 2012;Macera et al 2014;Nazaryan et al 2014;Pellestor et al 2014;de Pagter et al 2015). In EGL302 and two other chromothripsis events in the literature, breakpoints disrupt the PTPRD gene on Chromosome 9 (Macera et al 2014;de Pagter et al 2015), suggesting that this locus may be a chromothripsis hotspot.…”

Section: Complex Translocations and Chromothripsissupporting

confidence: 63%

“…Rarer translocations between four or five chromosomes proved to have tens of breakpoints, most of which were not recognized by standard cytogenetic methods. Combined with other complex chromosome rearrangement studies (Borg et al 2005;Kloosterman et al 2011Kloosterman et al , 2012Chiang et al 2012;Macera et al 2014;Pellestor et al 2014), these data suggest that translocations involving more than two chromosomes are likely to be the product of chromothripsis.…”

Section: Translocation Annotation and Technical Limitationssupporting

confidence: 55%

“…Thus, it is unlikely that most translocations have cryptic complexity. Chromothripsis is estimated to occur in 2-4% of cancers (Forment et al 2012;Pellestor et al 2014), which is similar to the incidence of chromothripsis in germline chromosome rearrangements (Kloosterman et al 2011;Chiang et al 2012;Forment et al 2012;Macera et al 2014).…”

Section: Translocation Annotation and Technical Limitationsmentioning

confidence: 87%

“…Though most germline translocations involve only two chromosomes, some are the product of many breakpoints on three to five different chromosomes. Originally seen in cancer (Stephens et al 2011), chromosome shattering or chromothripsis is now recognized as a cause of some germline translocations (Kloosterman et al 2011(Kloosterman et al , 2012Chiang et al 2012;Nazaryan et al 2014;Pellestor et al 2014;de Pagter et al 2015). …”

Section: [Supplemental Materials Is Available For This Article]mentioning

confidence: 99%

“…EGL302, EGL305, and EGL321 have translocations between at least four different chromosomes and many balanced insertions with altering orientations, all of which had blunt ends or microhomology at the junction. These features are hallmarks of chromothripsis (Kloosterman et al 2011(Kloosterman et al , 2012Chiang et al 2012;Pellestor et al 2014).…”

Section: Complex Translocations and Chromothripsismentioning

confidence: 99%

See 4 more Smart Citations

Unbalanced translocations arise from diverse mutational mechanisms including chromothripsis

2015

View full text Add to dashboard Cite

Unbalanced translocations are a relatively common type of copy number variation and a major contributor to neurodevelopmental disorders. We analyzed the breakpoints of 57 unique unbalanced translocations to investigate the mechanisms of how they form. Fifty-one are simple unbalanced translocations between two different chromosome ends, and six rearrangements have more than three breakpoints involving two to five chromosomes. Sequencing 37 breakpoint junctions revealed that simple translocations have between 0 and 4 base pairs (bp) of microhomology (n = 26), short inserted sequences (n = 8), or paralogous repeats (n = 3) at the junctions, indicating that translocations do not arise primarily from nonallelic homologous recombination but instead form most often via nonhomologous end joining or microhomology-mediated break-induced replication. Three simple translocations fuse genes that are predicted to produce in-frame transcripts of SIRPG-WWOX, SMOC2-PROX1, and PIEZO2-MTA1, which may lead to gain of function. Three complex translocations have inversions, insertions, and multiple breakpoint junctions between only two chromosomes. Whole-genome sequencing and fluorescence in situ hybridization analysis of two de novo translocations revealed at least 18 and 33 breakpoints involving five different chromosomes. Breakpoint sequencing of one maternally inherited translocation involving four chromosomes uncovered multiple breakpoints with inversions and insertions. All of these breakpoint junctions had 0-4 bp of microhomology consistent with chromothripsis, and both de novo events occurred on paternal alleles. Together with other studies, these data suggest that germline chromothripsis arises in the paternal genome and may be transmitted maternally. Breakpoint sequencing of our large collection of chromosome rearrangements provides a comprehensive analysis of the molecular mechanisms behind translocation formation.

show abstract

Section: Complex Translocations and Chromothripsissupporting

confidence: 63%

Section: Translocation Annotation and Technical Limitationssupporting

confidence: 55%

Section: Translocation Annotation and Technical Limitationsmentioning

confidence: 87%

Section: [Supplemental Materials Is Available For This Article]mentioning

confidence: 99%

Section: Complex Translocations and Chromothripsismentioning

confidence: 99%

See 3 more Smart Citations

Unbalanced translocations arise from diverse mutational mechanisms including chromothripsis

2015

View full text Add to dashboard Cite

show abstract

Very short DNA segments can be detected and handled by the repair machinery during germline chromothriptic chromosome reassembly

et al. 2018

View full text Add to dashboard Cite

Analyses at nucleotide resolution reveal unexpected complexity of seemingly simple and balanced chromosomal rearrangements. Chromothripsis is a rare complex aberration involving local shattering of one or more chromosomes and reassembly of the resulting DNA segments. This can influence gene expression and cause abnormal phenotypes. We studied the structure and mechanism of a seemingly balanced de novo complex rearrangement of four chromosomes in a boy with developmental and growth delay. Microarray analysis revealed two paternal de novo deletions of 0.7 and 2.5 Mb at two of the breakpoints in 1q24.3 and 6q24.1-q24.2, respectively, which could explain most symptoms of the patient. Subsequent whole-genome mate-pair sequencing confirmed the chromothriptic nature of the rearrangement. The four participating chromosomes were broken into 29 segments longer than 1 kb. Sanger sequencing of all breakpoint junctions revealed additional complexity compatible with the involvement of different repair pathways. We observed translocation of a 33 bp long DNA fragment, which may have implications for the definition of the lower size limit of structural variants. Our observations and literature review indicate that even very small fragments from shattered chromosomes can be detected and handled by the repair machinery during germline chromothriptic chromosome reassembly.

show abstract

Uniparental disomy: Origin, frequency, and clinical significance

Benn

2021

Prenatal Diagnosis

View full text Add to dashboard Cite

Uniparental disomy (UPD) is defined as two copies of a whole chromosome derived from the same parent. There can be multiple mechanisms that lead to UPD; these are reviewed in the context of contemporary views on the mechanism leading to aneuploidy. Recent studies indicate that UPD is rare in an apparently healthy population and also rare in spontaneous abortion tissues. The most common type of UPD is a maternal heterodisomy (both maternal allele sets present). Isodisomy (a duplicated single set of alleles) or segmental loss of heterozygosity is sometimes encountered in SNP‐based microarray referrals. Decisions regarding the most appropriate follow‐up testing should consider the possibility of consanguinity (that will generally involve multiple regions), an imprinted gene disorder (chromosomes 6, 7, 11, 14, 15, 20), expression of an autosomal recessive disorder, and an occult aneuploid cell line that may be confined to the placenta. Upd(16)mat, per se, does not appear to be associated with an abnormal phenotype. UPD provides an insight into the history of early chromosome segregation error and understanding the rates and fate of these events are of key importance in the provision of fertility management and prenatal healthcare.

show abstract

Chromothripsis: potential origin in gametogenesis and preimplantation cell divisions. A review

Cited by 62 publications

References 126 publications

Unbalanced translocations arise from diverse mutational mechanisms including chromothripsis

Unbalanced translocations arise from diverse mutational mechanisms including chromothripsis

Very short DNA segments can be detected and handled by the repair machinery during germline chromothriptic chromosome reassembly

Uniparental disomy: Origin, frequency, and clinical significance

Contact Info

Product

Resources

About