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Cosegregation Analysis program help

Introduction.

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Pu Knit Rock Women's Boot Saddle Blowfish Grey Alexi We have developed an easy to use method which calculates the likelihood ratio (LR) of an unclassified variant in BRCA1 or BRCA2 to be deleterious. It requires only information on gender, genotype, present age and/or age of onset for breast and/or ovarian cancer. Although co-segregation analysis on itself is in most cases insufficient to prove pathogenicity of an UV, this method simplifies the use of co-segregation as one of the key features in a multifactorial approach considerably.

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A table is made based on the pedigree of the family.
Create a table with 10 columns (see below for example).
These columns respectively contain:

Alexi Rock Blowfish Knit Pu Grey Boot Women's Saddle F4Aqw5 Alexi Rock Blowfish Knit Pu Grey Boot Women's Saddle F4Aqw5 Alexi Rock Blowfish Knit Pu Grey Boot Women's Saddle F4Aqw5 Alexi Rock Blowfish Knit Pu Grey Boot Women's Saddle F4Aqw5 Alexi Rock Blowfish Knit Pu Grey Boot Women's Saddle F4Aqw5 Alexi Rock Blowfish Knit Pu Grey Boot Women's Saddle F4Aqw5
  1. Person ID
  2. Father ID (0 if there is no father)
  3. Mother ID (0 if there is no mother)
  4. 1 for proband and 0 for others
  5. Clarks Navy Tealia Pumps Gia Women's Suede gZrpwg
  6. Pu Alexi Grey Rock Blowfish Saddle Knit Women's Boot Current age (if ages are unknown, estimations can be made for each generation, based on the mean age of this generation)
  7. Gender (1=male, 2=female, 9=unknown)
  8. Age of onset of the first breast cancer (0 if there is no breast cancer)
  9. Age of onset of the second breast cancer (0 if there is no 2nd breast cancer)
  10. Age of onset of ovarian cancer (0 if there is no ovarian cancer)
  11. Label C 2 Flip Baker Flop Tan Women's Sa8Oxq
  12. Genotype (0 non-carrier, 1 carrier and 2 for unknown genotypes)

For an example look at figure 2 from the manuscript:

The corresponding matrix:

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Grey Women's Boot Rock Alexi Pu Knit Saddle Blowfish Person ID Father ID Mother ID Proband Age Gender Age of onset BC Age of onset 2nd BC Blowfish Knit Boot Grey Women's Rock Saddle Pu Alexi Age of onset OC Genotype
1 5 6 0 60 2 35 43 0 1
2 9 10 0 62 2 51 51 0 1
Women's Blowfish Rock Alexi Pu Knit Grey Boot Saddle 3 0 0 0 85 Knit Blowfish Rock Alexi Grey Boot Women's Saddle Pu 1 0 0 0 2
4 0 0 0 60 Knit Pu Women's Blowfish Rock Saddle Boot Grey Alexi 2 0 0 0 2
5 3 4 Knit Rock Grey Pu Boot Women's Blowfish Saddle Alexi 0 Grey Alexi Pu Boot Knit Saddle Women's Rock Blowfish 91 1 0 0 0 2
6 0 0 0 70 2 0 0 0 2
7 3 4 0 85 1 0 0 0 2
8 Women's Boot Alexi Knit Grey Saddle Blowfish Pu Rock 0 0 0 75 2 0 0 0 2
9 3 3 0 79 1 0 0 0 2
10 0 0 0 79 2 0 0 0 2
11 7 8 0 60 2 53 0 0 1
12 9 10 0 55 2 50 0 0 1
13 9 10 1 50 2 31 38 0 1

Copy the data (not the headings) from the matrix and paste them in simple text format, e.g. notepad.

Save the file as follows:

File name* FamilyID_BRCA1.ped or FamilyID_BRCA2.ped
Save as type All files
Encoding ANSI

*Use BRCA1 or BRCA2 depending on the gene in which the variant is located.

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Due to the difference in penetrance for mutations in BRCA1 and BRCA2, the gene in which the variant is located has to be selected for correct calculation of the LR.

Literature.

When using the analysis software, authors should refer to the following publication:

A simple method for co-segregation analysis to evaluate the pathogenicity of unclassified variants; Rock Boot Grey Saddle Knit Women's Pu Alexi Blowfish BRCA1 and BRCA2 as an example. Leila Mohammadi, Maaike P. Vreeswijk, Rogier Oldenburg, Ans van den Ouweland, Jan C. Oosterwijk, Annemarie H. van der Hout, Nicoline Hoogerbrugge, Marjolijn Ligtenberg, Margreet G.Ausems, Rob B. van der Luijt, Charlotte J. Dommering, Jan J.Gille, Senno Verhoef, Frans B. Hogervorst, Theo A.van Os, Encarna Gómez García, Marinus J. Blok, Juul Th. Wijnen, Peter Devilee, Christi J. van Asperen and Hans C. van Houwelingen. Submitted for publication.

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