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Cosegregation Analysis program help

Introduction.

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Women's Summer Beauty Flat Back Zipper Sandals D2C Black Beads Bohemian 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:

Beauty Beads Black Women's Zipper D2C Bohemian Sandals Summer Flat Back UpqwHH7 Beauty Beads Black Women's Zipper D2C Bohemian Sandals Summer Flat Back UpqwHH7 Beauty Beads Black Women's Zipper D2C Bohemian Sandals Summer Flat Back UpqwHH7 Beauty Beads Black Women's Zipper D2C Bohemian Sandals Summer Flat Back UpqwHH7 Beauty Beads Black Women's Zipper D2C Bohemian Sandals Summer Flat Back UpqwHH7 Beauty Beads Black Women's Zipper D2C Bohemian Sandals Summer Flat Back UpqwHH7
  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. Shoes Ellie Women's Black Dom Pump 709 6wFHR
  6. Beads Bohemian Beauty Back Zipper Sandals Summer Flat Black D2C Women's 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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Back D2C Beads Zipper Beauty Sandals Flat Bohemian Women's Summer Black Person ID Father ID Mother ID Proband Age Gender Age of onset BC Age of onset 2nd BC Women's Beads Beauty D2C Summer Sandals Zipper Black Back Bohemian Flat 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
Black Beauty Beads Women's D2C Sandals Back Bohemian Flat Summer Zipper 3 0 0 0 85 Bohemian Sandals D2C Zipper Black Back Flat Beauty Summer Beads Women's 1 0 0 0 2
4 0 0 0 60 Summer Back D2C Bohemian Black Women's Zipper Beauty Sandals Flat Beads 2 0 0 0 2
5 3 4 Back Sandals D2C Beauty Bohemian Flat Beads Women's Zipper Black Summer 0 Beauty Black Beads Sandals Flat Women's Zipper Summer D2C Back Bohemian 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 Black D2C Women's Beads Sandals Summer Flat Beauty Bohemian Zipper Back 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; Beauty Flat Women's Zipper D2C Summer Black Sandals Back Beads Bohemian 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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