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Classic examples of mendelian inheritance are genetic diseases such as sickle-cell anemia, Tay-Sachs, cystic fibrosis, and xeroderma pigmentosa. For some of these diseases, it is believed that they evolved because the genes gave a beneficial effect that outweighed the rare occurrence of the disease (e.g sickle cell and protection against malaria).

However, all of these are examples of uncommon phenotypes, usually less than 1% of the relevant population (where it is most common) has those diseases. I'm interested in examples of mendelian inheritance where variation is common (all of the relevant phenotypes have, say, >5% frequency or something like that).

Consider eye color. In European populations both blue and brown eyes are common phenotypes. Many people have probably experienced a typical high-school class of biology, where this was introduced as an example of mendelian inheritance with brown eyes being dominant and blue eyes being recessive. However, modern studies (for example, genome-wide association studies) show that things like eye, hair and skin color are all polygenic traits. See for example (Sulem, ..., Stefansson, 2007).

Throughout the years I've heard of other traits that some said were examples of mendelian inheritance. Being able to roll the tongue, for example. This question was inspired by this recent question where absence of teeth (Hypodontia) was taught to the OP as an example of a dominant trait. The current answer says that hypodontia is probably an example of a polygenic trait that interacts with certain environmental effects. This got me wondering whether there even are examples of common mendelian variation.

I don't quite know the best way to phrase it, but my question is the following:

Are there any examples of human phenotypes that are due to mendelian inheritance where all of the phenotypes are common?

Take eye color as an example again. By common, I mean that both blue eyes and brown eyes are common (over, say, 5% in for example Sweden). On the other hand, for example Tay-Sachs disease occurs only about 1 in 3,500 among Ashkenazi Jews where it is most common, according to Wikipedia. Way less than even 1%.

Preferably I want it to be verified by modern genomic studies (such as GWAS) that it is an example of mendelian inheritance. If such an example does not exist, then I will accept any answer that provides modern, relevant scientific literature that explores this topic. For example, it might explain why we would not expect to see common variation due to mendelian inheritance.

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  • $\begingroup$ Generally, you don't need a GWAS to detect Mendelian traits (though it can and will quite reliably, precisely because those genes are Mendelian). That's why common Mendelian traits were identified before GWAS. $\endgroup$ – kmm Jul 25 '18 at 14:12
  • $\begingroup$ @kmm Fair enough. But there were also traits that were claimed to be Mendelian, and after GWAS were discovered to not be. (Though, to be fair, that could simply be bad practice by the people who claimed that, and perhaps it was not consensus.) But you're right. It doesn't have to be GWAS evidence. Just simply some good evidence that is consistent with modern findings. $\endgroup$ – Eff Jul 25 '18 at 15:23
  • $\begingroup$ GWAS aside, what you are asking for isn't clear to me. If I understand correctly, you are looking for phenotypes that are Mendelian (i.e., not complex traits), but which also have common alleles (I imagine 50:50 would be ideal). $\endgroup$ – kmm Jul 25 '18 at 23:12
  • $\begingroup$ @kmm Well, for example take any population, say The Netherlands. Imagine if a person from this population could either have blond hair or dark hair. Both phenotypes are fairly common. Then imagine if it were discovered that blond/dark hair was Mendelian, then that would be a nice example (It happens not to be the case; hair color is actually polygenic). Now I want to know if there are any examples like that. Sure, I guess 50:50 would be great, but I would be satisfied with, say, 95:5 or 90:10. (If you wish, you can edit my question to make it more clear) $\endgroup$ – Eff Jul 26 '18 at 7:11
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    $\begingroup$ Depending on how broadly you want to bin a phenotype, and what you mean by "all the phenotypes", hemoglobin disorders are among the most common mendelian traits. In Cyprus, for example, I believe around 17% of the population is heterozygous for a hemoglobinopathy. $\endgroup$ – De Novo Mar 6 '19 at 23:36
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Earwax consistency is an example of a monogenic trait with dimorphic phenotypes in humans -- "wet" and "dry" -- where both phenotypes are globally common, though allele ratios are highly variable between human populations. The population genetics and molecular basis of this trait are discussed at length by Dr. John H. McDonald as part of a series on the myths of human genetics (archived version here). I reformat his discussion in my answer.


In The dimorphism in human normal cerumen, Matsunaga summarizes 30 years of research into the earwax of Japanese families, with two major observations:

  1. Dry earwax parents never have wet earwax children, suggesting the genetics underlying the wet phenotype are dominant to those underlying the dry phenotype.
  2. Because the allele for wet earwax is relatively rare in the sampled families, it is likely that most wet earwax parents are heterozygotes. Following from this, if the trait is monogenic with two allele variants, we expect a 3:1 ratio of wet to dry children in wet × wet parent crosses, and a 1:1 ratio of wet to dry children wet × dry parent crosses. Indeed, this is observed.

$$\begin{array}{c|c|c|} \text{parents} & \text{wet children} & \text{dry children} \\ \hline \text{w×w} & 35 & 12 \\ \hline \text{w×d} & 205 & 195 \\ \hline \text{d×d} & 0 & 634 \\ \hline \end{array}$$

These results were later corroborated in Native Americans --
Cerumen in American Indians: Genetic Implications of Sticky and Dry Types

$$\begin{array}{c|c|c|} \text{parents} & \text{wet children} & \text{dry children} \\ \hline \text{w×w} & 32 & 6 \\ \hline \text{w×d} & 20 & 9 \\ \hline \text{d×d} & 0 & 42 \\ \hline \end{array}$$

And in a different Japanese cohort --
Distribution and inheritance of earwax types: a study on inhabitants in Awa District, Chiba Prefecture

$$\begin{array}{c|c|c|} \text{parents} & \text{wet children} & \text{dry children} \\ \hline \text{w×w} & 27 & 3 \\ \hline \text{w×d} & 137 & 109 \\ \hline \text{d×d} & 0 & 345 \\ \hline \end{array}$$

In the early 2000s, the molecular basis of human earwax consistency was elucidated in three major publications.

  1. Toshida et al. mapped a single locus on chromosome 16
  2. Yoshiura et al. identified a SNP at position 538 in the coding region of ABCC11. At this site, G corresponds to a wet earwax phenotype, whereas A leads to a dry earwax phenotype. A less common allele representing a deletion of 27 nucleotides in exon 29 also yields a dry phenotype.
  3. Toyoda et al. found that the 538G>A transition encodes arginine in place of glycine, resulting in a loss of glycosylation in the mutant protein, leading to deficient cellular localization, rapid degradation, and loss of function.

To directly address your question,

Are there any examples of human phenotypes that are due to mendelian inheritance where all of the phenotypes are common?

I point you to the tables above, as well as Table 1 from Cerumen Phenotypes in Certain Populations of Eurasia and Africa, which shows that the frequency of the dry allele ranges from 59% to 89% across diverse human populations --

Table 1 from Ibraimov 1991

To conclude, human earwax consistency is a dimorphic trait controlled by a single gene, where both phenotypes are common across human populations.

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    $\begingroup$ Thank you for the answer (upvoted and accepted), and nice site that "Myths of human genetics" by Dr. McDonald. $\endgroup$ – Eff May 7 at 11:54

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