History
The first record of a case of probable dengue fever is in a Chinese medical encyclopedia from the Jin Dynasty (266–420) which referred to a "water poison" associated with flying insects. The primary vector, A. aegypti, spread out of Africa in the 15th to 19th centuries due in part to increased globalization secondary to the slave trade. There have been descriptions of epidemics in the 17th century, but the most plausible early reports of dengue epidemics are from 1779 and 1780, when an epidemic swept across Southeast Asia, Africa and North America. From that time until 1940, epidemics were infrequent.In 1906, transmission by the Aedes mosquitos was confirmed, and in 1907 dengue was the second disease (after yellow fever) that was shown to be caused by a virus. Further investigations by John Burton Cleland and Joseph Franklin Siler completed the basic understanding of dengue transmission.The marked spread of dengue during and after the Second World War has been attributed to ecologic disruption. The same trends also led to the spread of different serotypes of the disease to new areas and the emergence of dengue hemorrhagic fever. This severe form of the disease was first reported in the Philippines in 1953; by the 1970s, it had become a major cause of child mortality and had emerged in the Pacific and the Americas. Dengue hemorrhagic fever and dengue shock syndrome were first noted in Central and South America in 1981, as DENV-2 was contracted by people who had previously been infected with DENV-1 several years earlier.
A parent with 35 repeats would be considered normal and would not exhibit any symptoms of the disease. However, that parents offspring would be at an increased risk of developing Huntingtons compared to the general population, as it would take only the addition of one more CAG codon to cause the production of mHTT (mutant HTT), the protein responsible for disease. Huntingtons very rarely occurs spontaneously; it is almost always the result of inheriting the defective gene from an affected parent. However, sporadic cases of Huntingtons in individuals who have no history of the disease in their families do occur. Among these sporadic cases, there is a higher frequency of individuals with a parent who already has a significant number of CAG repeats in their HTT gene, especially those whose repeats approach the number (36) required for the disease to manifest. Each successive generation in a Huntingtons-affected family may add additional CAG repeats, and the higher the number of repeats, the more severe the disease and the earlier its onset. As a result, families that have had Huntingtons for many generations show an earlier age of disease onset and faster disease progression. Non-trinucleotide expansions
The majority of diseases caused by expansions of simple DNA repeats involve trinucleotide repeats, but tetra-, penta- and dodecanucleotide repeat expansions are also known that cause disease. For any specific hereditary disorder, only one repeat expands in a particular gene. Mechanism
Triplet expansion is caused by slippage during DNA replication or during DNA repair synthesis.