Biomedical Engineering Reference
In-Depth Information
12
Applications of Matrix-CGH (Array-CGH)
for Genomic Research and Clinical Diagnostics
Carsten Schwaenena, Michelle Nesslinga, Bernhard Radlwimmera,
Swen Wessendorf, and Peter Lichtera
12.1 Introduction
One of the major scientific achievements of the past decade was the rapid
development of genomic research, resulting in the comprehensive sequence
information of the human genome. This information has provided the basis
for the identification of a vast number of novel genomic aberrations in tumors
and hereditary diseases.
Cancer etiology and development is associated with hereditary or acquired
genomic alterations. Among these, genomic imbalances play a prominent role
with deletions indicating the localization of tumor suppressor genes (e.g.
NF2, P53 or ATM) or amplifications frequently affecting protooncogenes (e.g.
MYC). Such aberrations may lead to an inactivation or, by a so-called “dosage
effect”, activation of genes relevant to the initiation and progression of tumor
cells. Genomic imbalances also play an important role in the field of clinical
genetics. Many human mental retardation syndromes, congenital malforma-
tions and miscarriages are caused by defined copy number gains or losses of
various chromosomal regions, whole chromosomes, or by small subtelomeric
chromosome rearrangements [1-5]. Besides the most frequent aneuploidies of
human chromosomes, such as Patau syndrome (trisomy of chromosome 13),
Edward syndrome (trisomy of chromosome 18) or Down syndrome (trisomy of
chromosome 21), a number of congenital diseases are associated with smaller
imbalances, mostly microdeletions: e.g. Prader-Willi syndrome (15q12), An-
gelman syndrome (15q12), Williams syndrome (7q11.2), or DiGeorge syn-
drome (22q11.21). Identification of chromosomal imbalances has significantly
contributed to the detection of genes playing a pathogenic role and the elucida-
tion of molecular mechanisms responsible for defined phenotypes in malignant
or congenital diseases.
Our current understanding of chromosomal alterations is mainly based on
chromosome banding analysis, visualization of targeted genomic regions by
fluorescence in situ hybridization (FISH) to metaphase chromosomes or inter-
phase cell nuclei, or traditional comparative genomic hybridization (CGH).
