Posted by ABenis on January 31, 2012, 8:20 pm, in reply to "Re: Entanglement of N and A traits and the DRD3 gene"
Here is a summary of the two hypotheses. Note that the second hypothesis is more accurately "DRD3 codes for non-sanguinity by Mendelian dominant inheritance", rather than "... for sanguinity by Mendelian recessive inheritance" in order to allow for non-functional Ser9-associated haplotypes.
In our discussion, "A trait" includes the modulated trait A-/A=, on the assumption that the modulation is done on the fully-expressed A trait by epistasis from another locus. Trait P is also coded for by another locus, so the trait P can be present, or not, without affecting the scheme below.
1. In our Original hypothesis, an allele DRD3/Ser* codes for trait A by recessive inheritance. Thus:
Ser*/Ser* = trait A (+/- trait N)
Ser/Ser, Gly/Gly, Ser/Gly or Ser*/Gly = lack of trait A, therefore trait N by entanglement.
The above takes into account that not all Ser9 alleles code for trait aggression, with Ser* denoting the Ser9-associated haplotype identified by Costas et al.
2. In the Second hypothesis, the allele DRD3/Ser* codes for trait "non-N" (non-sanguinity) by Mendelian dominant inheritance. Thus:
Gly/Gly, Ser/Gly, Ser/Ser = trait N (+/- trait A)
Ser*/Ser* or Ser*/Gly = lack of trait N, therefore trait A by entanglement.
3. Common to both hypotheses:
Gly/Gly = individual must have trait N
4. Some corollaries:
In the first hypothesis, a non-sanguine individual must have genotype Ser*/Ser*. In the second hypothesis, a non-sanguine individual must have genotype Ser*/Ser* or Ser*/Gly. Common to both hypotheses: a Gly/Gly individual must be sanguine (have trait N).
In the first hypothesis, a non-aggressive (N or NP) individual can have genotype Ser/Ser, Gly/Gly, Ser/Gly or Ser*/Gly. In the second hypothesis, a non-aggressive (N or NP) individual may have genotype Gly/Gly, Ser/Gly or Ser/Ser. Common to both hypotheses: a generic Ser/Ser individual can either have or not have the A trait.
An individual having both N and A traits (NA or NPA type) must be Ser*/Ser* by the first hypothesis and either Gly/Gly, Ser/Gly or Ser/Ser by the second hypothesis.
An individual who is a generic heterozygote Ser/Gly must have trait N by the first hypothesis, but could have either trait N or A by the second hypothesis.
4. Examples that could be subject to testing:
* If an NP individual (? JD Watson) has trait N, lacks trait A and is of genotype Ser/Gly, then this is consistent with both hypotheses and not particularly helpful.
* But, if an individual has definite trait A (say, an NA dominant type) and is of genotype Ser/Gly, then this is consistent with the Second hypothesis but not the Original hypothesis.
* A sample of subjects with narcissistic personality disorder, NPD (? mostly NA types) would tend to be Ser9Gly homozygous Ser*/Ser* by the Original hypothesis.
* Another straightforward test would be "Gly/Gly individuals are sanguine" (consistent with both hypotheses).
5. Which of the two hypotheses is more likely? In the First Hypothesis, the Ser allele coding for aggression should be substantial in Polymorphic geographic areas like the USA [Munafo et. al., 2003], which seems to be the case. In the Second hypothesis, the Gly/Gly genotype should be very common in Polymorphic areas, which seems not to be the case. So, perhaps our Original hypothesis remains the more likely one of the two.
6. Conclusion. Entanglement of the N and A traits introduces subtleties in the analysis of case-control studies and is likely to cause confusion as the (? two) genes coding for the traits become recognized.
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