Chapters authored
What Causes Down Syndrome?
Trisomy 21 (Down Syndrome) is the model human phenotype for all genome gain-dosage imbalance situations, including microduplications. Years after the sequencing of chromosome 21, the discovery of functional genomics and the creation of multiple cellular and mouse models provided an unprecedented opportunity to demonstrate the molecular consequences of genome dosage imbalance. It was stated years ago that Down syndrome, caused by meiotic separation of chromosome 21 in humans, is associated with advanced maternal age, but defining and understanding other risk factors is insufficient. Commonly referred to as Down syndrome (DS) in humans, trisomy 21 is the most cited genetic cause of mental retardation. In about 95% of cases, the extra chromosome occurs as a result of meiotic non- nondisjunction (NDJ) or abnormal separation of chromosomes. In most of these cases the error occurs during maternal oogenesis, especially in meiosis I.
Part of the book: Down Syndrome and Other Chromosome Abnormalities
Mechanisms of Aneuploidy
Aneuploidy is a very common occurrence in humans and occurs in an estimated 20–40% of all pregnancies. It is the most prominent cause of miscarriages and congenital defects in humans and is the main obstacle to infertility treatment. The vast majority of aneuploidies are caused by maternal meiotic non-disjunction errors. High levels of recombination errors were observed in studies on fetal oocytes. This suggests that some oocytes are more prone to not being separated due to events occurring before birth. Cell cycle checkpoints that work in the meiotic phase and metaphase-anaphase transition work more moderately in women than in men. As a result, while there are abnormal cells that have been sorted out in spermatogenesis, in females these cells can escape the actual control and ultimately give rise to aneuploid eggs.
Part of the book: Down Syndrome and Other Chromosome Abnormalities