Detecting autozygosity through runs of homozygosity: A comparison of three autozygosity detection algorithms
Year: 2011
Type: article
Abstract: BACKGROUND: A central aim for studying runs of homozygosity (ROHs) in genome-wide SNP data is to detect the effects of autozygosity (stretches of the two homologous chromosomes within the same individual that are identical by descent) on phenotypes. However, it is unknown which current ROH detection program, and which set of parameters within a given program, is optimal for differentiating ROHs that are truly autozygous from ROHs that are homozygous at the marker level but vary at unmeasured variants between the markers. METHOD: We simulated 120 Mb of sequence data in order to know the true state of autozygosity. We then extracted common variants from this sequence to mimic the properties of SNP platforms and performed ROH analyses using three popular ROH detection programs, PLINK, GERMLINE, and BEAGLE. We varied detection thresholds for each program (e.g., prior probabilities, lengths of ROHs) to understand their effects on detecting known autozygosity. RESULTS: Within the optimal thresholds for each program, PLINK outperformed GERMLINE and BEAGLE in detecting autozygosity from distant common ancestors. PLINK's sliding window algorithm worked best when using SNP data pruned for linkage disequilibrium (LD). CONCLUSION: Our results provide both general and specific recommendations for maximizing autozygosity detection in genome-wide SNP data, and should apply equally well to research on whole-genome autozygosity burden or to research on whether specific autozygous regions are predictive using association mapping methods.
Source: BMC Genomics
Institution: University of Colorado Boulder
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,090
Awards: DIAGNOSTIC CENTER FOR LINKAGE STUDIES OF SCHIZOPHRENIA, G3096205748, Molecular Genetics of Schizophrenia, LINKAGE STUDIES OF SCHIZOPHRENIA, Molecular Genetics of Schizophrenia, Molecular Genetics of Schizophrenia, Molecular Genetics of Schizophrenia, Genome-Wide Association Study of Schizophrenia, Molecular Genetics of Schizophrenia, DIAGNOSTIC CENTER FOR SCHIZOPHRENIA LINKAGE STUDIES, A Genome-Wide Association Study of Schizophrenia, Evolutionary Roles of Homozygosity & Copy Number Variation in Mental Disorders, Molecular Genetics of Schizophrenia, Molecular Genetics of Schizophrenia, Molecular Genetics of Schizophrenia, Research Training - Developmental Behavioral Genetics, Molecular Genetics of Schizophrenia, Genome-wide Association Study of Schizophrenia, Molecular Genetics of Schizophrenia, Research Training - Mental Health Behavior Genetics
OpenAlex ID: W2029395646