GENEHUNTER-IMPRINTING

GENEHUNTER-IMPRINTING performs parametric multi-marker and two-locus linkage analysis of dichotomous traits, modeling parent-of-origin imprinting by specifying two heterozygote penetrance parameters (four penetrances total) to differentiate paternal and maternal allele effects.

Key Features:

• Parametric multi-marker linkage analysis: Implements parametric LOD-score methods to analyze linkage of dichotomous traits while modeling imprinting via distinct heterozygote penetrance parameters.
• Two-locus linkage analysis: Supports multimarker analysis of linkage involving two trait loci to assess interactions and imprinting at each locus.
• Empirical significance testing: Performs simulation under the null hypothesis of no linkage to obtain empirical significance for MOD-score results across varying pedigree sizes and structures.
• Optimized computational efficiency: Employs parallelized computation to accelerate analysis of large pedigrees and complex genetic models.
• Interpretable 3-D visualization: Generates three-dimensional plots displaying LOD and NPL scores across genetic positions of both disease loci for visual interpretation.

Scientific Applications:

• Genetic mapping of multifactorial traits: Applied to map loci for complex traits such as sensitization to mite allergens and hypercholesterolemia where imprinting may contribute to inheritance.
• Investigation of parent-of-origin effects: Used to detect and model paternal versus maternal allele effects in diseases exhibiting imprinting.

Methodology:

Specifies two heterozygote penetrance parameters (four penetrances total) to model imprinting; conducts parametric LOD-score and nonparametric linkage (NPL) analyses including two-locus multimarker linkage; uses simulation under the null for empirical MOD-score significance and parallelized computation for performance; produces 3-D plots of LOD and NPL across locus positions.