CHROMOSOMAL ANDGENE ABERRATION(Duplication, Deletion, Inversion, Translocation) ENDAYA, DANICA FAYE M. MANGOSING VIDA FAYE S.
IntroductionCongenital abnormalities can be caused by ananomaly in the number or structure of thechromosomes. Disorders in thegametogenesis, that is, in the first and secondmeiotic divisions in the formation of oocytesand sperm cells, lead to such defects.
Staining methodChromosomal mutations can bemade visible with staining methods(banding techniques). Followingthe staining the chromosomes areanalyzed using a 1000xenlargement. With this one canrecognize the chromosomes asstriped cords and display them in akaryogram, after they have beenordered according to their size andthe positions of the centromeres.Various groups of similarchromosomes are created in this
Today, small aberrations are examined using amolecular cytogenetic (FISH) approach.Among other things, the FISH (fluorescence-in-situ-hybridizing) method makes possible thetargeted identification of partial aneuploidiessuch as deletions, duplications and unbalancedtranslocations (see below) that cannot beresolved with a light microscope. A comprehensive array of DNA probes andtechniques are today available from which onecan choose for utilization, depending on thediagnostic problem being worked on. With theFISH method chromosomal alterations can beanalyzed down to a size of ca. 5 millionnucleotides
Structural aberrations are the result ofchromosomal breaks that occur duringmeiosis. deletion, duplication isochromosome formation lead to an abnormal phenotype.while; insertion inversion translocation can be balanced. This means that the carrier of this structural chromosome aberration can escape notice phenotypically, because the entire genetic material is present.
Deletion A deletion can happen in every chromosome and exhibit every size. The consequences of a deletion depends on the size of the missing segment and which genes are found on it.
Cri du Chat syndrome A partial deletion on the short arm (p) of chromosome 5 is responsible for the “cri du chat" syndrome The "cri du chat" syndrome manifests itself through cat-like crying of the newborn. This disorder is accompanied by microcephaly, severe psychosomatic and mental retardation and cardiac defects.
Duplication A chromosome duplication is the doubling of a chromosome piece. A duplication is sometimes termed a "partial trisomy". If, therefore, a duplication is present, the person is equipped with 3 copies of the genes in the associated chromosome segment. This means that extra directions (genes) are present, leading to congenital abnormalities or developmental problems.
Fragile X syndrome The fragile X syndrome results from multiple duplications of a CGG segment (trinucleotide) in the 5 untranslated region of the FMR1 gene on the X chromosome (Xq27). Since it is an X linked mutation men are more affected than women. The fragile X syndrome leads to one of the most frequent forms of inherited mental retardation. In addition, the syndrome causes a prognathism, the face is long and small and the patient has large
Inversion If chromosome pieces that have been broken out become inserted again, but reversed, an inversion has occurred. The phenotype of this disorder is usually unobtrusive, since the entire chromosomal information is still present.
When the interchanged region includes the centromere, one refers to it as a pericentric inversion,
Insertion If chromosome pieces are reinserted somewhere else, this is referred to as an insertion. Carriers of such insertions can be phenotypically inconspicuous because no information has been lost.
Isochromosomiebildung Isochromosome formation is a relatively frequent chromosomal aberration, mainly in X chromosomes. Here the chromosomes are not divided along their length (see the normal division of the chromosomes figure) but transversely. The resulting isochromosomes (karyogram) either have two short or two long arms. Persons with this X chromosome anomaly have the same phenotype as patients suffering from Turners syndrome (45, X0). This is explained by the fact that a X chromosome arm is missing.
Normal division Isochromosome formationof thechromosome
Reciprocal translocation In a reciprocal translocation two broken off chromosome pieces of non- homologous chromosomes are exchanged. This is a relatively frequent anomaly. One finds it with an incidence of 1:500 newborns.
Reciprocal translocations are frequently balanced because the entire genetic material is present. Problems occur, though, in gamete formation.
Cancer and TumorsToday it is known that balancedtranslocations can also lead topathogenic disorders in that proto-oncogenes, which as normalgenes in their customaryenvironment are frequentlyresponsible for the controlling cellproliferation, can be transformedinto oncogenes throughtranslocation events. They arethe cause for the origin of manytumors and types of cancerbecause in other environments theyachieve totally different effects.
Robertsonian translocation Another frequently observed anomaly (1:1000 newborns) is the robertsonian translocation, which occurs between two acrocentric chromosomes of groups G and D. It is also referred to as the centric fusion of two acrocentric chromosomes.
Carriers of such robertsonian translocations are phenotypically inconspicuous. Also here, though, problems arise when it comes to gamete formation because, normally, the diploid chromosome set is halved thereby.