X-linked logic
SNP Haplotyper X-Linked Logic
The table below shows the effect of the filtering strategy for X Linked cases where the reference is a carrier grandmother or affected child. The top grid shows the 18 possible combinations of SNPs between the reference, affected_partner, and unaffected_partner (NOTE: 18 rather than 27 because for X-linked cases the male unaffected is hemizygous and AB will only occur due to miscalls). 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 Female AB, Male AA, or Male BB.
NOTE: The input files do not distinguish between hemizygous (A, B) and heterozygous/homozygous (AA, BB) alleles. For male unaffected partner and male child affected reference AA = A & BB = B, a reading of AB indicates a miscall.
Logic is the same whether the reference is a carrier grandparent or affected child.
X Linked: | ||||||||||||||||||
Affected/Carrier Reference | AA | AA | AA | AA | AA | AA | BB | BB | BB | BB | BB | BB | AB | AB | AB | AB | AB | AB |
Carrier Female partner | AA | AA | BB | BB | AB | AB | AA | AA | BB | BB | AB | AB | AA | AA | BB | BB | AB | AB |
Unaffected Male partner (Hemizygous) | AA | BB | AA | BB | AA | BB | AA | BB | AA | BB | AA | BB | AA | BB | AA | BB | AA | BB |
Show only homozygous SNPs for carrier/affected reference (Note that for an affected child the first filtering step would remove ~ 0 SNPs as this male affected child reference would be hemizygous and AB would only occur due to miscalls). | ||||||||||||||||||
Affected/Carrier Reference | AA | AA | AA | AA | AA | AA | BB | BB | BB | BB | BB | BB | AB | AB | AB | AB | AB | AB |
Carrier Female partner | AA | AA | BB | BB | AB | AB | AA | AA | BB | BB | AB | AB | AA | AA | BB | BB | AB | AB |
Unaffected Male partner (Hemizygous) | AA | BB | AA | BB | AA | BB | AA | BB | AA | BB | AA | BB | AA | BB | AA | BB | AA | BB |
Show only heterozygous SNPs for carrier partner | ||||||||||||||||||
Affected/Carrier Reference | AA | AA | AA | AA | AA | AA | BB | BB | BB | BB | BB | BB | AB | AB | AB | AB | AB | AB |
Carrier Female partner | AA | AA | BB | BB | AB | AB | AA | AA | BB | BB | AB | AB | AA | AA | BB | BB | AB | AB |
Unaffected Male partner (Hemizygous) | AA | BB | AA | BB | AA | BB | AA | BB | AA | BB | AA | BB | AA | BB | AA | BB | AA | BB |
IF EMBRYO FEMALE: | ||||||||||||||||||
For FEMALE embryo with AB, then we can categorise the SNP as high_risk or low_risk: | ||||||||||||||||||
FEMALE embryo | AB | AB | AB | AB | ||||||||||||||
Criteria | XL1 | XL2 | XL3 | XL4 | ||||||||||||||
IF EMBRYO MALE: | ||||||||||||||||||
Filter out same homozygous in carrier reference and Male unaffected partner (AA_AA and BB_BB) | ||||||||||||||||||
Affected/Carrier Reference | AA | AA | AA | AA | AA | AA | BB | BB | BB | BB | BB | BB | AB | AB | AB | AB | AB | AB |
Carrier Female partner | AA | AA | BB | BB | AB | AB | AA | AA | BB | BB | AB | AB | AA | AA | BB | BB | AB | AB |
Unaffected Male partner (Hemizygous) | AA | BB | AA | BB | AA | BB | AA | BB | AA | BB | AA | BB | AA | BB | AA | BB | AA | BB |
For MALE embryo with AA, then we can categorise the SNP as high_risk or low_risk: | ||||||||||||||||||
MALE embryo | AA | AA | AA | AA | ||||||||||||||
Criteria | XL5 | XL6 | ||||||||||||||||
For MALE embryo with BB, then we can categorise the SNP as high_risk or low_risk: | ||||||||||||||||||
MALE embryo | BB | BB | BB | BB | ||||||||||||||
Criteria | XL7 | XL8 | ||||||||||||||||
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:
- For a FEMALE embryo
- Criteria_XL1 :
- The carrier/affected reference is AA and the carrier female partner is AB:
- Hence the A allele must be associated with the X-linked condition.
- The unaffected male partner is AA (actually hemizygous A) and the carrier female partner is AB:
- Hence if the female 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 unaffected male partner. Therefore category = Low_risk
- Criteria_XL2:
- The carrier/affected reference is AA and the carrier female partner is AB:
- Hence the A allele must be associated with the X-linked condition.
- The unaffected male partner is BB (actually hemizygous B) and the carrier female partner is AB:
- Hence if the female 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 carrier female partner. Therefore category = High_risk
- Criteria_XL3:
- The carrier/affected reference is BB and the carrier female partner is AB:
- Hence the B allele must be associated with the X-linked condition.
- The unaffected male partner is AA (actually hemizygous A) and the carrier female partner is AB:
- Hence if the female embryo is AB then the B must be inherited from the female carrier partner, AB. By a process of elimination this means the A was inherited from the unaffected male partner. Therefore category = High_risk
- Criteria_XL4:
- The carrier/affected reference is BB and the carrier female partner is AB:
- Hence the B allele must be associated with the X-linked condition.
- The unaffected male partner is BB (actually hemizygous B) and the carrier female partner is AB:
- Hence if the female 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 carrier female partner. Therefore category = Low_risk
- For a MALE embryo:
- Criteria_XL5:
- If the MALE EMBRYO is AA (Hemizygous A):
- The Affected/Carrier reference is AA and the female carrier partner is AB:
- Hence the A allele must be associated with the X-linked condition as this is the common allele between the two.
- The unaffected male partner does not contribute any X-linked genes to a male embryo so can me ignored:
- Hence if the embryo is AA (Hemizygous A) then the A must be inherited from the female carrier partner, AB. Therefore category = High_risk
- Criteria_XL6:
- If the MALE EMBRYO is AA (Hemizygous A):
- The Affected/Carrier reference is BB and the female carrier partner is AB:
- Hence the B allele must be associated with the X-linked condition as this is the common allele between the two.
- The unaffected male partner does not contribute any X-linked genes to a male embryo so can me ignored:
- Hence if the embryo is AA (Hemizygous A) then the A must be inherited from the female carrier partner, AB. Therefore category = Low_risk
- Criteria_XL7:
- If the MALE EMBRYO is BB (Hemizygous B):
- The Affected/Carrier reference is AA and the female carrier partner is AB:
- Hence the A allele must be associated with the X-linked condition as this is the common allele between the two.
- The unaffected male partner does not contribute any X-linked genes to a male embryo so can me ignored:
- Hence if the embryo is BB (Hemizygous B) then the B must be inherited from the female carrier partner, AB. Therefore category = Low_risk
- Criteria_XL8:
- If the MALE EMBRYO is BB (Hemizygous B):
- The Affected/Carrier reference is BB and the female carrier partner is AB:
- Hence the B allele must be associated with the X-linked condition as this is the common allele between the two.
- The unaffected male partner does not contribute any X-linked genes to a male embryo so can me ignored:
- Hence if the embryo is BB (Hemizygous B) then the B must be inherited from the female carrier partner, AB. Therefore category = High_risk