Two new approaches for experimentally determining a person’s haplotype — the combination of gene variants on each of the two copies of the chromosomes — are published in this week’s Nature Biotechnology. These strategies will be useful to uncover the genetic basis of disease with potential use in medical diagnosis.
Humans have two copies of each gene, one from each parent; variants on these genes are called alleles. The combination of these alleles makes each of us unique.
Until now, haplotyping an entire human genome required expensive, often impractical, experiments or statistical methods that generated imperfect estimations. Stephen Quake and colleagues have created a device that separates the chromosomes from a single cell into individual chambers for further analysis. They use the approach to analyze patterns of inheritance of genetic mutations in a family and to perform a clinically relevant test of genes related to the immune system that influence susceptibility to autoimmune and infectious diseases.
Taking an alternative approach, Jay Shendure and colleagues use a new protocol for preparing DNA for whole-genome sequencing that enables them to simultaneously determine haplotypes. They apply the method in sequencing the first genome of an individual with ancestry from the Indian subcontinent.