Autosomal dominant logic

SNP Haplotyper Autosomal Dominant Logic

The table below shows the effect of the filtering strategy for Autosomal Dominant cases where the reference is a grandparent. The top grid shows the 27 possible combinations of SNPs between the reference, affected_partner, and unaffected_partner. Subsequent grids show the effects of each stage of the filtering strategy. The blocks coloured ▇ are uninformative SNPs and are filtered from the data set to leave informative SNPs ▇.

The final grid shows how the SNPs would be assigned as ▇ low_risk SNPs or ▇ high_risk SNPs depending upon whether the reference was affected or unaffected.

If reference is a grandparent:

Autosomal Dominant:

reference

AA

BB

AB

Affected partner

AA

BB

AB

AA

BB

AB

AA

BB

AB

Unaffected partner

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

Show only homozygous SNPs for reference

reference

AA

BB

AB

Affected partner

AA

BB

AB

AA

BB

AB

AA

BB

AB

Unaffected partner

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

Show only homozygous SNPs for unaffected partner

reference

AA

BB

AB

Affected partner

AA

BB

AB

AA

BB

AB

AA

BB

AB

Unaffected partner

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

Show only heterozygous SNPs for affected partner

reference

AA

BB

AB

Affected partner

AA

BB

AB

AA

BB

AB

AA

BB

AB

Unaffected partner

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

For embryo with AB, then we can categorise the SNP as high_risk or low_risk:

embryo

AB

Criteria

AD3

AD1

AD2

AD4

Affected reference

Unaffected reference

We have four criteria which are used to classify the remaining SNPs AD1, AD2, AD3, and AD4. The ID codes for these criteria are referenced in the codebase so that the functions performing these steps can be identified:

If reference = “grandparent”:

For an Affected reference (grandparent):

Criteria_AD1 + Option_AD1 :

The affected reference is AA and the affected partner is AB:

Hence the A allele must be associated with the Autosomal Dominant condition.

The unaffected partner is BB and the affected partner is AB:

Hence if the embryo is AB then the B must be inherited from the unaffected partner, BB. By a process of elimination this means the A was inherited from the affected partner. Therefore category = High_risk

Criteria_AD2 + Option_AD2:

The affected reference is BB and the affected partner is AB:

Hence the B allele must be associated with the Autosomal Dominant condition.

The unaffected partner is AA and the affected partner is AB:

Hence if the embryo is AB then the A must be inherited from the unaffected partner, AA. By a process of elimination this means the B was inherited from the affected partner. Therefore category = High_risk

Criteria_AD3 + Option_AD3:

The affected reference is AA and the affected partner is AB:

Hence the A allele must be associated with the Autosomal Dominant condition.

The unaffected partner is AA and the affected partner is AB:

Hence if the embryo is AB then the A must be inherited from the unaffected partner, AA. By a process of elimination this means the B was inherited from the affected partner. Therefore category = Low_risk

Criteria_AD4 + Option_AD4:

The affected reference is BB and the affected partner is AB:

Hence the B allele must be associated with the Autosomal Dominant condition.

The unaffected partner is BB and the affected partner is AB:

Hence if the embryo is AB then the B must be inherited from the unaffected partner, BB. By a process of elimination this means the A was inherited from the affected partner. Therefore category = Low_risk

If an unaffected reference is used then all the inferences are reversed as described below:

For an Unaffected reference (grandparent):

Criteria_AD1 + Option_AD5:

The unaffected reference is AA and the affected partner is AB:

Hence the B allele must be associated with the Autosomal Dominant condition.

The unaffected partner is BB and the affected partner is AB:

Hence if the embryo is AB then the B must be inherited from the unaffected partner, BB. By a process of elimination this means the A was inherited from the affected partner. Therefore category = Low_risk

Criteria_AD + Option_AD6:

The unaffected reference is BB and the affected partner is AB:

Hence the A allele must be associated with the Autosomal Dominant condition.

The unaffected partner is AA and the affected partner is AB:

Hence if the embryo is AB then the A must be inherited from the unaffected partner, AA. By a process of elimination this means the B was inherited from the affected partner. Therefore category = Low_risk

Criteria_AD3 + Option_AD7:

The unaffected reference is AA and the affected partner is AB:

Hence the B allele must be associated with the Autosomal Dominant condition.

The unaffected partner is AA and the affected partner is AB:

Hence if the embryo is AB then the A must be inherited from the unaffected partner, AA. By a process of elimination this means the B was inherited from the affected partner. Therefore category = High_risk

Criteria_AD4 + Option_AD8:

The unaffected reference is BB and the affected partner is AB:

Hence the A allele must be associated with the Autosomal Dominant condition.

The unaffected partner is BB and the affected partner is AB:

Hence if the embryo is AB then the B must be inherited from the unaffected partner, BB. By a process of elimination this means the A was inherited from the affected partner. Therefore category = High_risk

The table below shows the effect of the filtering strategy for Autosomal Dominant cases where the reference is a child/embryo. The top grid shows the 27 possible combinations of SNPs between the reference, affected_partner, and unaffected_partner. Subsequent grids show the effects of each stage of the filtering strategy. The blocks coloured ▇ are uninformative SNPs and are filtered from the data set to leave informative SNPs ▇.

The final grid shows how the SNPs would be assigned as ▇ low_risk SNPs or ▇ high_risk SNPs depending upon whether the reference was affected or unaffected.

If reference is a child/embryo:

Autosomal Dominant:

reference

AA

BB

AB

Affected partner

AA

BB

AB

AA

BB

AB

AA

BB

AB

Unaffected partner

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

Show only heterozygous SNPs for affected partner

reference

AA

BB

AB

Affected partner

AA

BB

AB

AA

BB

AB

AA

BB

AB

Unaffected partner

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

Show only homozygous SNPs for unaffected partner

reference

AA

BB

AB

Affected partner

AA

BB

AB

AA

BB

AB

AA

BB

AB

Unaffected partner

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

FILTER OUT SNPs were the reference and unaffected_partner are homozygous for different SNPS

reference

AA

BB

AB

Affected partner

AA

BB

AB

AA

BB

AB

AA

BB

AB

Unaffected partner

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

AA

BB

AB

For embryo reference is a grandparent:o with AB, then we can categorise the SNP as high_risk or low_risk:

embryo

AB

Criteria

AD7

AD8

AD5

AD6

Affected reference

Unaffected reference

If reference = “child”:

For an Affected reference (child):

Criteria_AD5 + Option_AD9:

The affected reference is AB and the affected partner is AB and the unaffected partner is AA :

Hence the B allele must be associated with the Autosomal Dominant condition as the reference is a child of both partners and must have inherited the A from the unaffected partner, AA.

The unaffected partner is AA and the affected partner is AB:

Hence if the embryo is AB then the A must be inherited from the unaffected partner, AA. By a process of elimination this means the B was inherited from the affected partner. Therefore category = High_risk

Criteria_AD6 + Option_AD10:

The affected reference is AB and the affected partner is AB and the unaffected partner is BB :

Hence the A allele must be associated with the Autosomal Dominant condition as the reference is a child of both partners and must have inherited the B from the unaffected partner, BB.

The unaffected partner is BB and the affected partner is AB:

Hence if the embryo is AB then the B must be inherited from the unaffected partner, BB. By a process of elimination this means the A was inherited from the affected partner. Therefore category = High_risk

Criteria_AD7 + Option_AD11:

The affected reference is AA and the affected partner is AB :

Hence the A allele must be associated with the Autosomal Dominant condition.

The unaffected partner is AA and the affected partner is AB:

Hence if the embryo is AB then the A must be inherited from the unaffected partner, AA. By a process of elimination this means the B was inherited from the affected partner. Therefore category = Low_risk

Criteria_AD8 + Option_AD12:

The affected reference is BB and the affected partner is AB :

Hence the B allele must be associated with the Autosomal Dominant condition.

The unaffected partner is BB and the affected partner is AB:

Hence if the embryo is AB then the B must be inherited from the unaffected partner, BB. By a process of elimination this means the A was inherited from the affected partner. Therefore category = Low_risk

If an unaffected reference is used then all the inferences are reversed as described below:

For an Unaffected reference (child):

Criteria_AD5 + Option_AD13:

The unaffected reference is AB and the affected partner is AB and the unaffected partner is AA :

Hence the A allele must be associated with the Autosomal Dominant condition as the reference is a child of both partners and must have inherited the B from the affected partner, AB.

The unaffected partner is AA and the affected partner is AB:

Hence if the embryo is AB then the A must be inherited from the unaffected partner, AA and the B was inherited from the affected partner. Therefore category = Low_risk

Criteria_AD6 + Option_AD14:

The unaffected reference is AB and the affected partner is AB and the unaffected partner is BB :

Hence the B allele must be associated with the Autosomal Dominant condition as the reference is a child of both partners and must have inherited the A from the affected partner, AB.

The unaffected partner is BB and the affected partner is AB:

Hence if the embryo is AB then the B must be inherited from the unaffected partner, BB and the A was inherited from the affected partner. Therefore category = Low_risk

Criteria_AD7 + Option_AD15:

The unaffected reference is AA and the affected partner is AB :

Hence the B allele must be associated with the Autosomal Dominant condition.

The unaffected partner is AA and the affected partner is AB:

Hence if the embryo is AB then the A must be inherited from the unaffected partner, AA and the B was inherited from the affected partner. Therefore category = High_risk

Criteria_AD8 + Option_AD16:

The unaffected reference is BB and the affected partner is AB:

Hence the A allele must be associated with the Autosomal Dominant condition.

The unaffected partner is BB and the affected partner is AB:

Hence if the embryo is AB then the B must be inherited from the unaffected partner, BB and the A was inherited from the affected partner. Therefore category = High_risk