Comparative assessment of methods for estimating individual genome-wide homozygosity-by-descent from human genomic data - PubMed (original) (raw)
Comparative Study
doi: 10.1186/1471-2164-11-139.
Caroline Hayward, Celine Bellenguez, Veronique Vitart, Ivana Kolcić, Ruth McQuillan, Vanja Saftić, Ulf Gyllensten, James F Wilson, Igor Rudan, Alan F Wright, Harry Campbell, Anne-Louise Leutenegger
Affiliations
- PMID: 20184767
- PMCID: PMC2848240
- DOI: 10.1186/1471-2164-11-139
Comparative Study
Comparative assessment of methods for estimating individual genome-wide homozygosity-by-descent from human genomic data
Ozren Polasek et al. BMC Genomics. 2010.
Abstract
Background: Genome-wide homozygosity estimation from genomic data is becoming an increasingly interesting research topic. The aim of this study was to compare different methods for estimating individual homozygosity-by-descent based on the information from human genome-wide scans rather than genealogies. We considered the four most commonly used methods and investigated their applicability to single-nucleotide polymorphism (SNP) data in both a simulation study and by using the human genotyped data. A total of 986 inhabitants from the isolated Island of Vis, Croatia (where inbreeding is present, but no pedigree-based inbreeding was observed at the level of F > 0.0625) were included in this study. All individuals were genotyped with the Illumina HumanHap300 array with 317,503 SNP markers.
Results: Simulation data suggested that multi-point FEstim is the method most strongly correlated to true homozygosity-by-descent. Correlation coefficients between the homozygosity-by-descent estimates were high but only for inbred individuals, with nearly absolute correlation between single-point measures.
Conclusions: Deciding who is really inbred is a methodological challenge where multi-point approaches can be very helpful once the set of SNP markers is filtered to remove linkage disequilibrium. The use of several different methodological approaches and hence different homozygosity measures can help to distinguish between homozygosity-by-state and homozygosity-by-descent in studies investigating the effects of genomic autozygosity on human health.
Figures
Figure 1
Geographical position and settlements on the Vis Island, Croatia.
Figure 2
Scatterplot of FEstim using two marker selections, M0.1 and M0.05. Dashed line is a reference line (y = x).
Figure 3
Grandparental birthplace clusters and their homozygosity estimates using MLH (full marker count). Numbers on the figure are P values of pair-wise comparisons between neighbouring group homozygosity estimates using Mann-Whitney test.
Figure 4
Grandparental birthplace clusters and their homozygosity estimates using FADC (full marker count). Numbers on the figure are P values of pair-wise comparisons between neighbouring group homozygosity estimates using Mann-Whitney test. Plot for FPLINK is not shown here due to very high correlation coefficient with FADC.
Figure 5
Grandparental birthplace clusters and their homozygosity estimates using FEstim (M0.05 selection). Numbers on the figure are P values of pair-wise comparisons between neighbouring group homozygosity estimates using Mann-Whitney test.
References
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- Kristensen TN, Sorensen AC. Inbreeding - lessons from animal breeding, evolutionary biology and conservation genetics. Animal Science. 2005;80:121–133.
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