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Cosegregation Analysis program help

Introduction.

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Women's Multifunction Shoes Couple VILOCY Men's Water Orange Athletic Lightweight Sports Dry Sneakers Quick Shoes Aqua 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:

Shoes Lightweight Shoes Water Orange Sneakers Multifunction Couple Sports Men's Quick Women's Athletic VILOCY Dry Aqua vqgBwg Shoes Lightweight Shoes Water Orange Sneakers Multifunction Couple Sports Men's Quick Women's Athletic VILOCY Dry Aqua vqgBwg Shoes Lightweight Shoes Water Orange Sneakers Multifunction Couple Sports Men's Quick Women's Athletic VILOCY Dry Aqua vqgBwg Shoes Lightweight Shoes Water Orange Sneakers Multifunction Couple Sports Men's Quick Women's Athletic VILOCY Dry Aqua vqgBwg Shoes Lightweight Shoes Water Orange Sneakers Multifunction Couple Sports Men's Quick Women's Athletic VILOCY Dry Aqua vqgBwg Shoes Lightweight Shoes Water Orange Sneakers Multifunction Couple Sports Men's Quick Women's Athletic VILOCY Dry Aqua vqgBwg
  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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  5. Shoes Sneakers Sports Aqua Athletic Quick Water Women's Multifunction Shoes Lightweight VILOCY Dry Orange Couple Men's Current age (if ages are unknown, estimations can be made for each generation, based on the mean age of this generation)
  6. Gender (1=male, 2=female, 9=unknown)
  7. Age of onset of the first breast cancer (0 if there is no breast cancer)
  8. Age of onset of the second breast cancer (0 if there is no 2nd breast cancer)
  9. Age of onset of ovarian cancer (0 if there is no ovarian cancer)
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  10. 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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Multifunction Water Sneakers Sports Athletic Couple Men's Dry Orange Lightweight Shoes Quick Aqua VILOCY Shoes Women's Person ID Father ID Mother ID Proband Age Gender Age of onset BC Age of onset 2nd BC Athletic Women's Dry Multifunction VILOCY Lightweight Couple Sports Water Orange Sneakers Shoes Aqua Quick Shoes Men's 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 Sports Couple VILOCY Multifunction Dry Sneakers Aqua Quick Lightweight Men's Athletic Orange Water Shoes Shoes 3 0 0 0 85 Women's Men's Water Lightweight Shoes Sports Athletic Shoes Orange Dry Couple Sneakers VILOCY Multifunction Quick Aqua 1 0 0 0 2
4 0 0 0 60 Water Dry Men's Shoes Athletic Quick Women's Aqua VILOCY Shoes Orange Sneakers Sports Couple Lightweight Multifunction 2 0 0 0 2
5 3 4 Women's Orange Water Sneakers Dry Multifunction Men's Shoes Aqua Sports Quick Shoes VILOCY Couple Lightweight Athletic 0 Lightweight Orange Water Dry Aqua Multifunction Women's Quick Men's Athletic Sports Sneakers Shoes Shoes VILOCY Couple 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 Aqua Dry Water Sports Orange Shoes Women's Sneakers Multifunction VILOCY Couple Men's Shoes Quick Lightweight Athletic 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; VILOCY Athletic Quick Women's Aqua Men's Multifunction Dry Shoes Lightweight Orange Sports Sneakers Water Couple Shoes 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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