The Principles of Clinical Cytogenetics - Extra Materials - Springer

460 Daynna Wolff and Stuart Schwartz
Fig. 3. Example of FISH to a single-copy target using a cosmid (SNRPN) to the Prader–Willi “critical
region” localized to 15q11-13. (A) A metaphase in which 1 normal chromosome 15 has 3 hybridization signals
from a centromeric control probe (green), a distal control probe (red), and a probe to the critical region (red).
The other chromosome 15 (arrow) revealed hybridization signals only for the two control probes. Thus, this
chromosome was deleted for the critical region and this patient was diagnosed with Prader–Willi syndrome.
Chromosomes were counterstained blue with DAPI. (B) In this partial metaphase, a SNRPN probe and control
probe (both red) were utilized. Chromosomes were counterstained orange with propidium iodide. The arrow
indicates the chromosome 15 with a duplicated SNRPN signal. This patient was referred for a diagnosis of
autism.
of abnormalities in the telomeric regions that are not visualized well with G-banding and were historically
studied with R- or T-banding, are difficult. Given that these regions are gene rich, they have
particular relevance for clinical studies.
Located immediately proximal to the terminal telomeric repeated DNA segment is a telomereassociated
repeat (TAR). Homologous recombination within both the telomeric regions and TAR can
cause deletions and duplications of the adjacent unique DNA sequence (subtelomeric sequences).
FISH probes consisting of unique sequences of DNA from the subtelomeric region approximately
100–300 kb from the end of each human chromosome have been developed, with a few exceptions;
there are no probes for the individual acrocentric short arms and Xp and Yp share similar sequences,
as do Xq and Yq. Subtelomeric probes are available individually or, as described by Knight et al.
(15), as part of a “multiprobe coverslip device.” In this system, all of the probes are placed onto 24
squares on a device that is hybridized to cells on a single slide (see Fig. 4).
Aberrations of the subtelomeric regions have been documented in a significant percentage of
patients with idiopathic mental retardation with an overall frequency of approximately 5% (range of
0–13.3%) (16,17) (see Table 2). The majority of studies of abnormalities in the subtelomeric regions