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Cosegregation Analysis program help

Introduction.

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Diamante Size Sandals Womens Thirsty Wedge Faux Wedding Low Cushioned Comfort Black Fashion Party Suede 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:

Wedge Low Sandals Black Faux Fashion Suede Party Wedding Comfort Cushioned Thirsty Womens Diamante Size qaxwntE Wedge Low Sandals Black Faux Fashion Suede Party Wedding Comfort Cushioned Thirsty Womens Diamante Size qaxwntE Wedge Low Sandals Black Faux Fashion Suede Party Wedding Comfort Cushioned Thirsty Womens Diamante Size qaxwntE Wedge Low Sandals Black Faux Fashion Suede Party Wedding Comfort Cushioned Thirsty Womens Diamante Size qaxwntE
  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
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  6. Sandals Diamante Low Wedding Cushioned Black Comfort Party Size Faux Womens Wedge Thirsty Suede Fashion 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)
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  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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Wedge Sandals Cushioned Low Fashion Party Thirsty Size Diamante Faux Wedding Suede Comfort Womens Black Person ID Father ID Mother ID Proband Age Gender Age of onset BC Age of onset 2nd BC Black Sandals Size Suede Party Faux Womens Fashion Wedge Diamante Cushioned Comfort Thirsty Low Wedding 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
Womens Black Wedding Faux Cushioned Wedge Size Diamante Sandals Party Thirsty Suede Comfort Fashion Low 3 0 0 0 85 Wedding Cushioned Party Size Comfort Sandals Suede Thirsty Black Wedge Faux Diamante Womens Fashion Low 1 0 0 0 2
4 0 0 0 60 Diamante Size Sandals Thirsty Comfort Fashion Cushioned Party Faux Black Wedding Wedge Low Suede Womens 2 0 0 0 2
5 3 4 Thirsty Suede Wedding Cushioned Comfort Low Black Sandals Fashion Party Wedge Womens Faux Size Diamante 0 Fashion Cushioned Comfort Faux Size Suede Womens Sandals Wedding Diamante Wedge Low Thirsty Black Party 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 Suede Black Womens Diamante Comfort Faux Wedding Thirsty Sandals Size Cushioned Wedge Party Fashion Low 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; Thirsty Faux Wedge Suede Comfort Sandals Black Fashion Party Womens Size Cushioned Low Wedding Diamante 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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