Hemoglobinose S mutation position

Question

[sacha]

The mutation which occurs in sickle-cell anaemia is a good example of Mendelian disease. From books , from wikipedia and many genetics documentation, you will read :

The sickle-cell disease occurs when the sixth amino acid, glutamic acid, is replaced by valine to change its structure and function; as such, sickle-cell anemia is also known as E6V

So I checked myself from UCSC genom browser , which show it's E7V !

I also search from clinvar which confirm the genom browser :

So my question.... Am I wrong ? Or all books are wrong ?

[GenoMax]

UniProt sequence clearly has E in position 7.

Answer 1

[WouterDeCoster]

From wikipedia:

The gene defect is a known mutation of a single nucleotide (see single-nucleotide polymorphism - SNP) (A to T) of the β-globin gene, which results in glutamic acid (E/Glu) being substituted by valine (V/Val) at position 6. Note, historic numbering put this glutamic acid residue at position 6 due to skipping the methionine (M/Met) start codon in protein amino acid position numbering. Current nomenclature calls for counting the methionine as the first amino acid, resulting in the glutamic acid residue falling at position 7. Many references still refer to position 6 and both should likely be referenced for clarity.

[GenoMax]

@sacha must not have read the wikipedia entry all the way through :-)

[sacha]

Lol ! You are right ! I no longer use CTRL+F to search a keyword in wikipedia !

[GenoMax]

You are going to disappoint many who are looking for a mystery based on the title.

BTW: Hemoglobinose .. is that a new kind of haemoglobin? Perhaps that has the E6V change.

[WouterDeCoster]

Based on a quick google it's a French type of haemoglobin, probably genetically linked to drinking wine and surrendering?

(I apologize for my Friday-evening humour.)

[sacha]

Hemoglobinose is another name of the disease: sickle-cell anaemia

[GenoMax]

Thanks for the clarification. Search seems to equate (assuming the translation from French to English is working right for pages) Hemoglobinose to Haemoglobin (or more generally haemoglobinopathies, of which SCA is one).

I had thought that the word in title was a typo. My apologies.

[sacha]

As you said , HGVS said :

the Methionine encoded by the translation initiation site (start codon) is numbered as residue 1 ("Met1" or " M1" )

So, this is a history mistake ! Mixed with bed / vcf / sam coordinate discordance, it'll be a big mess !