Haplotyping

Haplotyping is the process of determining haplotypes, the specific combination of alleles at neighboring loci that are inherited together on the same chromosome. A haplotype represents the chromosomal segment carried on a single parental chromosome, in contrast to a genotype, which records only the pair of alleles at each locus without specifying their chromosomal phase. Understanding haplotypes helps reveal patterns of linkage disequilibrium, recombination, and the genetic architecture of traits and diseases.

Haplotyping can be performed by experimental and computational methods. Family-based phasing uses inheritance in pedigrees to assign alleles to parental chromosomes. Statistical phasing employs genotype data from many individuals and reference panels to infer likely haplotype configurations. Recent advances combine large reference panels with sophisticated algorithms (for example, methods used in contemporary phasing software). Direct haplotyping is possible with long-read sequencing technologies that read long DNA molecules, linked-read approaches, or chromosome conformation capture methods (such as Hi-C), which can assign alleles to the same chromosome over long distances. In polyploid organisms or mosaic samples, haplotyping becomes more complex.

Applications include haplotype-based genome-wide association studies, improved genotype imputation, construction of haplotype-resolved genome sequences, and pharmacogenomics, where drug response may track specific haplotypes. Population genetics studies use haplotypes to trace ancestry and recombination history. Challenges include phasing accuracy in regions of low linkage disequilibrium, the presence of recombination breakpoints, errors from sequencing, and higher complexity in polyploid or tumor samples.

Overall, haplotyping provides a more complete view of genetic variation than single-locus genotypes and is central to many modern genomic analyses.