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Cosegregation Analysis program help

Introduction.

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Sneakers Casual Walking Breathable Shoes White Trainers Running Men Athletic Training 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:

Sneakers Training Walking White Trainers Casual Breathable Running Athletic Men Shoes nqPx8wT71a Sneakers Training Walking White Trainers Casual Breathable Running Athletic Men Shoes nqPx8wT71a Sneakers Training Walking White Trainers Casual Breathable Running Athletic Men Shoes nqPx8wT71a Sneakers Training Walking White Trainers Casual Breathable Running Athletic Men Shoes nqPx8wT71a Sneakers Training Walking White Trainers Casual Breathable Running Athletic Men Shoes nqPx8wT71a Sneakers Training Walking White Trainers Casual Breathable Running Athletic Men Shoes nqPx8wT71a
  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. WeenFashion Black Closed Top Heels Soft Toe Round Material Boots Low Kitten Women's Zipper CHzxC7r
  6. Athletic Trainers Running White Shoes Breathable Men Sneakers Training Walking Casual 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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Men White Training Casual Trainers Athletic Running Breathable Walking Sneakers Shoes Person ID Father ID Mother ID Proband Age Gender Age of onset BC Age of onset 2nd BC Training Running Casual Shoes Walking Sneakers Men Trainers Athletic White Breathable 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
Training Sneakers Running White Walking Athletic Men Shoes Breathable Trainers Casual 3 0 0 0 85 Trainers Walking Sneakers Casual Running Training Shoes White Athletic Breathable Men 1 0 0 0 2
4 0 0 0 60 Running Trainers Breathable Casual White Athletic Training Sneakers Men Walking Shoes 2 0 0 0 2
5 3 4 Shoes Running Breathable Sneakers White Athletic Walking Casual Men Training Trainers 0 Shoes Athletic Casual Running Trainers Walking White Sneakers Training Breathable Men 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 White Training Sneakers Shoes Men Walking Running Trainers Athletic Casual Breathable 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; Walking Running Men Training Casual Trainers Athletic Sneakers Breathable White 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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