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

Publisher Website
Google Scholar
Abstract
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 α‐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 five separate occasions over a 13‐year 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 supernumerary chromosome fragment has arisen during meiosis or post‐fertilization at mitosis.