Hos' (direct XyA DNA repeat) 7

Human Genetic Defects due to Retroposon Insertion

Since non-coding DNA vastly outnumbers coding DNA, it is hardly surprising that most insertions of transposable elements into the genome of higher organisms occurs in the non-coding regions. Nonetheless, occasional examples are known where insertion of a retrotransposon inactivates a gene so causing a hereditary defect. The first human case to be identified is a form of muscular dystrophy known as Fukuyama-type congenital muscular dystrophy (FCMD), that is particularly common in Japan although rare elsewhere. FCMD is one of the most common autosomal recessive disorders in Japan, occurring at a frequency of approximately 0.7-1.2 per 10,000 births, with a carrier frequency estimated to be as high as 1 in 80.

This condition is caused by the insertion of a retrotransposon, which is approximately 3,000 bases long into the 3'-untranslated region of the FCMD gene. This could theoretically result in an altered secondary structure for the FCMD mRNA, possibly rendering it unstable. In any case, little of no detectable mRNA is seen in affected cells. The FCMD gene codes for a 461-amino-acid protein that is normally expressed in brain, skeletal muscle, and heart and is involved in muscle function.

Genetic analysis indicates that the retrotransposon insertion in the FCMD gene could have been derived from a single ancestor who lived 2,000 to 2,500 years ago. This was about the time that the Yayoi people migrated to Japan from Korea and China, giving rise to the possibility, as yet unproven, that these immigrants brought the defective FCMD allele into the Japanese population. [It is thought that humans migrated from the Asian continent to Japan in two waves. The first wave brought hunter-gatherers of the Jomon culture over 10,000 years ago. The second wave brought the Yayoi people from the Korean Peninsula about 2,300 years ago. By around 300 AD the Yayoi had spread through most of Japan. The Yayoi brought metalworking, weaving and rice growing to Japan.]

Some retro elements are closely related to retroviruses.

Retroposons have only one or two genes and lack the ability to make virus particles and infect other cells. Nonetheless, retro-elements that are intermediate between retroposons and retroviruses do exist. Some retro-elements pack their RNA into defective virus-like particles. However, these particles are not released from the cell where they were assembled and therefore cannot infect other cells. These elements are sometimes called endogenous retroviruses. Defective versions of these, known as retrovirus-like elements, are common in animal cells where they often exist in multiple copies.

The highly repetitive sequences known as LINEs are related to retrotransposons.

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