Talk:Heterozygote advantage

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Moved from heterozygous advantage (~700 hits) to heterozygote advantage (~9000) as it's a the common form according to Google, and also from many textbooks such as Hartl & Clark Population Genetics (1998). --Lexor|Talk 10:31, Jan 24, 2005 (UTC)

Cystic fibrosis: The high incidence of CF genes in European populations is probably not due to cholera alone, but to diarrheal infections in general. So why is it much more common in people of European descent than in other populations? Because the CF gene is associated with salty sweat. In hot climates, the advantage of protection from diarrheal infection is less than the disadvantage of dehydration. Only in colder climates does the balance tilt towards an advantage for the CF gene. See Selective Advantages of the Mutant CFTR Gene

My edits and some suggestions

The original author of the section on Kalmus's paper (1945) probably understood the concept, but did not use the scientific vocabulary correctly. I have rewritten this section.

Perhaps there should be just one section devoted to examples from human genetics. Sickle cell anemia is clearly the classic example of heterozygote advantage in humans. I didn't touch the cystic fibrosis section. I haven't done much reading on that disease, but I can see from the comments here that it is incomplete and has inaccuracies. I feel we should cut it back to a summary paragraph, and use the "main article" approach, as I have done with Tay-Sachs disease.

A good addition to this article would be a discussion of hybrid corn. Can anybody take a picture of workers detasseling corn to contribute here? I know there are other examples of hybridization in agriculture. This one is interesting because a major industry is built around it. I may be exagerating its importance worldwide, since I live in Illinois and grew up in Wisconsin (where I worked for a few weeks one summer in high school detasseling corn). Also, researchers in corn genetics now downplay the benefits due to overdominance. Many believe that dominance alone may explain the superior yields of hybrid corn.

--Metzenberg 09:43, 17 August 2006 (UTC)

Omit Tay-Sachs. That theory really seems to be dead now. --Metzenberg 09:59, 13 May 2007 (UTC)

Estimating relative fitness, population genetics methods etc.

Assuming random mating and fitness differential is not due to fertility but chance of survival:

Gentotype AA Aa aa

Fitness 1-s 1 1-t

Selection in favor of the heterozygote(Aa) causes deviation from the hardy-weighberg equalibrium(p^2:2pq:q^2) and the relative geneotype freq. among adults...

p^2(1-s) : 2pq : q^2(1-t)

Freq. of AA = (1-s)/1

Freq. of Aa = 1

Freq. of aa = (1-t)/1

...Someone please expand on this and add it in.(I'm not really the person to do it). See Ridley(2004) page 126 for pop.gen. methods. Also there is lots of data on SCA (see Bodmer & Cavalli-Sforza 1976). I'll try to check back later to see if anyone has expanded on this, if not i'm going to just add what I know in a half assed fashion =) --Mike Spenard 04:08, 19 October 2006 (UTC)

Merge proposal

I have had a look at these two articles and the way overdominance currently is defined, it indeed belongs here. Problem is, the definition of overdominance is wrong! The two terms do NOT mean the same thing. Overdominance is the phenomenon where the heterozygote lies outside the range of both homozygotes. This is regardless of fitness. An example of overdominance would be AA=10, aa=5, and then Aa either >10 or <5. Heterozygote advantage could very well occur in a situation where Aa would be 7.5, but where this intermediate phenotypical value would be fitter than either homozygous parent. Both articles need to be rewritten to reflect this situation, I think, not merged. --Crusio (talk) 10:55, 5 August 2008 (UTC)

• Overdominance should be renamed, "Dominance versus overdominance". Originally, the article was called "overdominance hypothesis," but its title was shortened at some point, or some other merger was made. The article should not be about heterozygote advantage (one form of which is overdominance), but rather, about the evolving controversy between two competing theories (dominance and overdominance) that has persisted for about more than a century. By merging that article into heterozygote advantage, material on the dominance hypothesis gets eliminated. In fact, the dominance hypothesis seems to have trumped the overdominance hypothesis as an explanation for hybrid vigor, at least in plant genetics. The persistence of this controversy for a century and its development over time is an article topic that should not be merged into one of the two theories. I will create it as a new article, and then I have to agree that we should merge the other. Metzenberg (talk) 12:37, 14 September 2008 (UTC)

The discussion of a merger should have been located at the other article, which before August 5th was mostly taken up with a discussion of the Dominance versus Overdominance hypotheses. That discussion was eliminated without being replaced when the article was largely eliminated and redirected to a merger discussion here. 24.7.41.12 (talk) 08:00, 15 September 2008 (UTC)

Merge proposal II

Dominance has a standard meaning in Mendelian genetics, namely the phenotypic expression of that allele versus other haplotypes which may or may not be functional. Essentially, the ration of offspring between two heterozygotes will yield a 3:1 phenotypic ratio.

Overdominance is nonmendelian and has more to do with evolution and adaptation with respect to fitness and Darwinian selection. The overdominant idea suggests that a heterozygote is more fit than either homozygote. The increase of the fitness of the heterozygote genotype (compared to either homozygote) is, in this instance, the phenotype. This is synonymous with heterozygote advantage, the extension of which, as I understand, is that selection is balancing and the fitness of the hetero versus homozygote is additive.

Heterozygote advantage: Overdominance as Neg. Freq. Dependent Selection:Rare allele advantage

The opposite of overdominance being underdominance, then, the underdominant phenotype of the heterozygote genotype would be less fit than either homozygote (heterozygote disadvantage or homozygoe advantage). This idea runs parallel with incomplete dominance but again, the pheontype is related to fitness, for example the hairless gene of dogs is incomplete dominance yielding a non-mendelian ratio of offspring, the dead homozygote recessive allele is neither dominant nor recessive. The idea of fitness being the phenotype makes it either a net increase or decrease in fitness of either homozygote. An increase is overdominance. A mean value of fitness between the two haplotypes would be more like incomplete dominance, for which allele is truly dominant? A net decrease in fitness when compared to either homozygote would be underdominance and would also drive balacing selection much like overdominance. So in my opinion the two terms are synonymous.(Asmit7777 (talk) 05:22, 29 April 2009 (UTC)).

Sorry, but I think you are wrong that overdominance and heterozygote advantage are the same thing. Overdominance is certainly not just related to fitness. Also, "underdominance" (the first time ever I see that term) is not at all the same thing as incomplete dominance. There can be lots of explanations for non-Mendelian offspring ratios, but incomplete dominance is not one of them (incomplete penetrance, for instance, or prenatal mortality of some genotypes).

Concerning dominance, classic quantitative genetics is very clear about this:

• m = the mean value of two homozygotes AA and aa for gene A carrying different alleles
• d = the additive-genetic value, such that AA = m+a and aa = m-a
• h = the dominance deviation, such that Aa = m+h

Note that a is defined to be positive, whereas m and h can have any possible value. Now we can define the following situations:

• No dominance: h=0
• Incomplete dominance: |h|<a
• complete dominance: |h|=a
• overdominance: |h|>a

See: Mather, K. (1982). Biometrical Genetics. The study of continuous variation. London: Chapman and Hall. pp. xiv+396. ISBN 0-412-22890-4. {{cite book}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)

--Crusio (talk) 14:27, 29 April 2009 (UTC)

Statement about Heterozygote advantage for sickle cell trait

This statement under the "Heterozygote advantage in human genetics: Sickle-cell anemia" heading implies that individuals with sickle cell anemia (that is, two sickle hemoglobin beta alleles) have a survival advantage during malaria infection, just like those with sickle cell trait (heterozygotes with one sickle allele and one normal allele): "However, those with two alleles for SCA may survive malaria, but will typically die from their genetic disease unless they have access to advanced medical care."

This is not the case. In the scientific/medical community, it is well known that malaria infection exacerbates the symptoms of sickle cell anemia,so that being homozygous for the sickle allele is actually a disadvantage in terms of malaria infection.

Instead, this sentence should read "In contrast, those with two alleles for SCA are at a disadvantage both in the context of malaria infection (as infection exacerbates their genetic disease ) and in their everyday lives, as they will typically die from their genetic disease unless they have access to advanced medical care."

If no one objects, I will make the change in the next week.

Klontok (talk) 15:22, 17 July 2012 (UTC)

References

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Wording of "Theory"

When two populations of any sexual organism are separated and kept isolated from each other, the frequencies of deleterious mutations in the two populations will differ over time, by genetic drift. It is highly unlikely, however, that the same deleterious mutations will be common in both populations after a long period of separation. Since loss-of-function mutations tend to be recessive (given that dominant mutations of this type generally prevent the organism from reproducing and thereby passing the gene on to the next generation), the result of any cross between the two populations will be fitter than the parent.

Most of this reads like a heterosis article.

It is highly unlikely, however, that the same deleterious mutations will be common in both populations after a long period of separation. - Outbred populations of the same species will have mostly the same allele frequencies. For example 17% of the deleterious mutations will differ across outbred populations, not most.

the result of any cross between the two populations will be fitter than the parent. - A fitter genotype at the loci where overdominance has occurred? This isn't made clear, it can be mistaken for fitter offspring resulting from the cross? If that is the case the relation to inbreeding depression and heterosis should be clearer. Crosses do not show higher fitness unless inbreeding depression in the parental groups has occurred. 2A02:C7F:2DA6:0:F8FD:21F3:C59:848F (talk) 01:54, 14 May 2022 (UTC)