Homozygous Indel/Snp & Heterozygous Indel/Snp

Question

[always_learning]

Hi All,

Can some one help me understand that what is homozygous indel/snp & heterozygous indel/snp ? And how do we term it homozygous indel/snp & heterozygous indel/snp after once its aligned with Genome ? Why can't all snp will be only heterozygous indel/snp ? And what could be significance of these terms in NGS study ?

Note: I am well aware about homozygous and heterozygous concept.

[Devon Ryan]

If you're "well aware" of the concepts of homo- and heterozygous, then it's unclear where your question actually arises. Regarding actually calling these variations, have you read any of the papers on SNP callers? BTW, all variation can be heterozygous, in most cases it's just unlikely for them all to be heterozygous at the same time.

[always_learning]

Ok, I understand the need of this question for myself so I thought of asking it here !! Sorry, If it was not clear for you. Yes, I read some paper on SNP calling but I was not asking about SNP calling too.

Answer 1

[Ashutosh Pandey]

Homozygous SNPs are the ones where both homologous chromosomes of the non-reference genome have the same allele and different from the reference genome. For mouse, most of the strains are inbred ( i.e. they have same allele for both the homologous chromosomes OR both the parents have contributed the same allele). So, if you compare a non-reference mouse to a reference mouse strain and if there is a SNP on one of the homologous chromosome then the same SNP will appear on the other homologous chromosome if the non-reference strain is inbred.

But in case of human, both father and mother can contribute different alleles and when you compare it with the reference allele, then it may be a case that the father's allele differ from the reference one but the mother's allele are same as that of reference. In this case, both homologous chromosomes have different alleles and one matches the reference and one does not. This will be an example of heterozygous SNP.

Hope it explains. Please feel free to ask questions.

Edit to include a drawing

AAATTTGGGCTTTAAA - Reference genome (Chr 1)

AAATTTGGGtTTTAAA - Non-reference genome (Chr 1 from father)

AAATTTGGGtTTTAAA - Non-reference genome (Chr 1 from mother)

Above is an example of Homozygous SNP ( t replaces C on both the Chr 1)

AAATTTGGGCTTTAAA - Reference genome (Chr 1)

AAATTTGGGtTTTAAA - Non-reference genome (Chr 1 from father)

AAATTTGGGCTTTAAA - Non-reference genome (Chr 1 from mother)

Above is an example of Heterozygous SNP ( t replaces C in father but not in mother)

[always_learning]

Thanks Ashutosh, So nice of you to explaining it in clear and precise way !! It helped actually. These are small concepts but some time it hurts alot for further understanding.

[potassiumiodide0990]

Hi Ashutosh... I have a doubt though..

AAATTTGGGCTTTAAA - Reference genome (Chr 1)

AAATTTGGGtTTTAAA - Non-reference genome (Chr 1 from father)

AAATTTGGGaTTTAAA - Non-reference genome (Chr 1 from mother)

In the above example t replaces C on father's Chr 1, a replaces C on mother's Chr1. Will this also be coined as homozygous snp or will it be compound heterozygous for that position? 1/1 in vcftools represents homozygous snp or compount heterozygozity?

[Jorge Amigo]

regarding NGS, I could understand that the zygosity concept is not as clear as the classic definition, so well explained here, says. if the classic concept is strictly ported to NGS, one would expect to see a 50:50 reads ratio supporting a heterozygous variant, and a 100:0 reads ration supporting a homozygous one. to be honest, I've never seen such a clear evidence on all the million variants we've called so far. instead, you always depend on a variant caller which estimates this ratio for you and determines whether the variant is homozygous or heterozygous. I always try stress on this when I report any results: this is always an estimation, and it can be a very good one, but it's not a direct measurement. after all, that's the main difference between NGS and capillary sequencing.

[bialexdegil]

How can I conduct this analysis in Galaxy. I have RILs (F7), father and mother sequences. Thank you

Answer 2

[ibseq12]

Hi just confused about this: AAATTTGGGCTTTAAA - Reference genome (Chr 1)

AAATTTGGGtTTTAAA - Non-reference genome (Chr 1 from father)

AAATTTGGGtTTTAAA - Non-reference genome (Chr 1 from mother)

why we don't info about the biallelic site on the reference genome - is it homo or heterozygous? E.g. could it be that the other allele on the reference is a "t"

thanks, ibseq