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I am researching a fatty acid amide hydrolase (FAAH) SNP RS324420 and FAAH out microdeletion that together lead to reduced pain sensitivity and reduced anxiety (Moreira et al 2008).

The causative mutations for this new pain insensitivity disorder are: the co-inheritance of (i) a microdeletion in dorsal root ganglia and brain-expressed pseudogene, FAAH-OUT, which we cloned from the fatty-acid amide hydrolase (FAAH) chromosomal region; and (ii) a common functional single-nucleotide polymorphism in FAAH conferring reduced expression and activity. Circulating concentrations of anandamide and related fatty-acid amides (palmitoylethanolamide and oleoylethanolamine) that are all normally degraded by FAAH were significantly elevated in peripheral blood compared with normal control carriers of the hypomorphic single-nucleotide polymorphism. The genetic findings and elevated circulating fatty-acid amides are consistent with a phenotype resulting from enhanced endocannabinoid signalling and a loss of function of FAAH. Our results highlight previously unknown complexity at the FAAH genomic locus involving the expression of FAAH-OUT, a novel pseudogene and long non-coding RNA.

Br J Anaesth. 2019 Aug; 123(2): e249–e253. Published online 2019 Mar 28. doi: 10.1016/j.bja.2019.02.019

I would like to know, theoretically if CRISPR was used to edit these genes in humans to allow reduced anxiety and pain sensitivity, 'what is the probability that a recurrent mutation would cause the wild-type allele to reemerge in this gene',

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  • $\begingroup$ Welcome to Biology.SE! Please take the tour and then go through the help pages starting with How to Ask questions effectively on this site and edit your question accordingly. In particular, speculative questions lead to "answers" that are opinions (rather than factual) — this makes your question as currently written off-topic for this site. In addition, questions should be clear (e.g. abbreviations and acronyms should be defined). Finally, summarizing what you have already learned about your question will demonstrate that you've done the expected prior research. Thanks! 😊 $\endgroup$ – tyersome Oct 18 '20 at 18:05
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    $\begingroup$ @tyersome I appreciate the question is worded in a speculative way. However, I don't agree that the question is fundamentally speculative in nature - I think it could be reworded to 'what is the probability that a recurrent mutation would cause the wild-type allele to reemerge in this gene', which could certainly be answered using a simple population genetic model. In that sense, I think it is an interesting and relevant question, $\endgroup$ – user438383 Oct 19 '20 at 22:22
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    $\begingroup$ @MissEllieKarslake. I think your question is an interesting one, but we might need some more details to give it a proper answer. Please can you include a) what organism you are interested in, b) which particular SNP and deletion you are interested in, c) whether you are interested in a wild or lab population. Thank you. $\endgroup$ – user438383 Oct 19 '20 at 22:34

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