Mosaic inv dup(8p) marker chromosome with stable neocentromere suggests neocentromerization is a post-zygotic event
✍ Scribed by Voullaire, Lucille ;Saffery, Richard ;Earle, Elizabeth ;Irvine, Danielle V. ;Slater, Howard ;Dale, Sue ;du Sart, Desiree ;Fleming, Tracy ;Choo, K.H. Andy
- Publisher
- John Wiley and Sons
- Year
- 2001
- Tongue
- English
- Weight
- 485 KB
- Volume
- 102
- Category
- Article
- ISSN
- 0148-7299
No coin nor oath required. For personal study only.
✦ Synopsis
Marker chromosomes containing active human neocentromeres have been described in individuals where the chromosomes are non-mosaic, suggesting that they are mitotically stable, but also in individuals where there is mosaicism, raising the possibility of neocentromere instability. We report two independently ascertained individuals who are mosaic for a supernumerary marker chromosome, shown by reverse chromosome painting to have an 8p origin, resulting in mosaicism for tetrasomy 8p23.1!pter in the patient. The markers have a primary constriction but show no detectable centromeric a-satellite DNA. The marker in Patient 1 demonstrated no centromere protein CENP-B binding, but associated with nine different functionally critical centromere proteins. Investigation of peripheral blood lymphocytes from this patient on ®ve separate occasions over a 13year period showed 23±46% mosaicism for the marker chromosome with no decrease in incidence. In vitro investigation of primary and secondary sub-clones of a lymphoblast cell line derived from the patient demonstrated 100% stability of the marker chromosome indicating that neocentromere instability is unlikely to be responsible for the mosaicism in the patient. This and other available data support a general model of neocentromerization as a post-zygotic event, irrespective of whether the super-numerary chromosome fragment has arisen during meiosis or post-fertilization at mitosis.