Acrocentric p-arms Probe Combination

The Nucleolar Organiser Regions (NOR)s contain clusters of genes which code for the three largest structural rRNA molecules (5.8S, 18S, and 28S) . These genes, rDNA, are critically important for the viability of the cell and represent around 0.5% of the human diploid genome. They are found in the short arm of the acrocentric chromosomes and are the region around which the nucleoli develop at the end of mitosis¹.

A NOR can translocate to a terminal region of another chromosome. In rare instances this can be pathogenic, particularly when the translocation has led to a deletion at the tip of recipient chromosome². In addition, the rDNA genes are unstable and subject to a high degree of mitotic recombination, leading to a huge variation in size across the bands 13p12, 14p12, 15p12, 21p12 and 22p12, though this size is best measured at the molecular level. It has been suggested that the restructuring of the rDNA genes is the most common chromosomal alteration in adult solid tumours³.

In routine cytogenetic analysis, NORs can be used to delineate marker chromosomes, through a process of silver staining the NOR (known as AgNOR staining⁴). The process utilises the acidic nature of the nascent ribosomal RNA translated from the rDNA genes to generate silver grains at the site of the translation (the NOR) which are thus made visible in standard, block stained, cytogenetic preparations. However, the technique relies on translation of protein and if this is not present conventional silver staining will not stain the NOR. Recently, a FISH probe has been developed that is able to overcome this problem so that presence of the acrocentric chromosomes in the marker can be accurately confirmed (the most common chromosomes deriving marker chromosomes are the acrocentric D & G groups, with chromosome 15 alone being present in around 70% of marker chromosomes) ⁵.

Reference:/Bibliographie/Literatur/Bibliografia

1. 1. McClintock B 1934 Z Zellforsch 21:294-326
2. R. J. M. Gardner, Grant R. Sutherland -Chromosome abnormalities and genetic counseling 2004 - p240
3. Stults, DM et al Human rRNA Gene Clusters Are Recombinational Hotspots in Cancer. Cancer Res 2009; 69: (23). December 1, 2009 9096 -9104
4. GOODPASTURE C, BLOOM SE: Visualization of nucleolar organizer regions in mammalian chromosomes using silver staining. Chromosoma 53:37-50, 1975
5. Babu V et al 2005 Ind J Hum Genet 11(1): 44-46