nucular

nucular transforms extended pedigrees into nuclear families to enable genetic linkage and imprinting analyses that test parent-of-origin effects in samples of affected siblings.

Key Features:

• Artificial recoding: Recodes full siblings as half-siblings by assigning distinct mothers or fathers to represent parental origin-specific transmission.
• Multipoint procedure: Employs a multipoint linkage procedure enabling tests of maternal versus paternal linkage and detection of imprinting in linked regions.
• Compatibility with standard statistical analyses: Produces transformed datasets suitable for downstream application of standard analytical methods.
• Type I error control: Simulations indicate no inflation of type I error rates in unlinked regions even with large differences between sex-specific genetic maps.
• Bias consideration in linked regions: Notes potential bias in imprinting tests under the null hypothesis in linked regions due to discrepancies in sex-specific maps regardless of the map used for analysis.

Scientific Applications:

• Parent-of-origin analyses in linkage studies: Tests for parental-origin effects and imprinting in samples of affected siblings within genetic linkage analyses.
• Application to the Collaborative Study on the Genetics of Alcoholism (CSGA) dataset (Genetic Analysis Workshop 14): Detected significant paternal linkage to 6q25 in affected brothers (p = 0.00038) and modest evidence for imprinting (p = 0.018) in a region containing the OPRM1 gene.

Methodology:

Transforms extended pedigrees into nuclear families by recoding siblings; applies a multipoint procedure to test linkage and imprinting; uses standard statistical analyses on transformed data; and conducts simulations to assess type I error behavior.