What methods are used for haplotype phasing and why is it important?

Haplotype phasing determines which alleles are on the same chromosome, critical for: compound heterozygosity assessment, population genetics, disease inheritance patterns, and personalized medicine. Methods: 1) Statistical phasing - uses population reference panels (1000 Genomes, TOPMed) and linkage disequilibrium patterns; tools: SHAPEIT, Eagle, Beagle; accurate for common variants. 2) Read-backed phasing - phase nearby variants covered by same read/read-pair; limited by read/fragment length; WhatsHap, HapCUT2. 3) Long-read phasing - PacBio HiFi and ONR reads span many variants; enables direct phasing over tens of kb. 4) Linked-read phasing (10x Genomics) - molecular barcodes link reads from same molecule. 5) Family-based phasing - use parental genotypes for complete phasing. 6) Hi-C phasing - chromatin contacts provide chromosome-scale phasing. Challenges: rare variants, complex regions, computational cost for long-range phasing.