Figure 1.
Genetic relatedness plots of the Human Variation Panel genotype data.
Abbreviations: AA, African American; CAU, Caucasian; CHI, Chinese; MEX, Mexican. (A) IBS2* plot of the within-group comparisons (n = 19,800). The IBS2*_ratio values are centered on 2/3 for unrelated individuals within a population. The relationship of NA17251 to 99 other AA individuals is indicated (arrow). A group of 9 MEX individuals have atypically low heterozygosity rates and form a cluster separated from other within-MEX comparisons (arrow 1). (B) IBS2* plot in which pairwise comparisons with IBS2*_ratio values >0.8 are removed (n = 13) and data points are colored by the sum of autosomal heterozygosity of each pair of individuals. (C) IBS2* plot for between-group comparisons (n = 60,000) for which none are expected to be genetically related. For groups having individuals with large differences in heterozygosity rates, such as AA-CHI comparisons, the IBS2*_ratio values are significantly lower than 2/3. The MEX individuals with atypical heterozygosity rates tend to form outlier clusters in between-group comparisons such as AA-MEX (arrow 1) and CHI-MEX (arrow 2). A group of five pairwise comparisons having relatively high IBS2*_ratio values (0.685 to 0.692; arrow 3) involve MEX individual NA17709 in comparison to CAU individuals.
Figure 2.
Visualization of shared chromosomal regions based on IBS for related individuals.
IBS values for comparisons of two individuals are shown for a representative chromosome for the following pairs: (A) replicate samples NA17255/NA17263, (B) parent-child NA17624/NA17626, (C) full siblings NA17671/NA17674, (D) individuals sharing one quarter of their alleles (NA17655/NA17656; e.g. half-siblings), (E) distantly related individuals NA17673/NA17680. Data analysis was performed using SNPduo software. Note that for pericentromeric regions and the short arms of acrocentric chromosomes (as in panel C) no SNP data were available, producing no IBS measurements.
Table 1.
Unexpected relationships inferred in the Coriell Human Variation Panel.
Figure 3.
Relationship of IBS2* values to IBD estimates for recently related within-group comparisons.
IBS2* plots for recently related within-group comparisons having IBS2*_ratio values >0.80. The y-axis shows IBD1 and IBD2 estimates derived from our approach (K1, panel A; K2, panel B), PLINK's HMM which had removed individuals due to low genotyping rates (Z1, panel C; Z2, panel D), and PLINK's HMM with the same quality control metrics except that no individuals were removed (Z1, panel E; Z2, panel F). Note that the x-axis and y-axis scales are the same for panels A–F. Arrows and brackets indicate groups of pairwise comparisons representing one relationship type (see text for details). Colors correspond to ethnic group and are matched across the four panels.
Figure 4.
Relationship of IBS2* values to IBD estimates for distantly related within-group comparisons.
IBS2* plots for within-group comparisons having IBS2*_ratio values <0.76 are shown. The y-axis shows IBD1 and IBD2 estimates derived from our approach (panels A, B) and PLINK's HMM which had removed individuals due to low genotype rates (panels C, D). Note that the x-axes scales are the same for all panels, and the y-axes are comparable for panels A, C and B, D. Arrows indicate pairwise comparisons: arrow 1, NA17673/NA17680 (MEX; see also arrow 1 in Figure 1A, 1B); arrow 2, NA17454/NA17459 (MEX; see also arrow 1 in Figure 1A, 1B); arrow 3, NA17203/NA17257 (CAU); arrow 4, NA17289/NA17299 (CAU); arrow 5, NA17785/NA17794 (CHI).
Figure 5.
Validation of IBS2* methodology using annotated relationships from a known pedigree.
IBS2* plot analysis of real data from a large pedigree annotated by distance (i.e. proportion of IBD). The y-axis shows IBD1 and IBD2 estimates derived from our approach (panels A, C) and PLINK's HMM (panels B, D). These distances refer to Cotterman coefficients of relatedness. Note the linear relationship between K1and Z1 and IBS2*_ratio values in panels A and C.
Table 2.
IBD estimates in annotated relationships.
Table 3.
IBS probabilities given IBD state.