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Cosegregation Analysis program help

Introduction.

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