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Studying Schizophrenia and reading some papers discussing polymorphisms in the 5HT-2A receptor gene (HTR2A). Specifically, the authors mention A-1438G, T102C, his452tyr. How does one best take processed genetic data, such as on 23andMe, or the entire raw data with Nebula to determine which variants are carried? 23andMe allows access to raw data and you can search for the gene by HTR2A where there is a list of rs markers such as rs9595552 and rs17069218 and their genomic positions 47407430 and 47408350, respectively. How do I take A-1438G, T102C, his452tyr and relate them to either the rs number or genomic position? Supposing they aren't on the list and I get a whole-genome sequencing done by Nebula, how would I go about finding these residues? I know that HTR2A is on chromosome 13q14-21. I understand the first part 'chromosome 13', but not the rest. Nor do I understand how I would go about navigating the raw genomic data.

Edit: Luckily, I was able to use Google to track down these relationships.
rs6313 = T102C
rs6311 = A1438G
rs6314 = his452tyr
when I looked to the data on 23andMe, online it yielded:
rs6313 = T102C ; A or G ; AA
rs6311 = A1438G
rs6314 = his452tyr ; G or A ; GG
I was able to download the complete raw data and search the text file for the middle one yielding:
rs6313 = T102C ; A or G ; AA
rs6311 = A1438G ; TT
rs6314 = his452tyr ; G or A ; GG
Now the last one appears apparent. We are clearly discussing the amino acid sequence. Histidine (H) has two possible codons, CAU and CAC. Tyrosine has two possible codons, UAU and UAC. Meaning that the variation lies in the first position, with a G in the DNA yielding histidine and an A giving tyrosine. So G or A is what we are looking for in the DNA sequence from 23andMe and all is well.
If we then try and apply this same process to the other two polymorphisms, assuming they are amino acids and not nucleotides, it doesn't work.
alanine(A): GCU, GCC, GCA, GCG
glycine(G): GGU, GGC, GGA, GGG
threonine(T): ACU, ACC, ACA, ACG
cysteine(C): UGU, UGC
For alanine/glycine, the nucleotide variation would be occurring in the second position, G/C. Yet the 23andMe data says genotype is TT. Therefore I believe it is correct to assume A/G is referring to nucleotides in the DNA.
The same would apply for threonine and cysteine, for two out of three of the nucleotides must be the same and this is not the case. Assuming instead they are nucleotides is compatible with the data from 23andMe; A or G and AA.
That being said, I am aware that the promotor does not always lie at the beginning of a gene, but I do not know where else it can lie. Can it lie at the end? A-1438G is in the promoter, T102C in exonI, and his452tyr in exonIII. Converting his452tyr we have (452*3-2=1354) G-1354A. Putting them in order: exonI T102C, exonIII G-1354A, promoter A-1438G. Does this sound correct?

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    $\begingroup$ I'm not exactly sure what you're asking for, perhaps you could structure your question a little better. But searching for your gene at dbSNP seems like a good start. That lists you all gene variants currently mapped to the specific gene. Example: ncbi.nlm.nih.gov/snp/?term=HTR2A. After searching you can also click Varview to view the genome position of the gene and all its variants. $\endgroup$
    – gaspanic
    Jan 1, 2022 at 17:33

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If you go to the gene at Genbank you will see that the gene has a few variants, which are based on differing intron/exon boundaries. The 13q... is the position based on karyotype analysis. You can relate this to straight genome positions to some extent, but you would need to determine the start codon and the intron/exon boundaries for your encoded protein.

There are a few possibilities:

  1. The positions are amino-acid substitutions - They are related to the genomic sequence by the coding position starting with the start codon ATG (Met) and working from there. In this case it would be Alanine to Glycine at amino-acid 1438 of the protein sequence. However, if you look at the CDS regions and go to the linked proteins (/protein_id=NP_XXXXXXXX) you will see that there are only 430ish amino-acids in the sequence. The His425Tyr is certainly an amino-acid substitution of this sort, the others might not be.
  2. The positions are raw coding positions. A highly conserved single base substitution at the designated site. This would be for the coding sequence only. You would take the exons only and count bases from the A of the start ATG.

I've not tried to access the 23-and-me data, so I don't know how it works, but the genomic position will be starting from the first base in chromosome 1 and counting up I think. Generally data of this sort will be analysed using a specific set of tools in a bioinformatics system.

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  • $\begingroup$ Thank you for your answer, bob1. I updated the original post if you can check my work that would be helpful. I may have to update the post in the future if there is an instance where Google does not yield a rs number for the polymorphism in question. $\endgroup$ Dec 31, 2021 at 18:05

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