How Can I understand which allele is dominant?

Question

[Fatemeh Nabizadeh]

I have 2 SNPs having no association with the disease of interest in our study. I don't know how can I find out which allele is dominant or recessive? There is almost no data about that in previous articles! Is there a database or anything to help me?

Answer 1

[WouterDeCoster]

Not all variants have either a dominant or a recessive effect. Those terms are just very specific cases of impact on the inheritance of a very limited subgroup of positions. A CFTR F508del mutation is recessive because you only get the disease (cystic fibrosis) if you inherit two deleterious alleles. An APP duplication is dominant because you get the disease (Alzheimer Disease) as soon as you inherit one duplicated allele.

In contrast, most SNPs are just neutral (or have a small effect on the risk of disease) so cannot be classified as either dominant or recessive. Since you write that your SNPs are not associated with the disease then I suspect that your SNPs are in this last category.

[Fatemeh Nabizadeh]

Thank you WouterDeCoster! So what should I do for haplotype analysis? I thought that if I know which allele is dominant or recessive, I can resolve my problem! For Example if the T allele is dominant for each SNP, in a patient having T/C for SNP1 and T/C for SNP2, I can report her/his haplotype as T/T. How about this one: If the T allele is wild type for each SNP, in a patient having T/C for SNP1 and T/C for SNP2, I can report her/his haplotype as T/T.

[WouterDeCoster]

So what should I do for haplotype analysis? I thought that if I know which allele is dominant or recessive, I can resolve my problem!

There is not necessarily a link between haplotype analysis and dominant or recessive inheritance of a variant-associated trait.

For Example if the T allele is dominant for each SNP, in a patient having T/C for SNP1 and T/C for SNP2, I can report her/his haplotype as T/T.

No, that would be wrong. You don't know the phase of the alleles of SNP1 and SNP2. You don't know if these variants are in cis (same allele) or in trans (compound heterozygous). Even if you knew you are simplifying things you shouldn't. This patient has T/C for SNP1 and T/C for SNP2, regardless of dominant or recessive.

If the T allele is wild type for each SNP, in a patient having T/C for SNP1 and T/C for SNP2, I can report her/his haplotype as T/T.

No, again that would be wrong. This patient has T/C for SNP1 and T/C for SNP2, regardless of what the "wild type" is. Note that "wild type" is bad nomenclature for human genetics. You have the "reference allele" and "alternative alleles". But also the reference allele can be pathogenic!

[Fatemeh Nabizadeh]

You are right WouterDeCoster.

I exactly want to find out the relationship between my haplotypes and hormonal concentration. According to the data from SNP-analyzer, I have 3 haplotypes (2 SNPs): CT(h1)...TC(h2)...TT(h3) Every subject has 2 haplotypes (paternal & maternal), like this: h1,h2 or h1,h3 I'm confused since at last I have to report that just one haplotype affects the concentration of hormone. I do not know how to import my data into SPSS and how should I analyze.

[Fatemeh Nabizadeh]

I think maybe we can consider each individual as two. For example in a patient with T/C and T/T haplotypes, and hormone concentration of 2ng/dl: I would consider 2 subjects; 1. T/C with hormone concentration of 2ng/dl and 2. T/T with hormone concentration of 2ng/dl. What's your idea?

Answer 2

[h.mon]

If the SNPs have no association with the disease, it doesn't have a phenotype related to the disease, so it can't be classified as dominant or recessive.

[Fatemeh Nabizadeh]

Thank you h.mon!

Do you remember my last question?

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I have 2 SNPs which are in linkage disequilibrium. Each one containing 2 alleles (T and C). AND I have 4 genotypes: SNP1 T/C...SNP2 T/C ////// SNP1 CC...SNP2 T/T ///// SNP1 T/T...SNP2 C/C ////// SNP1 T/C...SNP 2 T/T. SNPanalyzer gave me 3 haplotypes as I mentioned; CT, TC and TT

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I thought that if I know which allele is dominant or recessive, I can resolve my problem! For Example if the T allele is dominant for each SNP, in a patient having T/C for SNP1 and T/C for SNP2, I can report her/his haplotype as T/T.

[h.mon]

I do remember your question. But you didn't fully explain your data. How many individuals did you genotyped / haplotyped and measured hormone concentration? I think you want to perform a logistic regression, but I don't know if you have enough data for it, nor if your data is appropriate - for example, are there confounding factors?

[Fatemeh Nabizadeh]

I have 88 individuals (45 cases and 43 healthy controls) whom their genotype, haplotope and hormonal levels were checked. I don't know much about statistics but I think a logistic regression test would be correct as I want to report an OR (odds ratio) at last. For example, I wanna conclude that TC haplotype is significantly associated with hormone concentration (p-value<0.05) and increases the risk (OR>1). I think maybe we can consider each individual as two. For example in a patient with T/C and T/T haplotypes, and hormone concentration of 2ng/dl: I would consider 2 subjects; 1. T/C with hormone concentration of 2ng/dl and 2. T/T with hormone concentration of 2ng/dl. What do you think?