From Principles of Life by H. Craig Heller, David E. Sadava, Mary V. Price:

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From what I understand, Huntington's disease exhibits varying degrees of penetrance depending on how many times the mutation is found in the person's genome. Penetrance is nearly complete if the incorrect base pair sequence is found over a certain number of times.

My question is what affects penetrance? Is it exclusively environmental?


closed as unclear what you're asking by fileunderwater, MattDMo, WYSIWYG, Chris, Bez Mar 3 '15 at 17:27

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    $\begingroup$ and your question is? $\endgroup$ – MattDMo Oct 30 '14 at 20:58
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    $\begingroup$ I also don't understand your question. That definition of penetrance says nothing about the environment. $\endgroup$ – canadianer Oct 30 '14 at 23:00
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    $\begingroup$ To me, it seems like you are arguing against the "exclusively environmental" idea in the section on Huntingtons. What makes you think/ask that it is exclusively environmental? The short answer to the title Q is No - the genetic background (genes at other loci) can for instance affect penetrance. You should also include a reference to the book you've scanned. $\endgroup$ – fileunderwater Oct 30 '14 at 23:30
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    $\begingroup$ @WYSIWYG - ~10% of patients have onset in their childhood (as young as 2) and teens. The majority develop their obvious symptoms in their 30's and 40's (some believe the earlier symptoms are largely overlooked) and only 10% develop the disease after 55. If you had the mutation, I doubt you would call it late onset. $\endgroup$ – anongoodnurse Oct 31 '14 at 7:01
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    $\begingroup$ @WYSIWYG - it is considered adult onset. As to percent of juvenile onset, see here, here and here. $\endgroup$ – anongoodnurse Oct 31 '14 at 9:20

Penetrance describes the frequency of a gene's expression:

Penetrance refers to the proportion of people with a particular genetic change (such as a mutation in a specific gene) who exhibit signs and symptoms of a genetic disorder. (Genetics Home Reference nih.gov)

More specifically:

[P]enetrance is defined as the percentage of individuals with a given genotype who exhibit the phenotype associated with that genotype. For example, an organism may have a particular genotype but may not express the corresponding phenotype, because of modifiers, epistatic genes, or suppressors in the rest of the genome or because of a modifying effect of the environment.

Note that the environment is only one factor affecting the expression of an allele.

Retinoblastoma and achondroplasia are often referred to in discussions about penetrance.

Retinoblastoma is caused by mutations in the Rb gene. Not all people who carry this mutation suffer from retinoblastoma (about 90% do). There are numerous inherited diseases (including cancers) in which the same mutation is not expressed in all the individuals who carry it. Achondroplasia, on the other hand, has 100% penetrance: every person with the specific point mutation in the fibroblast growth factor receptor 3 gene always has abnormal bone growth and dwarfism.

Huntingtons is a little different in that patients with 36 to 41 HD CAG repeats exhibit reduced penetrance; that is, some may not develop HD in their lifetime; however 100% of those with the mutation produce the abnormal/polyQ/polyglutamine-enlarged huntingtin. The age of onset is dependent on number of repeats but is affected by other modifiers (both genetic and environmental); this becomes less obvious in individuals with higher repeats sizes (e.g. greater than 44).

Huntington's is not a genotype affected only by environment.

Genetics in Medicine
A new model for prediction of the age of onset and penetrance for Huntington’s disease based on CAG length

  • $\begingroup$ however 100% of those with the mutation produce huntingtin.: Everyone produces huntingtin however its exact function is unknown. HD patients produce the Polyglutamine expanded one. $\endgroup$ – WYSIWYG Oct 31 '14 at 5:53

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