Lectures 29-30 Statistical evaluation of Genetic Linkage . Phase Lod scores
Lectures 29-30: •Phase •Lod scores Statistical Evaluation of Genetic Linkage
genetIc linkage mapping We genotype the six members of the family for SSrs scattered throughout the genome(which spans 3300 CM) one SSR must be within 10 cM of the Huntington's gene HD SSR12 SSR112 SSR31 SSR37 SSR5 20 CM
20 cM SSR12 SSR112 SSR31 SSR37 SSR5 genetic linkage mapping We genotype the six members of the family for SSRs scattered throughout the genome (which spans 3300 cM)— one SSR must be within 10 cM of the Huntington's gene: HD ?
LODoos(family1)=log0(0.024/0039)=0g10(6.25)=0796 Same for families #2 and#3 2LoDo6( families1,2,3)=3x0.796=2388 Family #4 Maternal HD HDHD HD alleles SSR37 D D D D P if linked at 0.06=1/2(P if phase 1)+1/2(P if phase 2) =12(0.47X0.47X0.03X0.47)+1/2(0.03×0.03X0.47X003)=0.0016 ODo6eamy4)=log10(0.00160.0039)=0g10(0.41)=-0387
log10 (0.024/0.0039) Same for families #2 and #3: LOD0.06 (families 1, 2, 3) = 3 x 0.796 = 2.388 Family #4: SSR37 D D D D Maternal HD HD HD + HD alleles P if linked at 0.06 = 1/2 (P if phase 1) + 1/2 (P if phase 2) = 1/2 LOD0.06 (family 4) LOD0.06(family 1) = = log10 (6.25) = 0.796 (0.47 x 0.47 x 0.03 x 0.47) + 1/2 (0.03 x 0.03 x 0.47 x 0.03) = 0.0016 = log10 = log (0.41) 10 (0.0016/0.0039) = - 0.387
2LoD6ames1,2,3,4)=2388-0.387=2001 Still not sufficient to publish. What to do? 1. It's tempting to ignore family 4- to declare it to be irrelevant for some reason or another But this would not be an acceptable solution 2. Calculate LOD scores for other 0 values? 1.5 LOD 0.2 0.3 0.5 -0.5 6
LOD0.06 (families 1, 2, 3, 4) = 2.388 – 0.387 = 2.001 Still not sufficient to publish. What to do? 1. It's tempting to ignore family 4 — But this would not be an acceptable solution. 2. Calculate LOD scores for other values? to declare it to be irrelevant for some reason or another. -0.5 0 0.5 1 1.5 2 2.5 0 0.1 0.2 0.3 0.4 0.5 0.6 LOD
3. Get more families always a good idea 4. Determine phase in affected parents In each of the four families, we were uncertain about phase, and our LOd calculations embodied those uncertainties Family #4 HD SSR37 Phase HD 1: B two possible arrangements of alleles on mother's chromosomes Phase HD BD
3. 4. Get more families — always a good idea Determine phase in affected parents In each of the four families, we were uncertain about phase, and our LOD calculations embodied those uncertainties. Family #4: + D Phase HD B 2: + B Phase HD D 1: HD SSR37 two possible arrangements of alleles on mother's chromosomes