- Genotyping technologies, homozygotes and hemizygotes.
Depending on the organism, chromosome and position where a SNP is
located, it can have different genotypes. In particular, alleles may be present
in a different number of copies that have to be handled in different ways. For
example, SNPs in the human Y chromosome will have hemizygous
genotypes, with only four possible states ("A", "T", "C" and "G"), whereas SNPs in autosomes can be homozygous or heterozygous.
Most of the extant genotyping technologies are not able to ascertain the
number of copies of alleles from a given SNP present in a given sample. That
is, samples with genotypes "AA" and "A" are going to give the same results,
making it impossible to distinguish an homozygous from a hemizygous
This is not usually a problem, since most SNPs are located in the autosomes
and, thus, the corresponding genotypes will always be either homozygous or
However, given that SNPator does not force the user to provide information
about the location of the selected SNPs or about the sex of the samples, this
may result in ambiguities.
An ambiguity is produced when undefined genotypes (whose homo- or
hemizygous state is not known) are uploaded into SNPator. These
ambiguities pose a threat to the reliability of the results and cannot be solved
without information of the nature of the SNPs and Samples involved.
The Genotypes Validation section has been developed to tackle this
All analysis and calculations in SNPator are prepared to work with both
haploid and diploid data. In the case of humans, that means mostly working
with homozygous and heterozygous data for the autosomes and also with
hemizygous data for the sex chromosomes (excepting the pseudoatosomic
region of the Y chromosome).
Lets imagine a SNP with "A" and "T" variants. The possible results are coded
in SNPator using the following convention:
AA means stands for an individual homozygous for allele A
TT means stands for an individual homozygous for allele T
AT means stands for an heterozygous individual
A means stands for an individual hemizygous for allele A
T means stands for an individual hemizygous for allele T
When Genotypes are uploaded into SNPator, they are flagged as not
validated by default. In such situation, it is not allowed to perform analysis
upon these data, although the user can download and modify data at will.
By performing the Genotypes Validation procedure, any ambiguous results will be assigned their proper values according to the instructions of the user.
After validation genotypes will be flagged as validated and it will be possible
to work with all the analysis tools in SNPator .
Whenever you select a Study in the Study selection option, if it contains not
validated data, you will be taken to a webform where you can perform the Genotypes Validation.
Since you may not have the required information to validate your results (sex
of samples and location of SNPs) and/or you need to upload SNPs data into SNPator before validation, you will be able to select the study anyway and
delay the Validation procedure. If you choose to do so, once inside the study
you will be able to add, modify and download data, but you will not be allowed
to perform any kind of analysis. Whenever you feel like validating your data
you can go back to the Genotypes Validation section.
The information you need is basically the number of copies of the SNPs you
are working with.
In the most usual situation, when all the SNPs in a Study belong to
autosomes , you will only have to tell it to SNPator using the appropriate
option and all the validation process will proceed automatically.
The same situation comes when all the SNPs belong to chomosome Y or to a
If you have SNPs from mixed genomic locations in your study (for example
SNPs from autosomes and the Y chromosome), you will have to specify the
origin of each one in order to perform the validation.
You can do it manually, of course, but the quickest way is to let SNPator to fill
the chromosome and position information from the dbSNP database using
the Load dbSNP info section.
In case you are working with SNPs located in the X chromosome, you will
have to provide information about the sex of the samples involved, to
distinguish homozygous women (AA) from hemizygous men (A).
Finally, in order to cover the most complex situations (pseudoautosomal
region in Y chromosome, for example), manual validation, by SNP or by
result is also possible.