# Huntington's Disease - Math and Biology **URL:** \ **Category:** Factual Questions\ **Created:** [June 27, 2012, 7:55pm UTC](https://boards.straightdope.com/t/huntingtons-disease-math-and-biology/626498 "2012-06-27T19:55:01Z")\ **Posts on this page:** 17\ **Page:** 2
**Author:** ![IceQube](https://avatars.discourse-cdn.com/v4/letter/i/dfb087/32.png) [@IceQube](https://boards.straightdope.com/u/IceQube)\ **Post date:** [June 27, 2012, 10:54pm UTC](https://boards.straightdope.com/t/huntingtons-disease-math-and-biology/626498/21 "2012-06-27T22:54:30Z")
> [@Smeghead](#): > > As a grad student in biology, I would answer that the correct probability cannot be determined without more information. Implicit in your answer is the assumption that the two situations are equally likely. You simply cannot assume that. Your answer is not consistent with the idea that the frequencies are unknown; it is true ONLY if the frequencies are 50/50. Then I suppose the answer lies in whether the question writer expects me to consider frequencies. I doubt this is the case, but I’ll keep it in mind. More likely, however, given the question and its answer choices, is that the question writer wanted the test-taker to consider that HH and Hh are both possible genotypes for the “affected” person. Note that there is no option between 50% and 75%. ---
**Author:** ![Iggy](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/iggy/32/3364_2.png) [@Iggy](https://boards.straightdope.com/u/Iggy)\ **Post date:** [June 27, 2012, 10:58pm UTC](https://boards.straightdope.com/t/huntingtons-disease-math-and-biology/626498/22 "2012-06-27T22:58:47Z")
> [@IceQube](#): > > \*\*Let’s assume I wasn’t talking about Huntington’s here. \*\*I was just talking about some autosomal dominant disease. Because we do not know the specific autosomal dominant disease, we do not know the relative frequencies of the genotypes. > > And for this autosomal disease, we are told to cross an “affected” parent with an “unaffected” parent. We want to chance that the offspring will be affected. The answer choices are below. Which would you pick? > > a) 0% > b) 25% > c) 50% > d) 75% > \ Given that question I would hold my nose and answer c) 50%. Then I would remind myself that it was probably some English major who wrote the question. :rolleyes: ---
**Author:** ![lazybratsche](https://avatars.discourse-cdn.com/v4/letter/l/ba8739/32.png) [@lazybratsche](https://boards.straightdope.com/u/lazybratsche)\ **Post date:** [June 27, 2012, 11:06pm UTC](https://boards.straightdope.com/t/huntingtons-disease-math-and-biology/626498/23 "2012-06-27T23:06:49Z")
If the test is well-written, you won’t encounter a question that ambiguous. Though I can’t guarantee that the MCAT is well-written… and I bet you’re dealing with a lot of less-well-written test prep material right now. But you should be OK on this topic, you seem to have a good handle on the concept. Just be careful with your assumptions! ---
**Author:** ![IceQube](https://avatars.discourse-cdn.com/v4/letter/i/dfb087/32.png) [@IceQube](https://boards.straightdope.com/u/IceQube)\ **Post date:** [June 27, 2012, 11:08pm UTC](https://boards.straightdope.com/t/huntingtons-disease-math-and-biology/626498/24 "2012-06-27T23:08:42Z")
> [@lazybratsche](#): > > If the test is well-written, you won’t encounter a question that ambiguous. Though I can’t guarantee that the MCAT is well-written… and I bet you’re dealing with a lot of less-well-written test prep material right now. > > But you should be OK on this topic, you seem to have a good handle on the concept. Just be careful with your assumptions! I’ll be sure to read the question carefully and entertain all the possibilities on the actual MCAT. Thank you, and thank you all for helping me with the original question. I agree - it’s ambiguous, and could definitely be clarified. ---
**Author:** ![Chronos](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/chronos/32/134_2.png) [@Chronos](https://boards.straightdope.com/u/Chronos)\ **Post date:** [June 27, 2012, 11:41pm UTC](https://boards.straightdope.com/t/huntingtons-disease-math-and-biology/626498/25 "2012-06-27T23:41:30Z")
If the question didn’t specify, then I would assume that they’re testing whether the student has the judgment to know when to make a reasonable approximation and assume that the homozygous genotype is negligible. This is usually a good approximation. It would also be an approximation to say that the homozygous and heterozygous genotypes are equally common, but that would almost always be a terrible approximation. It’s like in physics problems: They almost never explicitly tell you to ignore air resistance and the curvature of the Earth, but you should almost always ignore them anyway. ---
**Author:** ![Smeghead](https://avatars.discourse-cdn.com/v4/letter/s/f1d935/32.png) [@Smeghead](https://boards.straightdope.com/u/Smeghead)\ **Post date:** [June 28, 2012, 12:01am UTC](https://boards.straightdope.com/t/huntingtons-disease-math-and-biology/626498/26 "2012-06-28T00:01:41Z")
> [@IceQube](#): > > Then I suppose the answer lies in whether the question writer expects me to consider frequencies. I doubt this is the case, but I’ll keep it in mind. But, see, that’s the point I’m trying to make. You’re making this assumption that treating it as 50/50 is as close as you can get to leaving that factor out completely; that the 50/50 option is the best approximation to “we don’t know”. It’s not. There IS no best approximation to “we don’t know”, and 50/50 is just as wrong as 95/5, 80/20, or 51/49. ---
**Author:** ![Hari\_Seldon](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/hari_seldon/32/5173_2.png) [@Hari\_Seldon](https://boards.straightdope.com/u/Hari_Seldon)\ **Post date:** [June 28, 2012, 1:25am UTC](https://boards.straightdope.com/t/huntingtons-disease-math-and-biology/626498/27 "2012-06-28T01:25:28Z")
Huntington’s is not a simple mendelian trait. Here is what wiki [Huntington's disease - Wikipedia](http://en.wikipedia.org/wiki/Huntington%27s_disease) has to say (in part): > [@](#): > > Genetics > > All humans have two copies of the Huntingtin gene (HTT), which codes for the protein Huntingtin (Htt). The gene is also called HD and IT15, which stands for ‘interesting transcript 15’. Part of this gene is a repeated section called a trinucleotide repeat, which varies in length between individuals and may change length between generations. When the length of this repeated section reaches a certain threshold, it produces an altered form of the protein, called mutant Huntingtin protein (mHtt). The differing functions of these proteins are the cause of pathological changes which in turn cause the disease symptoms. The Huntington’s disease mutation is genetically dominant and almost fully penetrant: mutation of either of a person’s HTT genes causes the disease. It is not inherited according to sex, but the length of the repeated section of the gene, and hence its severity can be influenced by the sex of the affected parent. The point is that it is caused by a repeated segment of a particular codon and the severity as well as age of onset is determined by the number of times it is repeated. Moreover, the number of repeats tends to increase in each generation, resulting in earlier onset (usually). The probability of a double dose being negligible, you can assume that the probability of inheritance is essentially 50%. I can’t give a cite offhand, but I once read that the disease has a measurable effect long before symptoms appear. ---
**Author:** ![Iggy](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/iggy/32/3364_2.png) [@Iggy](https://boards.straightdope.com/u/Iggy)\ **Post date:** [June 28, 2012, 1:42am UTC](https://boards.straightdope.com/t/huntingtons-disease-math-and-biology/626498/28 "2012-06-28T01:42:49Z")
> [@Hari\_Seldon](#): > > Huntington’s is not a simple mendelian trait. Here is what wiki > [Huntington's disease - Wikipedia](http://en.wikipedia.org/wiki/Huntington%27s_disease) has to say (in part): > > The point is that it is caused by a repeated segment of a particular codon and the severity as well as age of onset is determined by the number of times it is repeated. Moreover, the number of repeats tends to increase in each generation, resulting in earlier onset (usually). The probability of a double dose being negligible, you can assume that the probability of inheritance is essentially 50%. I can’t give a cite offhand, but I once read that the disease has a measurable effect long before symptoms appear. Huntingtons is a Mendalian trait. It is a single gene disorder, and assortment is independent with equal expression whether maternally or paternally derived. Yes the Huntingtons gene has a codon repeat. That does not change the frequency of assortment of the allele. It may affect the penetrance of the trait but that is a different matter. ---
**Author:** ![ultrafilter](https://avatars.discourse-cdn.com/v4/letter/u/3d9bf3/32.png) [@ultrafilter](https://boards.straightdope.com/u/ultrafilter)\ **Post date:** [June 28, 2012, 2:38am UTC](https://boards.straightdope.com/t/huntingtons-disease-math-and-biology/626498/29 "2012-06-28T02:38:38Z")
> [@Smeghead](#): > > But, see, that’s the point I’m trying to make. You’re making this assumption that treating it as 50/50 is as close as you can get to leaving that factor out completely; that the 50/50 option is the best approximation to “we don’t know”. It’s not. There IS no best approximation to “we don’t know”, and 50/50 is just as wrong as 95/5, 80/20, or 51/49. I’m not going to claim that it’s appropriate here (or ever), but there is [an intellectual tradition](http://en.wikipedia.org/wiki/Principle_of_indifference) of assigning equal probabilities to different outcomes when nothing is known. ---
**Author:** ![Harmonix](https://avatars.discourse-cdn.com/v4/letter/h/3ec8ea/32.png) [@Harmonix](https://boards.straightdope.com/u/Harmonix)\ **Post date:** [June 28, 2012, 7:54am UTC](https://boards.straightdope.com/t/huntingtons-disease-math-and-biology/626498/30 "2012-06-28T07:54:03Z")
> [@Iggy](#): > > Huntingtons is a Mendalian trait. It is a single gene disorder, and assortment is independent with equal expression whether maternally or paternally derived. > > Yes the Huntingtons gene has a codon repeat. That does not change the frequency of assortment of the allele. It may affect the penetrance of the trait but that is a different matter. I would argue that the disease is Mendelian, but not _ **simple** _ Mendelian. However, I will note that HTT Is listed in OMIM database (Online Mendelian Inheritance in Man:An Online Catalog of Human Genes and Genetic Disorders) to OP: I would pick 50%. The question is bad, and I would report it after the test to the test-maker. There are procedures for that I believe. ---
**Author:** ![cjepson](https://avatars.discourse-cdn.com/v4/letter/c/a9adbd/32.png) [@cjepson](https://boards.straightdope.com/u/cjepson)\ **Post date:** [June 28, 2012, 4:08pm UTC](https://boards.straightdope.com/t/huntingtons-disease-math-and-biology/626498/31 "2012-06-28T16:08:15Z")
> [@ultrafilter](#): > > I’m not going to claim that it’s appropriate here (or ever), but there is [an intellectual tradition](http://en.wikipedia.org/wiki/Principle_of_indifference) of assigning equal probabilities to different outcomes when nothing is known. But then the question becomes, what are the “outcomes” to which equal probabilities are being assigned. The example appears to define the outcomes that have equal probabilities as the two genotypes “GG” and “Gg”. Actually, however, these are three outcomes – GG, Gg, and gG. If we assume that the probability of being GG is equal to the combined probabilities of being either Gg or gG, then the corollary is that we are assuming that the frequency of the G allele in the population of “affected” individuals is 80%. That is: For every 2 affected individuals who are heterozygous (Gg or gG), there are two affected individuals who are homozygous (GG and GG). So there are a total of six G alleles and two g alleles, or 80% G. Given our state of ignorance, I think it would be much more reasonable to assume that the G and g alleles have equal probability in the **overall** population (not just the population of affected individuals). In this case, among affected individuals, we should expect twice as many heterozygotes (Gg or gG) as homozygotes (GG). So the “correct” answer would be 66.7%, and all the given response options are wrong. ---
**Author:** ![Chronos](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/chronos/32/134_2.png) [@Chronos](https://boards.straightdope.com/u/Chronos)\ **Post date:** [June 28, 2012, 4:20pm UTC](https://boards.straightdope.com/t/huntingtons-disease-math-and-biology/626498/32 "2012-06-28T16:20:25Z")
And besides, this isn’t a situation where nothing is known. Even if we don’t know any of the statistics for Huntington’s Disease specifically, we do know from the statement of the question that it’s a disease resulting from a dominant gene. That tells us quite a lot: It’s very easy to select against a dominant trait, and thus all dominant genetic diseases are quite rare. ---
**Author:** ![IceQube](https://avatars.discourse-cdn.com/v4/letter/i/dfb087/32.png) [@IceQube](https://boards.straightdope.com/u/IceQube)\ **Post date:** [June 28, 2012, 6:00pm UTC](https://boards.straightdope.com/t/huntingtons-disease-math-and-biology/626498/33 "2012-06-28T18:00:18Z")
> [@cjepson](#): > > Actually, however, these are three outcomes – GG, Gg, and gG. Wait. Gg and gG are different? ---
**Author:** ![ultrafilter](https://avatars.discourse-cdn.com/v4/letter/u/3d9bf3/32.png) [@ultrafilter](https://boards.straightdope.com/u/ultrafilter)\ **Post date:** [June 28, 2012, 6:28pm UTC](https://boards.straightdope.com/t/huntingtons-disease-math-and-biology/626498/34 "2012-06-28T18:28:36Z")
> [@IceQube](#): > > Wait. Gg and gG are different? From the standpoint of probability, not genetics. ---
**Author:** ![cjepson](https://avatars.discourse-cdn.com/v4/letter/c/a9adbd/32.png) [@cjepson](https://boards.straightdope.com/u/cjepson)\ **Post date:** [June 28, 2012, 6:34pm UTC](https://boards.straightdope.com/t/huntingtons-disease-math-and-biology/626498/35 "2012-06-28T18:34:49Z")
> [@IceQube](#): > > Wait. Gg and gG are different? Well, they are separate outcomes. It’s like flipping a coin twice. There’s one way of getting two heads (HH), one way of getting two tails (TT), and two ways of getting a head and a tail (HT and TH). Similarly, there’s one way of being homozygous-normal (gg), one way of being homozygous-affected (GG), and two ways of being heterozygous (Gg and gG). So if the two alleles are equally prevalent in a population, the number of homozygotes of either type will be half the number of heterozygotes. This follows from the [Hardy-Weinberg principle](hardy-weinberg principle wiki). ---
**Author:** ![IceQube](https://avatars.discourse-cdn.com/v4/letter/i/dfb087/32.png) [@IceQube](https://boards.straightdope.com/u/IceQube)\ **Post date:** [June 28, 2012, 6:43pm UTC](https://boards.straightdope.com/t/huntingtons-disease-math-and-biology/626498/36 "2012-06-28T18:43:39Z")
I think if I got anything out of this discussion it is that the question is poorly written. I’ll have to lucubrate over the probability tangent later … ---
**Author:** ![PastTense](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/pasttense/32/14550_2.png) [@PastTense](https://boards.straightdope.com/u/PastTense)\ **Post date:** [January 17, 2025, 9:32pm UTC](https://boards.straightdope.com/t/huntingtons-disease-math-and-biology/626498/37 "2025-01-17T21:32:19Z")
Some new research out: > The mutation in the huntingtin (HTT) gene, which causes the incurable, dominantly inherited Huntington’s disease, was identified decades ago, following one of the most closely watched disease gene quests in the early years of gene mapping. But exactly how this triplet repeat expansion mutation functions to cause the disease has eluded researchers—until now. > > A team of researchers from the Broad Institute, Harvard Medical School, and McLean Hospital have identified at last how the mutation causes symptom development later in life, opening doors to therapeutic approaches for delaying or preventing development of the disease. > **[Groundbreaking Huntington Study Reveals Somatic DNA-Repeat Expansion](https://www.genengnews.com/topics/translational-medicine/groundbreaking-huntington-study-reveals-somatic-dna-repeat-expansion/)** > > How the mutation in the huntingtin gene functions to cause the disease has eluded researchers—until now. The original open access article: [https://www.cell.com/cell/fulltext/S0092-8674(24)01379-5](https://www.cell.com/cell/fulltext/S0092-8674(24)01379-5) [Previous page](https://boards.straightdope.com/t/huntingtons-disease-math-and-biology/626498.md?page=1)