Cytogenetics and the evolution of medical genetics

Interest in cytogenetics may be traced to the development of the chromosomal theory of inheritance that emerged from efforts to provide the basis for Darwin's theory "On the origin of species by means of natural selection." Despite their fundamental place in biology, chromosomes and genetics had little impact on medical practice until the 1960s. The discovery that a chromosomal defect caused Down syndrome was the spark responsible for the emergence of medical genetics as a clinical discipline. Prenatal diagnosis of trisomies, biochemical disorders, and neural tube defects became possible and hence the proliferation of genetic counseling clinics. Maternal serum screening for neural tube defects and Down syndrome followed, taking the new discipline into social medicine. Safe amniocentesis needed ultrasound, and ultrasound soon found other applications in obstetrics, including scanning for fetal malformations. Progress in medical genetics demanded a gene map, and cytogeneticists initiated the mapping workshops that led to the human genome project and the complete sequence of the human genome. As a result, conventional karyotyping has been augmented by molecular cytogenetics, and molecular karyotyping has been achieved by microarrays. Genetic diagnosis at the level of the DNA sequence is with us at last. It has been a remarkable journey from disease phenotype to karyotype to genotype, and it has taken <50 years. Our mission now is to ensure that the recent advances such as prenatal screening, microarrays, and noninvasive prenatal diagnosis are available to our patients. History shows that it is by increased use that costs are reduced and better methods discovered. Chromosome research has been behind the major advances in our field, and it will continue to be the key to future progress, not least in our appreciation of chromosomal variation and its importance as a mechanism in Darwinian evolution.