32
EIGIL KJELDSEN and STEEN K0LVRAA
rearrangements involving these regions is a new area of genetic disorders
(involving mental retardation and mild to severe dysmorphism) that involves both balanced and unbalanced rearrangements. FISH using telomeric probes specific for each chromosome-arm can been used to detect
such abnormalities in subjects who apparently had normal karyotypes by
conventional banding methods (Flint et al 1995, Giraudeau et al. 1997).
These terminal segmental aneusomies have been termed telomere syndromes and may account for 10-15% of mentally retarded children having
normal banding analyses. Imbalances or rearrangements involving the
subtelomeric regions have also been identified in malignancy. Figure
4G shows an example of a ring chromosome 3 that has lost both subtelomeric regions.
II. Characterization of cryptic chromosomal aberrations (whole genome screening). In a historic perspective it was a major breakthrough in
1956 when it was established that man has 46 human chromosomes (Fig.
5A) allowing for a new type of method to screen the whole genome. Refinements of the chromosome preparation techniques allowed a grouping
of the chromosomes by size (Fig. 5B) and when banding techniques in the
early 1970s were established, it became possible to characterize each individual chromosome (Fig. 5C,D). The development of FISH-techniques
(Fig. 4) was encouraged by an ever-increasing number of identified but yet
uncharacterized chromosomal aberrations such as simple or complex
translocations and the presence of marker and derivative chromosomes.
These classic FISH techniques allowed characterization of specific chromosomal rearrangements which was soon followed by the development of
multi-color FISH techniques that, in a single hybridization experiment,
allowed for both identification and characterization of several types of
chromosome aberrations. In a multi-color approach with a few painting
probes one must, however, have a clue as to which chromosomes are involved in an aberration, whereas with the more recent refinements of the
FISH-techniques such as 24-color karyotyping or CGH-analysis, one can
rapidly and reliable screen for many types of chromosomal aberrations
and imbalances, without prior knowledge of the involved chromosomes.
In clinical genetics and oncology translocations ranging from simple
(involving two chromosomes) to complex rearrangements (involving
three or more chromosomes) is another area where 24-color karyotyping
has proven valuable (Rao et a1. 1998, Veldman et a1. 1997). These types of
chromosomal rearrangements cannot be identified by CGH-analysis, that
on the other hand, is efficient in identifying genomic imbalances such as
deletions or amplifications (Kallioniemi et a1.1992). Figure 5E shows an
example of a trisomy for chromosome 18 detected by CGH-analysis.
EIGIL KJELDSEN and STEEN K0LVRAA
rearrangements involving these regions is a new area of genetic disorders
(involving mental retardation and mild to severe dysmorphism) that involves both balanced and unbalanced rearrangements. FISH using telomeric probes specific for each chromosome-arm can been used to detect
such abnormalities in subjects who apparently had normal karyotypes by
conventional banding methods (Flint et al 1995, Giraudeau et al. 1997).
These terminal segmental aneusomies have been termed telomere syndromes and may account for 10-15% of mentally retarded children having
normal banding analyses. Imbalances or rearrangements involving the
subtelomeric regions have also been identified in malignancy. Figure
4G shows an example of a ring chromosome 3 that has lost both subtelomeric regions.
II. Characterization of cryptic chromosomal aberrations (whole genome screening). In a historic perspective it was a major breakthrough in
1956 when it was established that man has 46 human chromosomes (Fig.
5A) allowing for a new type of method to screen the whole genome. Refinements of the chromosome preparation techniques allowed a grouping
of the chromosomes by size (Fig. 5B) and when banding techniques in the
early 1970s were established, it became possible to characterize each individual chromosome (Fig. 5C,D). The development of FISH-techniques
(Fig. 4) was encouraged by an ever-increasing number of identified but yet
uncharacterized chromosomal aberrations such as simple or complex
translocations and the presence of marker and derivative chromosomes.
These classic FISH techniques allowed characterization of specific chromosomal rearrangements which was soon followed by the development of
multi-color FISH techniques that, in a single hybridization experiment,
allowed for both identification and characterization of several types of
chromosome aberrations. In a multi-color approach with a few painting
probes one must, however, have a clue as to which chromosomes are involved in an aberration, whereas with the more recent refinements of the
FISH-techniques such as 24-color karyotyping or CGH-analysis, one can
rapidly and reliable screen for many types of chromosomal aberrations
and imbalances, without prior knowledge of the involved chromosomes.
In clinical genetics and oncology translocations ranging from simple
(involving two chromosomes) to complex rearrangements (involving
three or more chromosomes) is another area where 24-color karyotyping
has proven valuable (Rao et a1. 1998, Veldman et a1. 1997). These types of
chromosomal rearrangements cannot be identified by CGH-analysis, that
on the other hand, is efficient in identifying genomic imbalances such as
deletions or amplifications (Kallioniemi et a1.1992). Figure 5E shows an
example of a trisomy for chromosome 18 detected by CGH-analysis.