Trisomy 20p resulting from inverted duplication and neocentromere formation

Voullaire, Lucille; Saffery, Richard; Davies, J. L.; Earle, Elizabeth D.; Kalitsis, Paul; Slater, Howard R.; Irvine, Danielle V.; Choo, K.H. Andy

doi:10.1002/(sici)1096-8628(19990806)85:4<403::aid-ajmg18>3.0.co;2-r

Cited by 35 publications

(14 citation statements)

References 28 publications

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“…2d) were present at a similar location to the CREST signal. CENP-B is not expected to be detected at a Y chromosome centromere, but is also absent from other neocentromeres (Voullaire et al 1993(Voullaire et al , 1999, so its lack is not surprising and may account for the low CREST signal. Thus this rearranged Y chromosome contains a functional neocentromere located near the breakpoint in Yq11.2 that carries an active kinetochore, as shown by the presence of the kinetochore proteins CENP-A, -C and -E. In addition, the presence of Mad2 at the neocentromere (in these Colcemid-treated cells) suggests that it is also competent to activate the spindle assembly checkpoint.…”

Section: Resultsmentioning

confidence: 99%

A neocentromere in the DAZ region of the human Y chromosome

Floridia

Gimelli

Zuffardi³

et al. 2000

Chromosoma

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We describe a novel rearranged human Y chromosome consisting of an inverted duplication of the long arm heterochromatin and a small amount of euchromatin: rea(Y)(qter-q11.2::q11.2-qter). The normal centromere has been deleted and a neocentromere containing CENP-A, -C, -E and Mad2 but not CENP-B has formed close to the breakpoint. A 2.7 Mb yeast artificial chromosome contig spanning the breakpoint was constructed and the breakpoint was localised to a region of <120 kb close to the DAZ gene cluster. Combined immunofluorescence and fluorescence in situ hybridisation showed that the centromeric protein-binding domain of the neocentromere was located near the breakpoint and within the DAZ cluster.

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Section: Resultsmentioning

confidence: 99%

A neocentromere in the DAZ region of the human Y chromosome

Floridia

Gimelli

Zuffardi³

et al. 2000

Chromosoma

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“…These neocentromeres arise in intact chromosomes and functionally replace the normal centromere. The old centromere appears unchanged but functionally inactivated, as proved by the absence of CENP-A and other centromere-specific proteins that are conversely present at the new centromeric site (Warburton et al, 1997;Voullaire et al, 1999). They do not cause clinical problems and, indeed, were discovered serendipitously, mostly through amniocentesis.…”

Section: Human Neocentromeresmentioning

confidence: 99%

Centromere repositioning in mammals

et al. 2011

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The evolutionary history of chromosomes can be tracked by the comparative hybridization of large panels of bacterial artificial chromosome clones. This approach has disclosed an unprecedented phenomenon: 'centromere repositioning', that is, the movement of the centromere along the chromosome without marker order variation. The occurrence of evolutionary new centromeres (ENCs) is relatively frequent. In macaque, for instance, 9 out of 20 autosomal centromeres are evolutionarily new; in donkey at least 5 such neocentromeres originated after divergence from the zebra, in less than 1 million years. Recently, orangutan chromosome 9, considered to be heterozygous for a complex rearrangement, was discovered to be an ENC. In humans, in addition to neocentromeres that arise in acentric fragments and result in clinical phenotypes, 8 centromererepositioning events have been reported. These 'real-time' repositioned centromere-seeding events provide clues to ENC birth and progression. In the present paper, we provide a review of the centromere repositioning. We add new data on the population genetics of the ENC of the orangutan, and describe for the first time an ENC on the X chromosome of squirrel monkeys. Next-generation sequencing technologies have started an unprecedented, flourishing period of rapid whole-genome sequencing. In this context, it is worth noting that these technologies, uncoupled from cytogenetics, would miss all the biological data on evolutionary centromere repositioning. Therefore, we can anticipate that classical and molecular cytogenetics will continue to have a crucial role in the identification of centromere movements. Indeed, all ENCs and human neocentromeres were found following classical and molecular cytogenetic investigations. Heredity (2012) 108, 59-67; doi:10.1038/hdy.2011.101; published online 2 November 2011 Keywords: neocentromeres; mammals; centromere movements; evolutionary new centromeres; evolution INTRODUCTIONThe centromere is a complex chromosomal structure responsible for proper chromosome/chromatid segregation at meiosis and mitosis. In almost all eukaryotes, centromeres are found at specific locations along chromosomes and are composed of, occasionally very large, blocks of satellite DNA. Evidence shows that in spite of the very high conservation of centromeric proteins (CENP), the satellite DNA sequences can substantially differ even among closely related species. Recently, two interconnected phenomena, human neocentromeres (HN) and evolutionary new centromeres (ENC, also called repositioned centromeres), have revolutionized our understanding of centromere function and its relationship to the underlining DNA sequences. HNs are centromeres that emerge in ectopic chromosomal regions and are devoid of alphoid sequences, that is, the satellite DNA present at primate centromeres. ENCs are centromeres that move to a new position along the chromosome without any change in marker order (no inversion or other structural rearrangements).

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“…We produced several stably transfected human cell lines expressing EGFP-CENP-A fusion protein each of which contained a di¡erent neocentric marker chromosome as follows: a 58-Mb marker derived from chromosome 10 designated mardel (10) (Voullaire et al 1993); a 0.7-Mb truncated derivative of mardel(10) designated MiC5 (Sa¡ery et al 2001); a 40-Mb inverted duplication of chromosome 20p designated invdup(20p) (Voullaire et al 1999); and a 'giant rod' chromosome designated LGR identi¢ed in a liposarcoma (Pedeutour et al 1999).…”

Section: Faithful Non-biased Incorporation Of Egfp-cenp-a Into Human mentioning

confidence: 99%

Chromosome size and origin as determinants of the level of CENP-A incorporation into human centromeres

et al. 2004

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We have expressed an EGFP-CENP-A fusion protein in human cells in order to quantitate the level of CENP-A incorporated into normal and variant human centromeres. The results revealed a 3.2-fold difference in the level of CENP-A incorporation into alpha-satellite repeat DNA-based centromeres, with the Y centromere showing the lowest level of all normal human chromosomes. Identification of individual chromosomes revealed a statistically significant, though not absolute, correlation between chromosome size and CENP-A incorporation. Analysis of three independent neocentromeres revealed a significantly reduced level of CENP-A compared to normal centromeres. Truncation of a neocentric marker chromosome to produce a minichromosome further reduced CENP-A levels, indicating a remodelling of centromeric chromatin. These results suggest a role for increased CENP-A incorporation in the faithful segregation of larger chromosomes and support a model of centromere evolution in which neocentromeres represent ancestral centromeres that, through adaptive evolution, acquire satellite repeats to facilitate the incorporation of higher numbers of CENP-A containing nucleosomes, thereby facilitating the assembly of larger kinetochore structures.

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Trisomy 20p resulting from inverted duplication and neocentromere formation

Cited by 35 publications

References 28 publications

A neocentromere in the DAZ region of the human Y chromosome

A neocentromere in the DAZ region of the human Y chromosome

Centromere repositioning in mammals

Chromosome size and origin as determinants of the level of CENP-A incorporation into human centromeres

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