Aneuploidy in eggs is a leading cause of miscarriages or viable developmental syndromes. Aneuploidy rates differ between individual chromosomes. For instance, chromosome 21 frequently missegregates, resulting in Down Syndrome. What causes chromosome-specific aneuploidy in meiosis is unclear. Chromosome 21 belongs to the class of acrocentric chromosomes, whose centromeres are located close to the chromosome end, resulting in one long and one short chromosome arm. We demonstrate that acrocentric chromosomes are generally more often aneuploid than metacentric chromosomes in porcine eggs. Kinetochores of acrocentric chromosomes are often partially covered by the short chromosome arm during meiosis I in human and porcine oocytes and orient less efficiently toward the spindle poles. These partially covered kinetochores are more likely to be incorrectly attached to the spindle. Additionally, sister chromatids of acrocentric chromosomes are held together by lower levels of cohesin, making them more vulnerable to age-dependent cohesin loss. Chromosome architecture and low cohesion therefore bias acrocentric chromosomes toward aneuploidy during mammalian meiosis.
Aneuploidy in eggs is a leading cause of miscarriages or viable developmental syndromes. Aneuploidy rates differ between individual chromosomes. For instance, chromosome 21 frequently missegregates, resulting in Down Syndrome.
Purpose: Although chromosome 21 is the smallest human chromosome, it is highly relevant in the pathogenicity of both cancer and congenital diseases, including Alzheimer disease and trisomy 21 (Down syndrome). In addition, cases with rare structural variants (SVs) of chromosome 21 have been reported. These events vary in size and include large chromosomal events, such as ring chromosomes and small partial aneuploidies.
Jumping translocations (JT), linked to disease progression in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), involve the movement of a tri-tetra-somic 1q chromosome to various other chromosomes.
Research showed that in patients with SRSF2 mutations, JT was associated with changes in DNA methylation during treatment with 5'-azacytidine (AZA), revealing significant shifts in the methylome and impacting various biological pathways.
The study highlighted that epigenetic modifications, including changes in DNA methylation and specific signaling pathways like PI3K/AKT and MAPK, play a crucial role in the progression of myeloid neoplasms associated with
Laboratory of Genome Evolution, Department of Biology and Biotechnology Charles Darwin, Sapienza University of Rome, 00185 Rome, Italy. Electronic address:
- The text discusses how secondary structures, which are unique arrangements of nucleic acids caused by internal interactions, can occur in both RNA and single-stranded DNA, impacting key processes like DNA replication and transcription, thus affecting genome stability.
- The study focuses on the comparison of secondary structures in linear single-stranded DNA from different specialized human loci, such as centromeres and coding regions, revealing that centromeres have the highest complexity and instability in their secondary structures.
- Findings indicate that the intricate self-hybridizing properties of centromeric repeats may lead to chromosome missegregation when chromatin is disrupted, highlighting the functional importance of these structures in various DNA processes like transcription and recombination.
