FAMILY WITH 22-DERIVED MARKER CHROMOSOME AND LATE-ONSET DEMENTIA OF THE ALZHEIMER-TYPE .2. FURTHER CYTOGENETIC ANALYSIS OF THE MARKER AND CHARACTERIZATION OF THE HIGH-LEVEL REPEAT SEQUENCES USING FLUORESCENCE IN-SITU HYBRIDIZATION

We have further characterized an unusual 22p + marker chromosome with a double nucleolus organizer region (dNOR) previously identified in a family with late-onset dementia of the Alzheimer type. G-banding and m orphology of the marker's q arm were typically normal. However, the p + arm had a terminal cytological satellite and a GT-positive region at the midpoint. Standard C-banding documented 2 C-positive regions: one was associated with the primary centromere; the other, which was at t he midpoint of the p arm, was not associated with a constriction. With replication-banding, there was a darkly staining region in the middle of the p + arm that resembled the pericentromeric region of a chromos ome 21 or 22. Fluorescence in situ hybridization with pXlr 101, a prob e recognizing the full repeating unit of rDNA, indicated that the mark er had an unusually large rDNA region; with pU 1.2, a probe recognizin g the human rDNA promoter, the signal was a doublet. The marker had 2 signals with a beta-satellite probe, and a second signal in addition t o that present at the primary centromere under low stringency with alp ha-satellite probes and a classic satellite probe. Immunostaining of c hromosome spreads after R-banding and ultraviolet (UV) denaturation sh owed that the major portion of the marker's p arm was highly methylate d. (C) 1993 Wiley-Liss, Inc.