Etiology of chromosomal aberrations

Chromosomal aberrations

 * 1) Abnormalities in chromosome number
 * 2) aneuploidy
 * 3) *monosomy
 * 4) *trisomy (or tetrasomy, pentasomy...)
 * 5) polyploidy
 * 6) *triploidy
 * 7) *tetraploidy,...
 * 8) Abnormalities in chromosome structure
 * 9) balanced
 * 10) *translocation
 * 11) *inversion
 * 12) *insertion
 * 13) unbalanced
 * 14) *deletion (incl. ring chromosome)
 * 15) *duplication
 * 16) *isochromosome

Etiology of congenital 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)

Etiology of acquired chromosomal aberrations
(= 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)