Family with 22-derived marker chromosome and late-onset dementia of the Alzheimer type: II. 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 morphology 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 the 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 chromosome 21 or 22. Fluorescence in situ hybridization with pXlr 101, a probe recognizing the full repeating unit of rDNA, indicated that the marker had an unusually large rDNA region; with pU 1.2, a probe recognizing the human rDNA promoter, the signal was a doublet. The marker had 2 signals with a β‐satellite probe, and a second signal in addition to that present at the primary centromere under low stringency with α‐satellite probes and a classic satellite probe. Immunostaining of chromosome spreads after R‐banding and ultraviolet (UV) denaturation showed that the major portion of the marker's p arm was highly methylated. © 1993 Wiley‐Liss, Inc.