HS-TDT

HS-TDT performs haplotype-sharing transmission/disequilibrium testing to detect association and linkage between multimarker haplotypes and disease-susceptibility loci in nuclear pedigrees.

Key Features:

• Haplotype-Based Analysis: Considers multiple tightly linked markers as multimarker haplotypes rather than treating markers independently, increasing informativeness for detecting disease-associated loci.
• Efficient Degrees of Freedom Management: Controls degrees of freedom so they increase linearly with the number of markers and do not depend on the number of alleles per marker, reducing dimensionality compared to conventional methods.
• Applicability Across Traits and Family Structures: Applies to quantitative and qualitative traits in nuclear families of any size and accommodates ambiguous or missing parental haplotype phase information.
• Robustness and Power: Maintains correct type I error in structured populations and often exhibits higher statistical power than single-marker TDTs and other haplotype-based TDTs according to simulation studies.

Scientific Applications:

• Linkage and Association Mapping: Localizes disease-susceptibility loci in chromosomal regions characterized by tightly linked markers using haplotype transmission signals.
• Family-Based Genetic Studies: Analyzes genetic associations in nuclear pedigrees of varying sizes and in datasets with missing or ambiguous parental phase.
• Rare and Complex Traits: Supports investigations of rare diseases and traits with complex inheritance patterns where multimarker haplotypes can improve detection power.

Methodology:

Analyzes haplotype sharing by testing transmission of multimarker haplotype blocks from parents to affected offspring rather than individual markers.