Etiology of chromosomal aberrations

Origin of aneuploidies and polyploidies (see question No. 34 – Abnormalities in chromosome number, their causes and clinical presentations in man)
Origin of structural aberrations:
- chromosome breaks and rearrangements during gamete formation (in meiosis) or in pre-gametic mitotic divisions of gonadal cells – resulting in stable products having one centromere and two telomeres
  - one centromere is necessary for regular segregation in mitosis (unstable dicentric chromosomes undergo secondary rearrangements)
  - telomeres maintain the integrity of the ends of linear chromosome structure (in deleted chromosomes new telomeres are added by **telomere synthesis or by mechanism of telomere capture)
- causes of spontaneous breaks – see below (external effects)

(= chromosome breaks and rearrangements during mitotic divisions of somatic cells)

External effects (physical, chemical, biological)

- random environmental factors – spontaneous breaks (UV light, ionizing radiation – cosmic rays, medical radiation (X-rays), drugs, viral infections)
- professional exposition (mutagens: chemicals – alkylating agents, intercalation substances...; radiation)
- oncological treatment (chemotherapy, radiotherapy)

Hereditary syndromes of chromosome instability

congenital defects of repair mechanisms - mostly double-strand DNA breaks repair
rare genetic disorders with AR inheritance, higher predisposition to cancer development
higher level of chromosome breaks and rearrangements detected in cytogenetic analysis
- ataxia teleangiectasia (defect of ATM gene - important for double-strand DNA breaks repair)
- xeroderma pigmentosum (defect of nucleotide excision repair)
- Bloom syndrome (extreme genome instability, high level of sister chromatid exchanges - SCEs, high frequency of mutations)
- Fanconi anemia
- Nijmegen breakage syndrome

Methods of analysis of acquired chromosomal aberrations (see question No. 31 – Methods of chromosomal examination)