Human Cytogenetics: from Classical to Molecular Karyotyping

The establishment of human diploid chromosome number (Tjio and Levan, 1956), have led to the foundations of human cytogenetics. Since then, due to the rapid developments of new techniques for chromosome analysis, many other chromosome disorders were recognized. The introduction of banding techniques, yielding a highly reproducible banding pattern, allowed the reliable identification of every single chromosome and the precise diagnosis of structural and numerical chromosome aberrations. For more then 20 years, chromosome banding analysis has been the laboratory standard to identify structural and numerical chromosome abnormalities in preand postnatal cytogenetics as well as in cancer diagnosis. The resolution of classical cytogenetic techniques is limited to at best 4-5Mb and smaller chromosomal aberrations like small marker chromosomes, subtle translocations or complex chromosomal rearrangements often remain hidden. These diagnostic problems has been overcame to some degree, by the introduction of modern molecular cytogenetic techniques, like fluorescence in situ hybridization (FISH). The application of Comparative genomic hybridization (CGH) and microarray CGH has extended from screening for submicroscopic chromosomal imbalance in cancer cytogenetics to the detection of any type of gain or loss (resolution of 10-100 kb) of genetic material in dysmorphic and mentally retarded individuals with a normal conventional karyotype. To date around 20 000 chromosomal aberrations have been registered, and thay account for a large proportion of early spontaneous abortions, childhood disability and malignancy, as a consequence of somatic chromosome abnormalities. Current estimates show that 0.5-1.0% newborn infants will have a chromosome rearrangements recognizable either by conventional cytogenetics or by molecular cytogenetic method