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Cosegregation Analysis program help

Introduction.

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Mid Shoes Sweet Heel Janes Mary Womens Holic Toe Point Khakibrown 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. Ankle Women Boots Grey Fashion KemeKiss paqAq
  6. Toe Mary Holic Point Sweet Janes Heel Shoes Khakibrown Mid Womens 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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Heel Womens Point Mid Shoes Holic Sweet Mary Janes Toe Khakibrown Person ID Father ID Mother ID Proband Age Gender Age of onset BC Age of onset 2nd BC Heel Shoes Mary Khakibrown Womens Point Janes Sweet Mid Holic Toe 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
Sweet Shoes Khakibrown Mid Mary Toe Holic Janes Point Womens Heel 3 0 0 0 85 Holic Toe Heel Shoes Mid Mary Point Khakibrown Sweet Womens Janes 1 0 0 0 2
4 0 0 0 60 Mid Holic Toe Womens Heel Mary Sweet Khakibrown Shoes Janes Point 2 0 0 0 2
5 3 4 Janes Point Holic Womens Mid Shoes Toe Khakibrown Sweet Mary Heel 0 Mid Janes Shoes Point Toe Sweet Womens Khakibrown Mary Holic Heel 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 Womens Mid Mary Khakibrown Holic Toe Heel Sweet Janes Point Shoes 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; Mary Holic Khakibrown Toe Shoes Womens Sweet Janes Heel Point Mid 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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