title: Whole-genome molecular haplotyping of single cells.
abstract: Conventional experimental methods of studying the human genome are limited by the inability to independently study the combination of alleles, or haplotype, on each of the homologous copies of the chromosomes. We developed a microfluidic device capable of separating and amplifying homologous copies of each chromosome from a single human metaphase cell. Single-nucleotide polymorphism (SNP) array analysis of amplified DNA enabled us to achieve completely deterministic, whole-genome, personal haplotypes of four individuals, including a HapMap trio with European ancestry (CEU) and an unrelated European individual. The phases of alleles were determined at ∼99.8% accuracy for up to ∼96% of all assayed SNPs. We demonstrate several practical applications, including direct observation of recombination events in a family trio, deterministic phasing of deletions in individuals and direct measurement of the human leukocyte antigen haplotypes of an individual. Our approach has potential applications in personal genomics, single-cell genomics and statistical genetics.
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, California, USA.
authors.forename: H Christina
authors.initials: HC
authors.lastname: Fan
authors.forename: Jianbin
authors.initials: J
authors.lastname: Wang
authors.forename: Anastasia
authors.initials: A
authors.lastname: Potanina
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Quake
mesh_terms: D000483:Alleles; D002461:Cell Line, Transformed; D005060:Europe; D005190:Family; D005260:Female; D015894:Genome, Human / Q000235:genetics*; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology*; D008297:Male; D008677:Metaphase; D044085:Microfluidics / Q000295:instrumentation* / Q000379:methods; D010375:Pedigree; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011995:Recombination, Genetic; D044465:White People / Q000235:genetics
chemical_list: D006680:HLA Antigens