Autosomal recessive logic

SNP Haplotyper Autosomal Recessive Logic

The table below shows the effect of the filtering strategy for Autosomal Recessive cases. The top grid shows the 27 possible combinations of SNPs between the child reference, male_partner, and female_partner. Note that fFFor autosomal recessive cases both partners are carriers. 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 are assigned as ▇ low_risk or ▇ high_risk for AB SNP sites in the embryo depending on whether the reference is affected or unaffected. Additionally, for autosomal recessive cases, the risk is allocated to being associated with an allele either inherited from the male_partner ♂ or the female_partner♀.

An extra filtering steps occurs for consanguineous cases - these are filtered the same way as for affected references (and the reference will always be affected), but due to the limited number of informative SNPs normally present two additional criteria are used which identify high risk SNPs normally ignored. It is impossible to assign this risk as associated with the female partner, or male partner, so these are labelled as inherited from both_partner ⚤.

Autosomal Recessive:

reference

AA

BB

AB

Male partner

AA

BB

AB

AA

BB

AB

AA

BB

AB

Female 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 calls where both partners are homozygous

reference

AA

BB

AB

Male partner

AA

BB

AB

AA

BB

AB

AA

BB

AB

Female 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 calls where all three of the trio are heterozygous

reference

AA

BB

AB

Male partner

AA

BB

AB

AA

BB

AB

AA

BB

AB

Female 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 calls where all three of the trio are different from one another

reference

AA

BB

AB

Male partner

AA

BB

AB

AA

BB

AB

AA

BB

AB

Female 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

AR1

AR2

AR3

AR4

AR5

AR6

AR7

AR8

AR9

AR10

Affected child reference

♀

♂

♀

♂

♀

♂

Unaffected child reference

♀

♂

♀

♂

♀

♂

embryo

AB

AA

AB

BB

AB

Consanguineous

♀

♂

⚤

♀

♂

⚤

♀

♂

We have four criteria which are used to classify the remaining SNPs AR1, AR2, AR3, and AR4. The ID codes for these criteria are referenced in the codebase so that the functions performing these steps can be identified:

Criteria_AR1

If child reference is AA, Male Partner Carrier AA, and Female Partner Carrier is AB depending on the child reference's status we can classify the SNPs as:

For Affected reference SNP is Low_risk from female partner: As the child reference is Affected this indicates that A is associated with the autosomal recessive condition as the child is homozygous for AA. We can therefore classify the SNP in AB embryos as low_risk as the B must be inherited from the female partner.
For Unaffected reference SNP is High_risk from female partner: As the child reference is Unaffected this indicates that A is NOT associated with the autosomal recessive condition as the child is homozygous for AA. We can therefore classify the SNP in AB embryos as High_risk with the B inherited from the female carrier partner.(Consanguineous)

Criteria_AR2

If child reference is AA, Male Partner Carrier AB, and Female Partner Carrier is AA depending on the child reference's status we can classify the SNPs as:

For Affected reference SNP is Low_risk from male partner: As the child reference is Affected this indicates that A is associated with the autosomal recessive condition as the child is homozygous for AA. We can therefore classify the SNP in AB embryos as low_risk as the B must be inherited from the male partner.
For Unaffected reference SNP is High_risk from male partner: As the child reference is Unaffected this indicates that A is NOT associated with the autosomal recessive condition as the child is homozygous for AA. We can therefore classify the SNP in AB embryos as High_risk with the B inherited from the male carrier partner.

Criteria_AR3 (Consanguineous only)

If the affected child reference is AA, Male Partner Carrier AB, and Female Partner Carrier is AB we can classify the SNPs as:

Affected reference (Consanguineous) As the child reference is Affected this indicates that A is associated with the autosomal recessive condition as the child is homozygous for AA. We can therefore classify the SNP in AA embryos as High_risk as an A must be inherited from the each partner.

Criteria_AR4

If child reference is BB, Male Partner Carrier BB, and Female Partner Carrier is AB depending on the child reference's status we can classify the SNPs as:

For Affected reference SNP is Low_risk from female partner: As the child reference is Affected this indicates that B is associated with the autosomal recessive condition as the child is homozygous for BB. We can therefore classify the SNP in AB embryos as low_risk as the A must be inherited from the female partner.
For Unaffected reference SNP is High_risk from female partner: As the child reference is Unaffected this indicates that B is NOT associated with the autosomal recessive condition as the child is homozygous for BB. We can therefore classify the SNP in AB embryos as High_risk with the A inherited from the female carrier partner.

Criteria_AR5

If child reference is BB, Male Partner Carrier AB, and Female Partner Carrier is BB depending on the child reference's status we can classify the SNPs as:

For Affected reference including when (Consanguineous) SNP is Low_risk from male partner: As the child reference is Affected this indicates that B is associated with the autosomal recessive condition as the child is homozygous for BB. We can therefore classify the SNP in AB embryos as low_risk as the A must be inherited from the male partner.
For Unaffected reference SNP is High_risk from male partner: As the child reference is Unaffected this indicates that B is NOT associated with the autosomal recessive condition as the child is homozygous for BB. We can therefore classify the SNP in AB embryos as High_risk with the A inherited from the male carrier partner.

Criteria_AR6 (Consanguineous only)

If the affected child reference is BB, Male Partner Carrier AB, and Female Partner Carrier is AB we can classify the SNPs as:

Affected reference (Consanguineous) As the child reference is Affected this indicates that B is associated with the autosomal recessive condition as the child is homozygous for BB. We can therefore classify the SNP in BB embryos as High_risk as a B must be inherited from the each partner.

Criteria_AR7

If child reference is AB, Male Partner Carrier AA, and Female Partner Carrier is AB depending on the child reference's status we can classify the SNPs as:

For Affected reference SNP is High_risk from female partner: As the child reference is Affected this indicates that B from the female partner is associated with the autosomal recessive condition. We can therefore classify the SNP in AB embryos as High_risk as the B must be inherited from the female partner.
For Unaffected reference SNP is low_risk from female partner: As the child reference is Unaffected this indicates that B from the female partner is NOT associated with the autosomal recessive condition. We can therefore classify the SNP in AB embryos as Low_risk as the B must be inherited from the female partner

Criteria_AR8

If child reference is AB, Male Partner Carrier BB, and Female Partner Carrier is AB depending on the child reference's status we can classify the SNPs as:

For Affected reference SNP is High_risk from female partner: As the child reference is Affected this indicates that A from the female partner is associated with the autosomal recessive condition. We can therefore classify the SNP in AB embryos as High_risk as the A must be inherited from the female partner.
For Unaffected reference SNP is low_risk from female partner: As the child reference is Unaffected this indicates that A from the female partner is NOT associated with the autosomal recessive condition. We can therefore classify the SNP in AB embryos as Low_risk as the A must be inherited from the female partner

Criteria_AR9

If child reference is AB, Male Partner Carrier AB, and Female Partner Carrier is AA depending on the child reference's status we can classify the SNPs as:

For Affected reference

SNP is High_risk from male partner: As the child reference is Affected this indicates that B from the male partner is associated with the autosomal recessive condition. We can therefore classify the SNP in AB embryos as High_risk as the B must be inherited from the male partner.

For Unaffected reference SNP is low_risk from female partner: As the child reference is Unaffected this indicates that B from the male partner is NOT associated with the autosomal recessive condition. We can therefore classify the SNP in AB embryos as Low_risk as the B must be inherited from the male partner

Criteria_AR10

If child reference is AB, Male Partner Carrier AB, and Female Partner Carrier is BB depending on the child reference's status we can classify the SNPs as:

For Affected reference SNP is High_risk from male partner: As the child reference is Affected this indicates that A from the male partner is associated with the autosomal recessive condition. We can therefore classify the SNP in AB embryos as High_risk as the A must be inherited from the male partner.
For Unaffected reference SNP is low_risk from male partner: As the child reference is Unaffected this indicates that A from the male partner is NOT associated with the autosomal recessive condition. We can therefore classify the SNP in AB embryos as Low_risk as the A must be inherited from the male partner