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I have a few questions I can't seem to get a straight answer to, regarding the .gen file format and also biology in general.

The .gen file format specifies SNPs for individuals.

Since each SNP has associated allele A and allele B, I assume that the file only contains Causative SNPs, and not Linked SNPs, since the former reside in the gene, and the later don't. Since each SNP in the file has an associated gene (actually genotype, some combination of allele A and B). Correct?

SNP indicate a single position in genome, so why can allele be identified with a sequence larger then one? Or does it indicate just a starting point, where each allele can be of different length, which can be greater than 1?

Allele should be a particular variant of a specific gene, but in other places I saw the definition "Alleles are alternative forms of a particular sequence.". The later seems more logical, if looking at the .gen file, but it's contradictory to the first statement. So, what's the correct definition?

EDIT:

After further research I came up with findings, demonstrated in an example row for .gen file:

--- rs200405949 10023   CCAA    C   0.249   0.745   0.007   0.005   0.84    0.155 ...

--- - chromosome number, which is missing because it can be inferred from the filename, belonging to each chromosome

rs200405949 - ID of the SNP - a single nucleotide which can vary between samples/people; there are usually only two possible variations, but in rare cases there is a third or even fourth - which are ignored in .gen?

10023 - allele pair (base pair) coordinate/position inside the said chromosome. Either both major and minor allele are made of a single nucleotide (in which case the SNP coordinate/position inside the said chromosome might coincide with this position), or one of the alleles will have more than one nucleotide and the other allele will be the same as the first nucleotide of the former allele - because we need only one distinct sequence, and all other combinations of same nucleotide length are automatically the other allele?

CCAA - (usually?) major allele - the most common allele (specifically in this context, a single nucleotide or a sequence of nucleotides) for a given SNP (or near it, i.e. somehow connected to it) IN the cohort in question, i.e. the cohort being all the samples/people in the experiment/.gen file (hence, the number of samples equals the number of triplet columns after the 5-th column onwards). It occurs in more than 50% of the times COMPARED to minor allele. Compared to minor allele, they both start with C - shouldn't they differ at this SNP position by definition? Also, more than one nucleotide is specified here - why? SNP always has one nucleotide...

C - (usually?) minor allele - the second most frequent allele (specifically in this context, a single nucleotide). The SNP site can be bi-allelic (mostly picked/studied), in which case the major and minor alleles are the only possible alleles, but some sites are tri- or quad-allelic - in which case we don't have the info for the third (and fourth) allele variants, but we know they are even less common then the major and minor alleles?

0.249 0.745 0.007 0.005 0.84 0.155 ... - each subsequent triplet of values then indicate likelihoods of homozygote CCAA/CCAA, heterozygote CCAA/C, and homozygote C/C genotypes (allele pairs) at this SNP, respectively, for one sample/person (each allele is present on one of the two copies of the said chromosome, either maternal or paternal). If one of the three values has a value 1 and the other two have 0, I guess this actual SNP was (somehow) tested for, hence we can be 100% sure which allele pair it is, and if not, then the probabilities were somehow deduced (e.g. from other, somehow related SNPs perhaps). What if they add up to less than one? Or even what if all of the three values are 0?

Are my conclusions correct? And what about the open question?

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  • $\begingroup$ Based on sciencedaily.com/terms/allele.htm, each gene can be represented by a set of alleles, and alleles are just alternative forms of a particular single-nucleotide sequence; and since they can posses 2 different forms for the given genome (resulting in a 3 distinctive combinations), they are called SNPs. Besides alleles, there are also other in-between single-nucleotides in the gene, but these are the same for the whole population of a given (e.g. human) genome. True? $\endgroup$ – user2340939 Feb 17 '19 at 19:48
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The definition of allele depends on the context.

If you look at the DNA of a single person you have usually two copies of each autosomal chromosomes. Each copy is called an allele. If you know look at the sequence at a specific position, you can say one of the two bases are located at one allele and the other base on the other allele.

Beside this there is a definition of allele if you take a look at a many persons or a whole population. Here you call an allele "as alternative forms of a particular sequence".

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  • $\begingroup$ But how is SNP, which indicates a single nucleotide, associated with a major and minor allele, since either one can be of length greater than on? Does it mean that starting from the specific SNP position, it can either be the start of the major or the minor allele? $\endgroup$ – user2340939 Dec 8 '19 at 18:03
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From what I could find the .gen file format for SNPs was developed for the IMPUTE2 program and is generally meant to be a flexible file format for SNP data. The description of the file format is supposed to documented here (multiple pages pointing to that link), sadly that link is broken / the site is removed. However, I found some other descriptions of the format:

In the GEN format each SNP is represented as a set of three probabilities which correspond to the allele pairs AA,AB,BB.

from here

The genfile contains predictor values, one row per predictor.
--gen-skip indicates how many header rows (typically 0 or 1);
--gen-headers indicates how many header columns (typically 0 to 5).
--gen-probs should be 0, 1, 2, 3 or 4:
0 - haplotypes - predictor values should be "0 0", "0 1", "1 0" or "1 1"
1 - dosages - predictors provide the (expected) number of A alleles
2 - two probs - providing probability of being AA or AB
3 - three probs - providing probabilities of being AA, AB or BB
4 - four probs - providing probabilties of being AA, AB, BB or NA, where A and B are the A1 and A2 alleles

from here

Like finswimmer already wrote in his answer, it is very important to be clear about what is considered an allele in the context of SNPs. For the .gen file format this is the identity of the base at a given (SNP) position and since humans have a diploid genome, the allele of a specific individual can be one of three versions (usually called AA, AB & BB).

Regarding your specific points:

Since each SNP has associated allele A and allele B, I assume that the file only contains Causative SNPs, and not Linked SNPs, since the former reside in the gene, and the later don't. Since each SNP in the file has an associated gene (actually genotype, some combination of allele A and B). Correct?

  • The alleles in the .gen file refer to the respective SNPs not genes.
  • There is no reason to assume that an given .gen file only contains certain SNPs; if it does this is not due to the data format.
  • The SNPs in a .gen file do not generally have to be linked to a gene.
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  • $\begingroup$ I've added example, can you comment on it and answer the remaining of my questions? $\endgroup$ – user2340939 Jan 7 at 23:10

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