[deleted] t1_ja7y91i wrote
[deleted]
fingawkward t1_ja8foyo wrote
It was my understanding that being heterozygous for sickle cell confers advantage in resistance to malaria while homozygocity causes sickle cell disease.
sparky_1966 t1_ja8p8n1 wrote
You are correct, heterozygous provides some protection from malaria and homozygous causes sickle cell. The heterozygotes are still not normal and are less healthy than normal people, but the negative pressure from malaria is strong enough that it's a net gain.
sa2bcity t1_ja8x9in wrote
You are right. In this case, however, the sickle-cell allele is the one that confers the advantage.
[deleted] t1_ja8plrr wrote
[removed]
TestTubeRagdoll t1_ja8pmnk wrote
> There are some disorders where the normal allele in heterozygotes confers some advantage, such as with Huntington's disease. Wexler, N. S., et al. (1987). Homozygotes for Huntington's disease. Nature, 326(6109), 194–197. https://doi.org/10.1038/326194a0
Just wanted to point out that this is a pretty outdated reference (from before the causative gene for HD was actually identified - they had a rough idea of the locus based on linkage analysis in HD families). As far as I am aware, there isn’t any strong evidence that the normal allele in heterozygotes confers an advantage in HD - and the article you linked actually states that homozygotes and heterozygotes appear to have the same phenotype, suggesting a true dominant condition, rather than one where heterozygosity is advantageous. There is a caveat that homozygotes for HD are quite rare, so studies involving them can be somewhat small.
sa2bcity t1_ja8wljh wrote
Yes, there are flaws with the article I referenced. There are other articles that suggest a more negative clinical course for homozygotes.
Squitieri, F., et al. (2003). Homozygosity for CAG mutation in Huntington disease is associated with a more severe clinical course. Brain, 126(4), 946–955. https://doi.org/10.1093/brain/awg077
TestTubeRagdoll t1_ja92zob wrote
Yes, this study makes the point better, although it's still small (n=8 homozygotes), and relies on retrospective analysis of clinic records.
Based on that study, it does look like there could be faster progression in homozygotes, although I don't know if there's enough data to argue that the normal allele is specifically conferring an advantage, as opposed to simply a dose effect of having 2 copies of the mutant allele.
It's also worth noting that not all studies show this same trend. For example, a 2019 Neurology study (https://n.neurology.org/content/neurology/92/18/e2101.full.pdf), which was somewhat larger (n=28 homozygotes) and used patients who are part of the EHDN Registry Database (ie using standardized data collection protocols for clinical data) did not see a difference in disease progression between homozygotes and heterozygotes.
Viewing a single comment thread. View all comments