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Understanding sickle cell trait
Entering edit mode
24 months ago
johnS • 0

I am new to genomic world, so my questions might be bit silly.

I been reading about it a lot recently and still I get confused with few things. And I feel if I am able to find answer for this, then I will be able to relate things. The sickle cell anemia is what I took as an example

Here is my understanding,

Sickle cell anemia is caused by the mutation of A with T, so if a person got this mutation from parental and maternal gene then for sure he/she will have sickle cell anemia.

So here A is the dominant and T is the recessive alleleā€¦

If person get both dominant allele A from both parents(homozygous dominant) === then no issues

If person get A from one parent and T from other parent (heterozygous ) === then he/she gets sickle cell trait

If person get both recessive allele (homozygous recessive ) === then he/she gets sickle cell anemia.

So based on my understanding this is how it should look like in a VCF file or other database

REF A (from the positive strand of the human reference genome)

ALT T (the variations seen)

So for the genotype

0/0 person got both A from both the parents == no sickle cell trait

0/1 person got A and T from either of the parents == sickle cell trait

1/1 person got T from both parents == sickle cell anemia.

Now the confusion started when I looked at the vcf file we have, so for the rsid rs334 (position of sickle cell mutation) it shows following



This not what I expected, I thought the reference allele and the sequence from parents (both mom and dad) will be looked in the forward strand in a VCF file. To clarify I looked at both Ensembl and dBSNP, which confused me even more.

Ensembl have the same thing what I saw in the VCF file

screen shot from dbsnp dBSNP I saw

RefSNP Alleles A/C/G/T (REV)

Ancestral Allele A

Contig Allele A

So in short , I am trying to find answers for following,

  • Is my understanding about sickle cell allele is correct ?

  • Why its showing like this in the VCF file ?

  • Please help me understand what I saw in dBSNP

Thank you

RNA-Seq genome SNP gene alleles • 211 views
Entering edit mode
24 months ago
Asaf 5.6k

This is because the HBB gene is on the minus strand so the genome, which is usually (well, always) the plus strand is T usually (REF) and A in the mutant (ALT) and the gene will have A in the usual case and T in the mutant replacing E->V.


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