Some people never learn: the genetics of learning from our mistakes

In its simplest sense, we imagine that learning occurs through a series of positive and negative rewards. Some actions lead to pleasure, others to pain, and it seems reasonable to expect that people will repeat the actions with pleasurable results and avoid those that ended in pain. Yet, we all know people who aren't deterred by the idea of punishment. We all know people who never seem to learn. Could there be a physical reason, hidden in their genes? In December 2007, Science published a study by Klein et. al. (1) where they asked if a specific genotype at a location called "DRD2-TAQ-IA" affected an individual's ability to learn from mistakes. I'm intrigued by this question because I'm interested, in general, in the biology of learning and how this information can be applied to the practice of teaching. If we know that students with some genotypes learn better one way and students with other genotypes learn better another way, perhaps we can use this information to tailor our teaching and help all students get the most out of their time in the classroom. Some background on the study In this study, the participants were 26 males, who were placed into two different groups according to their genotype. The group with the A1- genotype had 12 members and the other group, with the A1+ genotype had 14. The kind of genetic change that was used to group the different guys is called a RFLP. I have another post that describes RFLPs in more detail. In short, for this RFLP, the enzyme TaqI can cut a guy's DNA and make two fragments (A1+) if he has an A at a specific position on chromosome 11. If a guy has a G at that position, for both copies of chromosomes 11, then the enzyme won't cut the DNA, we won't see two fragments, and he gets sorted into the A1- group. There are a few more details that are also important here. First, we all have two copies of chromosome 11. A person who has a TaqI site on both chromosomes would be called A1+/A1+, a person who only has a TaqI site on one chromosome would be A1+/A1-, and a person without any TaqI recognition sites would be A1-/A1-. As far as I can tell, this authors of this study grouped everyone with a TaqI site into the A1+ group and everyone else into the A1- group. Usually, these studies would put people into three different groups (A+/A+, A+/A-, and A-/A-) but that wasn't done here. The study and some of the results In one of the main experiments, Klein et. al. tested the ability of the A1+ and A1- guys to recognize certain symbols in 20 different trials and concluded that the guys with the A1+ allele were more likely to make a mistake and pick the wrong symbol. In the graph below, A was right, B was wrong and one group was better at avoiding B than the other group. In other words, the A- guys were better at avoiding mistakes (they avoided B). That part of the study seemed fairly straightforward and seemed to be confirmed by the other experiments. Klein and coauthors mentioned that another study found that the DRD2-TAQ-IA+ allele (polymorphism) was associated with fewer dopamine receptors on the surface of brain cells. They speculated that having more dopamine D2 receptors makes one more sensitive to negative feedback and better able to learn from mistakes. They also cited studies that claimed to link reduced dopamine receptor density with other conditions like drug addiction, obesity, and compulsive gambling. It all sounds pretty horrible. And yet... The problem I found a problem with the study that seems to have been overlooked. Many of the conclusions in the paper result from the notion that this polymorphism is located within the dopamine D2 receptor gene and somehow affects either the functioning of the dopamine D2 receptor or the levels of this protein. But when I looked in OMIM (even last December), I found that the genetic change described by Klein isn't located in the dopamine receptor gene (3). In fact, it's possible that the DRD2-TAQ-IA polymorphism doesn't have any effect on the dopamine D2 receptor. From OMIM (3):

Neville et al. (2004) showed that the TaqIA RFLP is located in a novel kinase gene designated ankyrin repeat and kinase domain containing-1 (ANKK1; 608774), located downstream of the DRD2 gene in chromosome band 11q23.1.

I looked at dbSNP to investigate the frequency of the A1+ allele in different populations. In dbSNP, I found that the percentage of A1+ people varies from 10% in Europeans to as high as 50% in Asian populations (4). It seems hard to believe that such a large fraction of people would have a harder time learning from their mistakes or suffer from all the other problems that were attributed to this allele. Learning where this genetic change is really located makes me wonder if some of the many qualities that are attributed to the DRD2-TAQ-IA polymorphism are real or if those qualities were partly inferred because researchers thought this change was located in a receptor for dopamine. As long as we're talking about learning from mistakes, perhaps someone should suggest to Klein et. al. and the reviewers from Science that they consider learning how to use OMIM. References:

1. Klein, T. (2007). Genetically Determined Differences in Learning from Errors. Science, 318(5856), 1642-1645.
2. Neville, M. J.; Johnstone, E. C.; Walton, R. T. : Identification and characterization of ANKK1: a novel kinase gene closely linked to DRD2 on chromosome band 11q23.1. Hum. Mutat. 23: 540-545, 2004. PubMed ID : 15146457
3. OMIM, dopamine receptor D2, accessed 6/17/2008
4. http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=1800497