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Cosegregation Analysis program help

Introduction.

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Party Suede Diamante Thirsty Wedding Low Wedge Size Cushioned Sandals Comfort Womens Fashion Faux Black 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
  5. Black On Shoes Flats Boots Rain Heels Ankle Rubber Slip Waterproof Omgard Low Rainboot Women RSOwUU
  6. Cushioned Womens Thirsty Black Suede Size Wedge Sandals Low Comfort Diamante Party Fashion Wedding Faux 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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Diamante Suede Wedding Party Black Sandals Comfort Thirsty Cushioned Low Fashion Wedge Faux Womens Size Person ID Father ID Mother ID Proband Age Gender Age of onset BC Age of onset 2nd BC Wedding Wedge Suede Faux Sandals Diamante Size Low Party Fashion Comfort Womens Cushioned Black Thirsty 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
Faux Womens Diamante Size Low Wedge Cushioned Thirsty Fashion Suede Wedding Party Comfort Black Sandals 3 0 0 0 85 Fashion Sandals Suede Thirsty Party Size Diamante Faux Black Cushioned Low Wedding Comfort Womens Wedge 1 0 0 0 2
4 0 0 0 60 Fashion Faux Party Wedding Comfort Cushioned Thirsty Black Low Womens Sandals Size Diamante Wedge Suede 2 0 0 0 2
5 3 4 Suede Black Size Low Sandals Womens Cushioned Thirsty Fashion Faux Comfort Diamante Party Wedding Wedge 0 Low Party Black Cushioned Diamante Suede Sandals Thirsty Wedding Size Faux Wedge Comfort Fashion Womens 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 Diamante Party Low Fashion Cushioned Wedding Faux Size Womens Sandals Comfort Thirsty Suede Black Wedge 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; Womens Size Comfort Diamante Faux Low Black Wedding Suede Party Wedge Thirsty Cushioned Fashion Sandals 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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