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The Generalized Relative Pairs IBD Distribution: Its Use in the Detection of Linkage

View Article: PubMed Central - PubMed

ABSTRACT

I introduce a novel approach to derive the distribution of disease affectional status given alleles identical by descent (IBD) sharing through ITO method. My approach tremendously simplifies the calculation of the affectional status distribution compared to the conventional method, which requires the parental mating information, and could be applied to disease with both dichotomous trait and quantitative trait locus (QTL). This distribution is shown to be independent of relative relationship and be employed to develop the marker IBD distributions for relative relationship. In addition, three linkage tests: the proportion, the mean test, and the LOD score test are proposed for different relative pairs based on their marker IBD distributions. Among all three tests, the mean test for sib pair requires the least sample size, thus, has the highest power. Finally, I evaluate the significance of different relative relationships by a Monte-Carlo simulation approach.

No MeSH data available.


The comparison between the simulated and theoretical test powers of Sib Pairs. The simulated/calculated powers for proportion test (solid line/circle), the mean test (dotted line/triangle), and the LOD score test (medium dash/square) are plotted as a function of recombination fraction θ for sib pairs.
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Figure 4: The comparison between the simulated and theoretical test powers of Sib Pairs. The simulated/calculated powers for proportion test (solid line/circle), the mean test (dotted line/triangle), and the LOD score test (medium dash/square) are plotted as a function of recombination fraction θ for sib pairs.

Mentions: In this section, I perform the Monte-Carlo simulation procedures to evaluate the power of three statistical tests. The pedigree data consists of 300 replicates of 5 nuclear families. Within each nuclear family, there are two affected individuals with the dichotomous trait representing relative relationship of sibs, grandparent–grandchild, uncle–nephew, half sibs, and first cousin. Since the simulation programs use the parameters set {p, f1, f2, f3}, I take only one reasonable solution set for {KP, VA, VD} = {0.1, 0.01, 0.01}, where p = 0.7887 is the gene frequency of the normal allele, f1 = 0.05359, f2 = 0.1 are the first two penetrance frequencies of homozygous individual of normal alleles, and heterozygous individual, f3 = 0.7464 is the penetrance frequency of homozygous individual carrying recessive disease alleles. Total 100,000 data set were generated under different hypothesis of θ. The test power was then evaluated at putative α level of 0.05 for the proportion and mean test statistics, and α level of 0.001 for the LOD score test statistic. The simulated empirical powers are consistent with the theoretical calculations for all relative relationships, which serve as a validation of the test statistics, and result of sib pair is shown in Figure 4.


The Generalized Relative Pairs IBD Distribution: Its Use in the Detection of Linkage
The comparison between the simulated and theoretical test powers of Sib Pairs. The simulated/calculated powers for proportion test (solid line/circle), the mean test (dotted line/triangle), and the LOD score test (medium dash/square) are plotted as a function of recombination fraction θ for sib pairs.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5120125&req=5

Figure 4: The comparison between the simulated and theoretical test powers of Sib Pairs. The simulated/calculated powers for proportion test (solid line/circle), the mean test (dotted line/triangle), and the LOD score test (medium dash/square) are plotted as a function of recombination fraction θ for sib pairs.
Mentions: In this section, I perform the Monte-Carlo simulation procedures to evaluate the power of three statistical tests. The pedigree data consists of 300 replicates of 5 nuclear families. Within each nuclear family, there are two affected individuals with the dichotomous trait representing relative relationship of sibs, grandparent–grandchild, uncle–nephew, half sibs, and first cousin. Since the simulation programs use the parameters set {p, f1, f2, f3}, I take only one reasonable solution set for {KP, VA, VD} = {0.1, 0.01, 0.01}, where p = 0.7887 is the gene frequency of the normal allele, f1 = 0.05359, f2 = 0.1 are the first two penetrance frequencies of homozygous individual of normal alleles, and heterozygous individual, f3 = 0.7464 is the penetrance frequency of homozygous individual carrying recessive disease alleles. Total 100,000 data set were generated under different hypothesis of θ. The test power was then evaluated at putative α level of 0.05 for the proportion and mean test statistics, and α level of 0.001 for the LOD score test statistic. The simulated empirical powers are consistent with the theoretical calculations for all relative relationships, which serve as a validation of the test statistics, and result of sib pair is shown in Figure 4.

View Article: PubMed Central - PubMed

ABSTRACT

I introduce a novel approach to derive the distribution of disease affectional status given alleles identical by descent (IBD) sharing through ITO method. My approach tremendously simplifies the calculation of the affectional status distribution compared to the conventional method, which requires the parental mating information, and could be applied to disease with both dichotomous trait and quantitative trait locus (QTL). This distribution is shown to be independent of relative relationship and be employed to develop the marker IBD distributions for relative relationship. In addition, three linkage tests: the proportion, the mean test, and the LOD score test are proposed for different relative pairs based on their marker IBD distributions. Among all three tests, the mean test for sib pair requires the least sample size, thus, has the highest power. Finally, I evaluate the significance of different relative relationships by a Monte-Carlo simulation approach.

No MeSH data available.