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Clinical Vignettes

Vignette 2: The Power of FISH

Here are examples of how FISH technology assists in interpreting array CGH results. Note that in each example, the array CGH finding is identical, but the FISH results are completely different.

Example 1: Abnormal microarray showing DNA dosage gain on chromosome 17p11.2.

FISH analyses of both interphase and metaphase cells demonstrate a gain (duplication) of the red probe used to represent the region of DNA dosage gain on the microarray (Figure 1). Interphase FISH clearly demonstrates three distinct signals. Metaphase FISH consistently demonstrates one red signal with greater intensity for all cells analyzed, signifying a duplication on chromosome 17p. The green signals represent control FISH probes for the subtelomeric long arm of chromosome 17.

Figure 1. (A) Microarray plot showing DNA dosage gain on chromosome 17p11.2. (B) Metaphase FISH image showing duplication of 17p11.2. The clone from 17p11.2 is labeled in green, and a subtelomere probe from the short arm of chromosome 17 is labeled in green as a control. One red signal shows greater intensity, indicating a duplication.

Example 2: Abnormal microarray showing DNA dosage gain on chromosome 17p11.2.

FISH analyses of both interphase and metaphase cells demonstrate a gain (duplication) of the red probe used to represent the region of DNA dosage gain on the microarray (Figure 2). Interphase FISH clearly demonstrates three distinct signals. Metaphase FISH demonstrates two normal 17 chromosomes in addition to a marker chromosome 17p (also called a derivative 17p). The green signals represent control FISH probes for the subtelomeric long arm of chromosome 17.

Figure 2. (A) Microarray plot showing DNA dosage gain on chromosome 17p11.2. (B) Metaphase FISH image showing marker chromosome 17p. The clone from 17p11.2 is labeled in green and a subtelomere probe from the short arm of chromosome 17 is labeled in green as a control. Metaphase FISH demonstrates two normal 17 chromsosomes in addition to a marker chromsosome 17p.

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