Human chromosomes: Structural and functional aspects

Abstract

Understanding the structural and molecular basis of the mitotic chromosome remains a basic challenge in cell biology and cytogenetics. The chromosomal behavior during cell division was first described in 1882. At the beginning of the last century, the chromosome theory of inheritance combined the cytological observations with the principles of Mendelian inheritance deduced from breeding experiments. This fundamental theory explained for the first time that the chromosomes are the units of heredity which are arrayed linearly on chromosomes as well as genetic linkage, chromosomal recombination, and the independent assortment of alleles localized on different chromosomes. The chromosome theory of inheritance was the prerequisite for the important improvements in the fields of experimental and clinical cytogenetics. After the definition of the exact number of human chromosomes 2n = 46 in 1955, it was demonstrated that different human aneuploidies are the leading cause of fetal loss, birth defects, and mental retardation and that duplications or deletions of even smaller chromosomal segments have profound consequences on normal gene expression, resulting in severe developmental and physiologic abnormalities. In the 1980s and 1990s, the field of conventional cytogenetics was revolutionized by the introduction of molecular cytogenetic techniques resulting in the recognition of the importance of subtle cytogenetic aberrations, such as microdeletions and microduplications.