Question: Understanding sickle cell trait
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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

REF T

ALT A,C,G

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

ADD COMMENTlink 11 months ago johnS • 0 • updated 10 months ago Asaf 5.6k
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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.

ADD COMMENTlink 10 months ago Asaf 5.6k

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