Week 20 of SIP: Last Posting

Name: Hardina Bte Hamzah
Topic: Cytogenetics

Structural Abnormalities of Chromosomes

When chromosomes have replicated and are waiting to be separated into 2 daughter cells, chromosome breakage is frequently accompanied by exchange material from one chromatid to another. The exchange of material occurs during the pachytene period of the first meiotic division and is a mechanism built into the reproductive cycle to ensure the mixing of the gene pool. The exchange is called crossing over and it occurs when paired homologs form chiasmata. The abnormailties occur when the chromosomes break at non-homologous sites leading to unequal exchanges. 2 major classes of detectable rearrangements are rearrangements within a single chromosome and rearrangements involving more than 1 chromosome.

Examples of rearrangements within a single chromosome:

Deletion is a loss of chromosomal material. An interstitial deletion can arise from unequal crossing over at meiosis. Breaks can occur in 2 homologs at slightly different positions on the chromosomes and the pieces can be reconnected to the alternate chromosome. One chromosome could lose material while the other could gain material. This kind of mechanism is more likely to occur. Cri-du-chat syndrome is one of the examples of syndromes resulting from deletion.

Duplication occurs when a portion of one homolog may be present in duplicate. A duplicated segment may be inserted in the same order as the original segment. However, we cannot identify which piece was original. It can also become reversed. Duplication in the same order which also can be known as tandem duplication may probably results from unequal crossing over in meiosis or from a rearrangement between 2 chromatids during mitosis. Any duplication represents a trisomic state for whatever gene loci are present on the affected segment.

Inversion is a two-break structural irregularity that affects a single chromosome. The segment between the 2 breaks rotates 180 degrees and reattaches to the points of breakage. There are 2 types of inversion: Paracentric and Pericentric. In paracentric inversions, the centromere is not included in inverted segment and the arm ratio of the chromosome remains the same. In pericentric inversions, the inverted portion does include the centromere and the arm ratio may be changed.

Examples of rearrangements involving more than 1 chromosome:

Translocation is an exchange of genetic material between 2 or more non-homologous chromosomes. It is an abnormal mechanism but it can occur when 2 or more chromosomes break at the same time. Broken chromosome ends are regarded as sticky and can attract the cellular enzymatic repair service. Usually broken ends stay close to each other and are reunited. However, it is possible to mismatch the broken ends. The carrier of a balanced translocation may pass on the only part of the translocation which can result in genetically unbalanced offspring.

Dicentric chromosome possesses 2 centromeres and it is a result of the joining of homologous chromatids to form an isochromosome. An isochromosome is a chromosome in which the arms n either side of the centromere are morphologically identical ad bear the same gene loci. Dicentrics may cause problems during cell division, however, if the 2 centromeres are far apart on the derivative chromosome. If both centromeres are active, they can be drawn to opposite poles of the spindle resulting in formation of an anaphase bridge. Anaphase bridge is a chromosome that makes a bridge between 2 daughter cells at anaphase. When this happens, the dicentric can be left outside both daughter nuclei as they form or can break apart and cause loss or gain of chromosomal material.

Insertion is an addition of genetic material between 2 normally adjacent sections of a chromosome. The additional material could be a duplication of a section of the same chromosome but is more likely to come from a different chromosome. Insertions are difficult to identify unless there is a complementary deletion in the cell.