Biomedical Engineering Reference
In-Depth Information
the autosomal dominant form of SVAS to this locus. Further studies showed
that the mutated gene in SVAS was involved in forming elastin. Using FISH
technology, it has been found that more than 90% of the Williams patients
have a visible deletion in this locus and molecular studies confi rm these
patients with mutations in elastin, explaining their SVAS. Several other
genes are also deleted in Williams syndrome. It is possible that the use of
deletion mapping of different Williams patients having just some of the fea-
tures of Williams, can be correlated to the degree of deletion seen in these
patients. This type of study would help to identify these other genes and to
correlate their loss to the various phenotypical features of the disorder.
Other contiguous gene disorders are seen in Table 7.2 along with their
chromosome location and their phenotypic effects.
7.6
Methods of detection of cytogenetic mutations
Chromosome analysis is performed using rapidly dividing cells from tissue
culture or on highly active tissue sources such as tumor cells. The analy-
sis is on either metaphase or prophase cells that have been arrested with
chemical agents like colcemid. Various types of cell cultures can be stud-
ied. These include short-term peripheral blood cultures (usually three days)
and long-term cultures (seven days or more) from skin fi broblasts. Prenatal
diagnosis methods use amniocytes and chorionic villi cells from fetal biop-
sies. Tumor samples can examine the chromosome complement of various
solid tumors and relatively quick direct cytogenetic methods are often used
with bone marrow cells.
All these procedures take advantage of the increase in the number of
actively dividing cells that tissue culture methods can produce and employ
several different microscopic techniques that improve resolution so that
small changes to the structure of the chromosomes can be detected. Table 7.3
shows the more common banding methods and the types of treatments
that are needed to produce them. All chromosome-banding techniques
take advantage of the underlying coiled nature of the chromatin within the
eukaryotic chromosome and/or the affi nity of certain stains for euchromatic
and heterochromatic chromosome areas. They have been used since the
early 1970s and their use has led to the discovery of numerous chromosome
abnormalities in dysmorphic individuals. They have become an invaluable
tool for the identifi cation and prognosis of a large number of malignancies.
7. 6 .1 G banding
G banding
, which uses a trypsin pre-treatment of the slide followed by stain-
ing with Giemsa, is the one that is typically done fi rst to rule out major
