Pedigree Format

Column Name Content
FamilyID Family identifier
BRCA1carrier BRCA1 carrier status (NA=unknown, 0=confirmed normal, 1=confirmed carrier)
BRCA2carrier BRCA2 carrier status ( NA=unknown,0=confirmed normal, 1=confirmed carrier)
ID Member identifier
Gender Gender (0=female, 1=male)
FatherID Father’s identifier number
MotherID Mother’s identifier number
AffectedBreast Breast cancer status (0=no cancer, 1=breast cancer, one breast involved; 2=bilateral breast cancer, NA=unknown status)
AffectedOvary Ovarian cancer status (0=no cancer, 1=ovarian cancer, NA=unknown status)
AgeBreast Age of onset of breast cancer if a breast cancer case.Current age or age of death if not a breast cancer case.NA if there is no age information
AgeOvary Age of onset of ovarian cancer if an ovarian cancer case. Current age or age of death if not an ovarian cancer case.NA if there is no age information
AgeBreastContralateral Age at onset of breast cancer, second breast.Only for members with breast cancer status=2. For the rest enter a 0.
Twins Identifies siblings who are identical twins. Enter 0 for everyone. Functionality to handle twins will be developed in future.
ethnic Identifies the ethnicity of each family member.Enter “nonAJ”, “AJ”, “Italian”, “Other” or NA (as recognized by is.na() function).

Example Pedigree Data

FamilyID BRCA1carrier BRCA2carrier ID Gender FatherID MotherID AffectedBreast AffectedOvary AgeBreast AgeOvary AgeBreastContralateral Twins ethnic
1 0 1 1 0 3 2 1 0 43 44 0 0 nonAJ
1 0 NA 2 0 11 10 1 0 28 53 0 0 nonAJ
1 0 NA 3 1 13 12 0 0 67 67 0 0 nonAJ
1 0 NA 4 0 21 1 0 0 15 15 0 0 nonAJ
1 0 NA 5 0 21 1 0 0 18 18 0 0 nonAJ
1 0 NA 6 1 21 1 0 0 13 13 0 0 nonAJ
1 0 NA 7 1 3 2 0 0 40 40 0 0 nonAJ
1 0 NA 8 0 3 2 0 0 41 41 0 0 nonAJ
1 0 NA 9 0 3 2 0 0 37 37 0 0 nonAJ
1 0 NA 10 0 0 0 0 0 77 77 0 0 nonAJ
1 0 NA 11 1 0 0 0 0 55 55 0 0 nonAJ
1 0 NA 12 0 0 0 0 0 93 93 0 0 nonAJ
1 0 NA 13 1 0 0 0 0 82 82 0 0 nonAJ
1 0 NA 14 0 11 10 0 0 9 9 0 0 nonAJ
1 0 NA 15 0 11 10 2 0 44 44 44 0 nonAJ
1 0 NA 16 0 11 10 0 0 53 53 0 0 nonAJ
1 0 NA 17 0 13 12 0 0 70 70 0 0 nonAJ
1 0 NA 18 0 13 12 0 0 61 61 0 0 nonAJ
1 0 NA 19 1 13 12 0 0 73 73 0 0 nonAJ
1 0 NA 20 1 13 12 0 0 55 55 0 0 nonAJ
1 0 NA 21 1 0 0 0 0 47 47 0 0 nonAJ

Calling Famdenovo.BRCA

Famdenovo.BRCA() takes three inputs:

Famdenovo.BRCA(sample_fam,denovo_ratio1 = .15, denovo_ratio2 = .15)
## 1
##      FamilyID ID  gene                denovo_probability   
## [1,] "1"      "1" "BRCA2_denovo_prob" "0.00290900643776915"

For this sample family, the one carrier, ID = 1, has a BRCA2 mutation. This mutation is not predicted to be de novo, with a probability of 0.0029

De novo Example

Here we make a few changes to the pedigree, to make it a de novo example. We do this by making the earlier generations less likely to carry mutation, and later generations more likely. We also change ID 4 to a BRCA2 carrier as an additional example of a familial mutation.

## 1
##      FamilyID ID  gene                denovo_probability   
## [1,] "1"      "1" "BRCA2_denovo_prob" "0.510266530753294"  
## [2,] "1"      "4" "BRCA2_denovo_prob" "0.00720349698443668"

Now, both ID = 1 and 4 have BRCA2 mutations. For ID = 4, as we would expect, the mutation is not predicted to be de novo with a probability of 0.007. ID = 1 is predicted to be de novo, with a probability of 0.510.