Robertsonian translocations between acrocentric chromosomes
Author: Sapient Fridge
Date: 19/10/07
Acrocentric chromosomes are those in which the centromere is located very near the end of thechromosome. During meiosis the location of the centromere makes acrocentric chromosomesvulnerable to Robertsonian translocations. This is where they fuse to anothernon-homologous acrocentric chromosome at or near their centromeres, resulting in a single long chromosome containing the genes from both of the originals.
Theremaining generic material which existed on the chromosomes beyond the centromere may fuse and remain in the cell but it will probably subsequently be lost during cell division (1) as the lack of a centromere makes it unlikely to be replicated properly during cell division (2).
The loss of the DNA from the short leg of an acrocentric chromosomes may not cause a problem due to the lack of geneslocated there. In the case of a metacentric chromosome, where the centromere is more central, it will almost certainly mean the loss of large numbers of vital genesresulting in a non-viable zygote.
An ancient example of Robertsonian translocation appears to be the fusing of two acrocentric chromosomes which existed in the common ancestor of the great apes and humans. The chromosomes appear to have fused to become chromosome 2 in humans(3) but the great apesstill have two acrocentric chromosomes in which the genes match the human chromosome 2 sequence (4).
A more common example of Robertsonian translocations is the fusing of chromosomes 14 and 21 which is one of the causes of Downs syndrome. A prospective parent may be a carrier of the problematic fused chromosome, yet show no symptoms. This is because although they have one chromosome less, they still have a full compliment of genes.
During mitosis the merged chromosome will duplicate itself without problem as will the normal 14 and 21 chromosomes. This means the daughter cells will still have the correct number of genes in total and will behave normally. The problem arises during meiosis as the resulting gametes may have too many or too few genes,which will affect the phenotype of the next generation.
During meiosis each chromosome matches up with its homologous partner in metaphase 1 to exchange chromosome sections via crossover. In the case of the fused chromosome there is no single homologous partner so it pairs with both the non-fused 14 and 21 chromosomes forming a trivalent (5). After telophase 1, two of the three chromosomes will end up in one cell and the remaining chromosome will end up in the other. The resulting distribution of genes will be unbalanced if one of the normal chromosomes ends up in the same cell as the fused chromosome.
If both normal chromosomes are successfully pulled to the opposite pole from the fused chromosome then two gametes will be normal and two will be carriers of the fused chromosome. Any offspring produced from carrier gametes will have a normal phenotype even though they have the fused chromosome.
If a normal chromosome ends up being pulled to the same pole as the fused chromosome atanaphase 1 then both of the two gametesproduced from that pole will end up with an extra copy of the genes that it contained. The two gametesproduced from the cellcontaining thegenetic material at the other pole which did not get the normal chromosomewillbe lacking the genes that it contained.
If chromosome 21 ends up being pulled to the same pole as the fused chromosome then the gametes will have two copies of the chromosome 21 genes, one normal set and one set from the fused chromosome. If one of these is fertilised with a normal gamete then the resulting zygote will have three copies of the chromosome 21 genes. This is known as trisomy 21 and the phenotype is Downs syndrome. The other combinations which result in monosomy 21, monosomy 14 and trisomy 14 are not viable and do not result in live births.
When two chromosomes merge like this it changes the inheritance pattern for the genes involved because the genes are now on the same chromosome whereas previously they were on separate chromosomes. Genes which are far apart on the new chromosome will still be subject to independent assortment because they can be separated during crossover,but the genes which are now close together on either side of the centromere will be more likely to be inherited as a single unit.
In the earlier example of the creation of chromosome 2 from the fusing of two chromosomes in the common ancestor of humans and great apes, the linking of genes could provide the explanation as to why the fused chromosome became ubiquitous in the population. If particular pairs of genes work well in combination then having them closer together on the chromosomes would mean that they were more likely to be passed on as one unit to the next generation. This could help a particularly advantageous combination spread through the population more rapidly, thus giving them an edge over rival populations in which the genes were not linked.
(1) Dummies guide to genetic P230-P231
(2) Essential genetics P166-P167
(3) Essential genetics P168
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