A neocentromere on human chromosome 3 without detectable α-satellite DNA forms morphologically normal kinetochores

Wandall, Annelise; Tranebjærg, Lisbeth; Tommerup, Niels

doi:10.1007/s004120050319

Cited by 38 publications

(38 citation statements)

References 48 publications

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“…A neocentromere at 3q26 was observed in a father, mildly mentally retarded, and his daughter, on an abnormal chromosome 3 lacking the centromeric region that appeared excised to form a supernumerary minichromosome, as already described (Wandall et al 1998). His parents were normal.…”

Section: Casementioning

confidence: 61%

“…No ␣-satellite DNA was detected, by FISH, at the 3q26 neocentromere. CREST immunotyping, reported by Wandall et al (1998), detected centromeric proteins at the neocentromere site (3q26). Reiterated FISH experiments using BAC clones as a probe were performed to precisely define the rearrangement that generated the two derivative chromosomes (D3a and D3b in the Fig.…”

Section: Casementioning

confidence: 98%

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Recurrent Sites for New Centromere Seeding

et al. 2004

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Using comparative FISH and genomics, we have studied and compared the evolution of chromosome 3 in primates and two human neocentromere cases on the long arm of this chromosome. Our results show that one of the human neocentromere cases maps to the same 3q26 chromosomal region where a new centromere emerged in a common ancestor of the Old World monkeys ∼25-40 million years ago. Similarly, the locus in which a new centromere was seeded in the great apes' ancestor was orthologous to the site in which a new centromere emerged in the New World monkeys' ancestor. These data suggest the recurrent use of longstanding latent centromeres and that there is an inherent potential of these regions to form centromeres. The second human neocentromere case (3q24) revealed unprecedented features. The neocentromere emergence was not accompanied by any chromosomal rearrangement that usually triggers these events. Instead, it involved the functional inactivation of the normal centromere, and was present in an otherwise phenotypically normal individual who transmitted this unusual chromosome to the next generation. We propose that the formation of neocentromeres in humans and the emergence of new centromeres during the course of evolution share a common mechanism

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Section: Casementioning

confidence: 61%

Section: Casementioning

confidence: 98%

Recurrent Sites for New Centromere Seeding

et al. 2004

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“…In two of the previously reported 'class II' cases, the deleted segments remained as linear structures. One of these fragments had undergone telomere capture and, as with the ring chromosomes, was also lost in only a small proportion of cells (10%), 5 while the other did not demonstrate telomeric sequences and was more frequently lost (62%) 17 suggesting that ring formation or telomere capture is necessary for stabilization of the deleted segment.…”

Section: Discussionmentioning

confidence: 99%

“…4 Moreover, recent cases have reported the inheritance of 'neocentromeric' chromosomes suggesting that they also have the capacity to function successfully during meiosis. 3,5 Neocentromeres are usually devoid of a-satellite DNA. However, studies to date suggest that they share the structural and behavioral characteristics of canonical centromeres; they associate with many functionally important centromere-specific proteins such as CENP-A and heterochromatin proteins (eg hHP1b), 1 they form normal end-on associations with kinetochores that have normal morphology and are the same size as kinetochores of other chromosomes of a comparable size 5 and replication timing is delayed to the third quarter of S phase (in line with other centromeres), once a neocentromere is activated.…”

Section: Introductionmentioning

confidence: 99%

“…3,5 Neocentromeres are usually devoid of a-satellite DNA. However, studies to date suggest that they share the structural and behavioral characteristics of canonical centromeres; they associate with many functionally important centromere-specific proteins such as CENP-A and heterochromatin proteins (eg hHP1b), 1 they form normal end-on associations with kinetochores that have normal morphology and are the same size as kinetochores of other chromosomes of a comparable size 5 and replication timing is delayed to the third quarter of S phase (in line with other centromeres), once a neocentromere is activated. 6 Preliminary analysis of the DNA sequence across neocentromeric regions suggests the presence of features that may predispose these sites to neocentromere formation: they have a high AT content (B65%, comparable with the AT content of a-satellite DNA), a high content of other repeat elements 6,7 and fewer SINES and potential genes than the surrounding region.…”

Section: Introductionmentioning

confidence: 99%

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Class II neocentromeres: a putative common neocentromere site in band 4q21.2

Warburton¹,

Splitt²,

Maxwell

et al. 2003

Eur J Hum Genet

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Neocentromeres are rare functional centromeres formed within noncentromeric chromosomal regions. We report the finding of a neocentromere in a very rare class II analphoid chromosome. This neocentromere was detected prenatally in a fetus with the karyotype: 47,XY,del(4)(p15.3q21.1), þ r(4)(p15.3q21.1).ish del(4)(D4S3360 þ ,WHS þ ,D4Z1À,4qsubtel þ ),r(4)(D4S3360À,WHSÀ,D4Z1 þ , 4qsubtelÀ)de novo. The fetus was missing one normal chromosome 4 but had a ring chromosome, consisting of the pericentromeric region of chromosome 4, and a deleted chromosome 4, the reciprocal product of the ring formation. In situ hybridization established that the chromosome 4 pericentromeric heterochromatin was located on the ring chromosome, while the Wolf-Hirschhorn critical region and chromosome 4 subtelomeric regions were present on the deleted chromosome. A C-band-negative constriction was observed in band 4q21.2 of the deleted chromosome 4, indicating that a neocentromere had been formed in this band, allowing stable segregation during cell division. This chromosome abnormality was detected in cultured amniocytes from a 20-week pregnancy presenting with intrauterine growth retardation and echogenic bowel. The pregnancy resulted in intrauterine death at 33 -34 weeks. Despite the apparently balanced karyotype, the fetus is likely to have been phenotypically impaired due to disruption of genes by the neocentromere, rearrangement and ring chromosome formation. There has been one previous report of neocentromere formation in band 4q21; the observation presented here might refine a putative common neocentromeric site to sub-band 4q21.2.

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Mosaic tetrasomy 8q: Inverted duplication of 8q23.3qter in an analphoid marker

et al. 2000

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We observed an analphoid marker chromosome stable through cell division in a 16-year-old girl with developmental delay, short stature, limb contractures, and ovaries containing multiple cysts. She also developed myasthenia gravis at 15 years. The marker chromosome, present in 75% of metaphases (and in 90% of transformed lymphoblastoid cells), was C-band negative, and had no pan alpha-satellite sequences detectable by fluorescence in situ hybridization (FISH). The 8q origin of the marker was determined by use of subtelomeric probes and was confirmed by chromosome 8 painting probes. The marker was shown to be an inversion duplication of 8q when subtelomeric, telomeric, and c-myc FISH probes hybridized to both ends of the marker. The karyotype was 47,XX,+inv dup(8)(qter--> q23.3::q23.3-->[neocen]-->qter), resulting in tetrasomy for 8q23.3qter. The parents had normal karyotypes. Centromeric proteins CENP-C and CENP-E were present, but alpha associated centromere protein CENP-B was absent at a position defining a neocentromere.

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A neocentromere on human chromosome 3 without detectable α-satellite DNA forms morphologically normal kinetochores

Cited by 38 publications

References 48 publications

Recurrent Sites for New Centromere Seeding

Recurrent Sites for New Centromere Seeding

Class II neocentromeres: a putative common neocentromere site in band 4q21.2

Mosaic tetrasomy 8q: Inverted duplication of 8q23.3qter in an analphoid marker

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