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As my question in SO was closed and asked to be posted in this forum, I am posting it here

I am not from the bioinformatics domain. However, for the sake of analysis, I am trying to pick up certain basics related to the GT field in the VCF file.

I know we have a field called Alleles. May I know under what circumstances GT takes a certain values and how they are called? Can you confirm my understanding?

Ref Alt    GT   Name 
A    A     0/0  Homozygous
A    G     0/1  Heterozygous (does 1/0 also mean the same?) What's this 0 and 1 actually?
A   [C,CA] ??    ??
??   ??    1/1  HOM_ALT? How and why? 

Can the experts here help me to fill the question marks and also help me understand with the Ref and Alt combinations when a genotype can take a value of 0/0 or 1/0 or 1/1 or 1/2 etc and what are the names for those values? Like when it is called home_alt etc

Any simple explanation for beginner like me (with no background in bioinformatics/biology) can be helpful

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You can get most of the info from this paper. See Fig. 1 and the surrounding text. Quoting from there, "GT, genotype, encodes alleles as numbers: 0 for the reference allele, 1 for the first allele listed in ALT column, 2 for the second allele listed in ALT and so on."

In your case, the reference allele, here a single nucleotide, is A. When the alternate allele is also A, the genotype GT is reference, or 0. There are 2 copies of each allele in the human genome in non-sex chromosomes chr1-chr22, hence 0/0, or homozygous reference or HOM_REF.

When ALT=G, and the GT column is 0/1, this means that you have 1 reference allele (0), and 1 alternate allele (1). This means that you have A on one copy of this locus, and G on another. The convention is write GT field in ascending order, so 0/1 rather than 1/0. This is called heterozygous, or HET.

When ALT=C,CA, the GT is probably 1/2, because there are 2 alternate alleles, and I assume we continue with the same chromosome present in 2 copies. This means there are no reference alleles here at all, only alternate alleles. It is a heterozygous genotype composed of two different ALT alleles, or HET_ALT. Note that it is not enclosed in square brackets in the vcf file format: A <tab> C,CA <tab> 1/2 ....

Finally, these are some examples of HOM_ALT:

A    C     1/1
A    G     1/1
A    CA    1/1

This means that the same ALT allele (either C, or G, or CA) is present in 2 copies. There is no reference allele present. This is called homozygous alternate genotype.

In general, the name homo means the same, and hetero means different, in the context of genotypes.

REFERENCES:

Danecek P, Auton A, Abecasis G, et al. The variant call format and VCFtools. Bioinformatics. 2011;27(15):2156-2158. doi:10.1093/bioinformatics/btr330 : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3137218/

SEE ALSO:

VCF - Variant Call Format
What Does Genotype ("0/0", "0/1" Or "1/1") In *.Vcf File Represent?
Difference between 0/0 and ./. for genotype in VCF
1/2 in VCF genotype field?

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  • $\begingroup$ upvoted and accepted @Timur Shtaland. Appreciate your help. Am new to bioinformatics and can I reach out to you for further questions if any. $\endgroup$ – The Great Sep 14 '20 at 12:18
  • $\begingroup$ shtaland - have you used hail tool for genomic data analysis? $\endgroup$ – The Great Sep 14 '20 at 12:24
  • $\begingroup$ @TheGreat It is best to just post here in general. This way, you will get the best answer possible (which will most likely come from bioinformatics experts in the specific field). I visit occasionally both SO and bioinformatics.SE. Another good place to post is Biostars, which is not connected to SO/SE. $\endgroup$ – Timur Shtatland Sep 14 '20 at 12:34
  • $\begingroup$ @TheGreat Sorry, I am not familiar with hail tool. Maybe it is worth asking another question here - hopefully you will get an answer. Good luck! $\endgroup$ – Timur Shtatland Sep 14 '20 at 12:36
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0 and 1 is just a way of coding the reference (0) and alternate (1) allele. These could be A/G, C/T etc. It's just a simplified way of expressing the different alleles.

0/1 and 1/0 functionally mean the same thing (that the individual is a heterozygote) - since the genotype is unphased, the alleles aren't ordered. The / symbol tells you the genotype is unphased. However, in practice, a heterozygous genotype is always written as 0/1 as a matter of convention. 0/0 is referred to as homozygous reference, and 1/1 as homozygous alternative.

0|1 and 1|0 do mean something different, since the pipe symbol | tell us the order of the alleles matters.

Occasionally you will have multi allelic positions, where you have more than one alternate allele, and therefore the field will look like:

Ref   Alt
A   [C,GT]

The extra alt allele is given the number 2, so in this case if an individual had the genotype CT then their genotype code would be 0/2.

Full detail is given in the official VCF specification page.

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  • $\begingroup$ upvoted for the help $\endgroup$ – The Great Sep 14 '20 at 12:19

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