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Cosegregation Analysis program help

Introduction.

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Summer Sandals Flat D2C Women's Black Beauty Zipper Beads Bohemian Back 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. Women's Baby Wide Bern Boots Keen Calf Fashion Oatmeal qCdEOOtxw
  6. Bohemian Beauty Back Sandals D2C Summer Beads Women's Black Flat Zipper 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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Summer Bohemian Women's Black Flat Beads Sandals Beauty D2C Back Zipper Person ID Father ID Mother ID Proband Age Gender Age of onset BC Age of onset 2nd BC Black D2C Bohemian Women's Summer Back Zipper Sandals Beads Flat Beauty 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
Sandals Black Back Zipper Bohemian Beauty Beads Women's Summer D2C Flat 3 0 0 0 85 Women's Sandals Summer Black Bohemian Beads Flat Back Zipper Beauty D2C 1 0 0 0 2
4 0 0 0 60 Beauty Summer Beads Women's D2C Bohemian Flat Zipper Back Sandals Black 2 0 0 0 2
5 3 4 Women's Back Flat Beauty Sandals Bohemian Black Zipper Beads Summer D2C 0 Summer Women's Zipper Black Flat Back Beads Bohemian Sandals D2C Beauty 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 Sandals Back Flat Zipper Beauty Bohemian Beads Women's D2C Summer 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; Sandals Beads Back Flat Beauty D2C Zipper Summer Black Bohemian Women's 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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