What it means to have a mutation and what role mutations play in Huntington’s disease.
Is expansion more likely to come from the mother or the father?
A variety of studies have produced overwhelming evidence suggesting that expanded CAG repeat regions in the Huntington gene originate in the father more often than in the mother. The strongest evidence seems to come from studies of juvenile HD. Typically in HD, the longer the CAG repeat region in the Huntington gene, the earlier the person will start to experience the symptoms of the disease. For example, a person with 90 copies of CAG will likely start to experience the symptoms of HD earlier than a person with only 50 copies. If the person has enough CAGs, he or she may have juvenile HD and experience symptoms as early as childhood. (For a more in-depth discussion of juvenile HD, click here.) What the studies have found is that fatherly (paternal) transmission of juvenile HD is much more common than motherly (maternal) transmission. In many cases, if the juvenile HD arose from an expansion, researchers are able to prove that this expansion originated in the father. Thus, since juvenile HD often results from very long expansions and seems to arise more frequently from fatherly transmission, the studies provide sound evidence that expansion comes from the father. For more information on the inheritance of HD, click here.
Another research group performed a very interesting study on mice with HD. The study looked at the CAG repeat size in sons and daughters of the same father mouse. What the study found was that the sons predominately had an expanded number of CAGs (compared to the father), while the daughters had a contracted number (fewer CAGs than the father). These results are quite intriguing because, for the first time, they appear to imply that the gender of the baby has an effect on expansion. Because of this, the researchers suggested that, although the HD allele is known to reside on chromosome 4, there may also be X chromosome or Y chromosome factors at work in determining expansion. They also suggested that this gender dependence in the baby may explain why expansion occurs through the fatherly line. While this study is quite interesting, it must be noted that not only is it very new research, but it was also performed using mice, not humans. Thus, while it may present wonderful new breakthroughs, we cannot be sure of this until more research is done, especially research on humans.
Last Modified: 1-28-04
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