One mutation may drive you insane or make you smarter

I like to say, "physicists don't care about the details, chemists say the details do matter, and biologists say the details are a matter of life and death."

Bill Parson recently told me about a striking example of how one mutation [substituting a single amino acid for a different one in a protein] can really change things, for better or for worse. I reproduce below the relevant paragraph from this paper.

Crystal Structures of Human 108V and 108M Catechol O-Methyltransferase 
K. Rutherford, I. Le Trong, R.E. Stenkamp, W.W. Parson

Human COMT contains a common polymorphism at residue 108, which can be either valine (V) or methionine (M).^{22, 23 and 24} Approximately 25% of U.S. and Northern European Caucasians are homozygous for the 108M allele, which is much less common in African and Asian populations.^25 and 26 The 108M allele has been linked with increased risk for breast cancer,^{27, 28, 29 and 30} obsessive–compulsive disorder,^31 and 32 some manifestations of schizophrenia,^{33, 34, 35, 36 and 37} and increased sensitivity to pain,^38 and 39but it has also been linked with improved prefrontal cognitive function, especially in working memory.^40 and 41 It appears to be linked particularly strongly to neuropsychiatric dysfunction in velocardiofacial syndrome, a chromosomal disorder resulting from the deletion of multiple contiguous genes, including COMT, from one copy of chromosome 22. ^{37, 42 and 43} A haplotype involving the 108V allele and two noncoding COMTpolymorphisms has been associated with increased risk for schizophrenia, possibly because it results in diminished mRNA expression or translation. ^{44, 45, 46, 47 and 48}

One might wonder about connections with VHL disease, which it has been suggested may play a role in the Hatfield-McCoy feud. I first learned about this famous family feud in the book Outliers.