Mechanisms of chromosome segregation errors in mammalian oocytes
von Eirini Bellou
Datum der mündl. Prüfung:2022-04-20
Betreuer:Dr. Melina Schuh
Gutachter:Prof. Dr. Timo Betz
Gutachter:Prof. Dr. Rüdiger Behr
Gutachter:Prof. Dr. Sarah Köster
Gutachter:Dr. Peter Lénárt
Gutachter:Dr. Ufuk Günesdogan
Diese Datei ist bis 19.04.2024 gesperrt.
EnglischDuring fertilization, a human embryo needs to inherit precisely one copy of each chromosome from both parents. However, human eggs frequently carry an incorrect number of chromosomes, they are aneuploid. Aneuploidy is the leading cause of aberrant embryonic development, resulting in miscarriages and genetic disorders such as Down syndrome. Early cytogenetic studies have shown that aneuploidy rates during meiosis differ for individual chromosomes. The reasons for variable aneuploidy rates are unknown. In this thesis, I used live-cell and super-resolution microscopy to investigate the behaviour of chromosomes with high and low aneuploidy rates in both human and porcine oocytes. In particular, I tested three different hypotheses for the origin of variable aneuploidy rates. First, I studied whether the precise architecture of the chromosomes affects their segregation behaviour. Second, I investigated whether chromosomes differ in how they interact with the microtubule spindle, the machinery which segregates the chromosomes during both meiosis I and meiosis II. Third, I investigated whether differences in chromosome cohesion biases subsets of chromosomes towards aneuploidy. Together, my results identify several reasons for the high aneuploidy rates of subsets of chromosomes, and reveal a new factor that contributes to chromosome-specific aneuploidy in meiosis.
Keywords: mammalian meiosis, chromosomes, acrocentric, metacentric; mammalian meiosis, chromosomes, acrocentric,