Research output per year
Research output per year
Mirjam S. de Pagter, Markus J. van Roosmalen, AF Baas, I.J. Renkens, KJ Duran, E van Binsbergen, Masoumeh Tavakoli-Yaraki, Ron Hochstenbach, Lars T. van der Veken, Edwin Cuppen, Wigard P. Kloosterman*
Research output: Contribution to journal › Article › Academic › peer-review
Chromothripsis represents an extreme class of complex chromosome rearrangements ( CCRs) with major effects on chromosomal architecture. Although recent studies have associated chromothripsis with congenital abnormalities, the incidence and pathogenic effects of this phenomenon require further investigation. Here, we analyzed the genomes of three families in which chromothripsis rearrangements were transmitted from a mother to her child. The chromothripsis in the mothers resulted in completely balanced rearrangements involving 8-23 breakpoint junctions across three to five chromosomes. Two mothers did not show any phenotypic abnormalities, although 3-13 protein-coding genes were affected by breakpoints. Unbalanced but stable transmission of a subset of the derivative chromosomes caused apparently de novo complex copy-number changes in two children. This resulted in gene-dosage changes, which are probably responsible for the severe congenital phenotypes of these two children. In contrast, the third child, who has a severe congenital disease, harbored all three chromothripsis chromosomes from his healthy mother, but one of the chromosomes acquired de novo rearrangements leading to copy-number changes. These results show that the human genome can tolerate extreme reshuffling of chromosomal architecture, including breakage of multiple protein-coding genes, without noticeable phenotypic effects. The presence of chromothripsis in healthy individuals affects reproduction and is expected to substantially increase the risk of miscarriages, abortions, and severe congenital disease.
Original language | English |
---|---|
Pages (from-to) | 651-656 |
Number of pages | 6 |
Journal | American Journal of Human Genetics |
Volume | 96 |
Issue number | 4 |
DOIs | |
Publication status | Published - 2 Apr 2015 |
Research output: Contribution to conference › Abstract › Other research output
Research output: Contribution to conference › Abstract › Other research output
Mirjam de Pagter (Speaker)
Activity: Talk or presentation › Oral presentation › Academic
Mirjam de Pagter (Speaker)
Activity: Talk or presentation › Oral presentation › Academic