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Part 2: Linkage Analysis

 

 

Results from test:

Family: 4329

 

            Theta  Theta  Theta  Theta  Theta  Theta   Theta  Max

   Locus    0.001  0.01   0.05   0.10   0.20   0.30    Max    LOD

------------------------------------------------------------------

  D6S263   -0.84  -0.74  -0.45  -0.22   0.01   0.10    0.34   0.10

  D6S259   -1.05  -0.64  -0.11   0.11   0.23   0.20    0.22   0.23

  D6S285   -1.07  -0.64  -0.11   0.11   0.23   0.20    0.22   0.23

  D6S105   -0.40  -0.37  -0.26  -0.15  -0.03   0.01    0.33   0.01

 D6S1051   -0.40  -0.37  -0.26  -0.15  -0.03   0.01    0.33   0.01

 D6S1017   -0.53  -0.49  -0.34  -0.20  -0.06  -0.00    0.37   0.00

  D6S271    0.61   0.61   0.60   0.56   0.43   0.25    0.01   0.61

 D6S1280   -1.12  -1.06  -0.87  -0.70  -0.46  -0.28    0.50   0.00

  D6S254   -0.00  -0.00  -0.00  -0.00  -0.00  -0.00    0.50   0.00

  D6S251   -0.40  -0.37  -0.29  -0.21  -0.11  -0.04    0.50   0.00

  D6S300   -0.17  -0.15  -0.07  -0.00   0.05   0.04    0.23   0.05

 D6S1021   -0.38  -0.36  -0.28  -0.20  -0.10  -0.04    0.50   0.00

  D6S474   -0.56  -0.53  -0.40  -0.27  -0.12  -0.07    0.50   0.00

 D6S1040   -1.32  -1.24  -0.96  -0.73  -0.43  -0.25    0.50   0.00

 D6S1003   -0.71  -0.67  -0.55  -0.41  -0.22  -0.09    0.50   0.00

 D6S1007    1.61   1.58   1.46   1.30   0.97   0.60    0.00   1.61

  D6S305    1.86   1.83   1.69   1.51   1.13   0.71    0.00   1.86

  D6S264    1.40   1.37   1.26   1.13   0.83   0.51    0.00   1.40

  D6S503   -1.27  -1.21  -0.96  -0.71  -0.36  -0.15    0.50   0.00

 D6S1027   -1.09  -1.04  -0.83  -0.62  -0.32  -0.14    0.50   0.00

 

So what does this table of results mean?

Using the information that you supplied from the pedigree as well as individual genotypes, marker information, and information about Alzheimer Disease, parametric linkage analysis results have been calculated for chromosome 6.  The program used was a PERL script (freely available at http://ggcepi.tripod.com/linkage.html) that easily runs the FASTLINK program (Cottingham, Schaffer) and linkage auxiliary programs.

The table shows the chromosome 6 markers analyzed listed from pter to qter.  LOD scores were calculated for given thetas (recombination fractions--a measure of distance from the disease locus).  The LOD score tells us how likely it is that a particular genetic marker is inherited with the disease.  The value is based on a logarithmic scale, therefore, a LOD score of 1 means that the marker is 10 times more likely to be linked to the disease than an unlinked marker.  A LOD score of 2 means that it is 100 times more likely to be linked.

Notice in the table above that there is a region of loci with LOD scores over "1": D6S1007, D6S305, and D6S264.  These LOD scores mean that it is likely that this region is inherited along with Alzheimer Disease.  However, there are many genes contained in this region.  How do you go about choosing which gene to sequence for disease-causing mutations in this family?

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