Mosaic inv dup(8p) marker chromosome with stable neocentromere suggests neocentromerization is a post-zygotic event

Marker human neocentromeres have been described in individuals where the ch romosomes are non-mosaic, suggesting that they are mitotically stable, but also in individuals where there is mosaicism, raising the possibility of ne ocentromere instability. We report two independently ascertained individual s who are mosaic for a supernumerary marker chromosome, shown by reverse ch romosome painting to have an 8p origin, resulting in mosaicism for tetrasom y 8p23.1-->pter in the patient. The markers have a primary constriction but show no detectable centromeric or-satellite DNA, The marker in Patient 1 d emonstrated no centromere protein CENP-B binding, but associated with nine different functionally critical centromere proteins. Investigation of perip heral blood lymphocytes from this patient on five separate occasions over a 13-year period showed 23-46% mosaicism for the marker chromosome with no d ecrease in incidence. In vitro investigation of primary and secondary sub-c lones of a lymphoblast cell line derived from the patient demonstrated 100% stability of the marker chromosome indicating that neocentromere instabili ty is unlikely to be responsible for the mosaicism in the patient. This and other available data support a general model of neocentromerization as a p ost-zygotic event, irrespective of whether the supernumerary chromosome fra gment has arisen during meiosis or post-fertilization at mitosis. (C) 2001 Wiley-Liss, Inc.