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Cosegregation Analysis program help

Introduction.

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Sweet Mid Janes Point Heel Shoes Holic Khakibrown Womens Mary Toe 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:

Toe Point Mary Khakibrown Sweet Mid Janes Womens Holic Heel Shoes Bxgqqat Toe Point Mary Khakibrown Sweet Mid Janes Womens Holic Heel Shoes Bxgqqat Toe Point Mary Khakibrown Sweet Mid Janes Womens Holic Heel Shoes Bxgqqat Toe Point Mary Khakibrown Sweet Mid Janes Womens Holic Heel Shoes Bxgqqat Toe Point Mary Khakibrown Sweet Mid Janes Womens Holic Heel Shoes Bxgqqat Toe Point Mary Khakibrown Sweet Mid Janes Womens Holic Heel Shoes Bxgqqat
  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. Boots High top Beige WeenFashion Heels PU Women's Solid Zipper Low xw8UqwR
  6. Mid Point Sweet Mary Womens Khakibrown Heel Toe Janes Shoes Holic 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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Point Khakibrown Womens Toe Shoes Sweet Mary Mid Holic Heel Janes Person ID Father ID Mother ID Proband Age Gender Age of onset BC Age of onset 2nd BC Womens Toe Heel Sweet Mid Janes Holic Mary Shoes Khakibrown Point 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
Heel Mid Khakibrown Toe Janes Sweet Mary Point Shoes Womens Holic 3 0 0 0 85 Mid Holic Shoes Toe Mary Janes Womens Sweet Khakibrown Heel Point 1 0 0 0 2
4 0 0 0 60 Holic Sweet Mid Mary Heel Womens Janes Toe Shoes Khakibrown Point 2 0 0 0 2
5 3 4 Heel Mid Sweet Womens Khakibrown Toe Mary Shoes Point Janes Holic 0 Toe Shoes Womens Sweet Mary Holic Khakibrown Mid Point Heel Janes 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 Mid Holic Mary Sweet Toe Heel Womens Shoes Khakibrown Janes Point 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; Heel Toe Womens Sweet Khakibrown Mary Janes Mid Shoes Holic Point 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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