Chromosomal Haplotypes by Genetic Phasing of Human Families

Assignment of alleles to haplotypes for nearly all the variants on all chromosomes can be performed by genetic analysis of a nuclear family with three or more children. Whole-genome sequence data enable deterministic phasing of nearly all sequenced alleles by permitting assignment of recombinations...

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Bibliographic Details
Published in:American journal of human genetics 2011-09, Vol.89 (3), p.382-397
Main Authors: Roach, Jared C., Glusman, Gustavo, Hubley, Robert, Montsaroff, Stephen Z., Holloway, Alisha K., Mauldin, Denise E., Srivastava, Deepak, Garg, Vidu, Pollard, Katherine S., Galas, David J., Hood, Leroy, Smit, Arian F.A.
Format: Article
Language:English
Subjects:
Algorithms
Biological and medical sciences
Chromosomes
Chromosomes, Human - genetics
Families & family life
Fundamental and applied biological sciences. Psychology
General aspects. Genetic counseling
Genetic algorithms
Genetic Variation
Genetics of eukaryotes. Biological and molecular evolution
Genotype & phenotype
Haplotypes
Haplotypes - genetics
Humans
Inheritance Patterns - genetics
Medical genetics
Medical sciences
Models, Genetic
Molecular and cellular biology
Mutation - genetics
Pedigree
Sequence Analysis, DNA - methods
Software
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Summary:Assignment of alleles to haplotypes for nearly all the variants on all chromosomes can be performed by genetic analysis of a nuclear family with three or more children. Whole-genome sequence data enable deterministic phasing of nearly all sequenced alleles by permitting assignment of recombinations to precise chromosomal positions and specific meioses. We demonstrate this process of genetic phasing on two families each with four children. We generate haplotypes for all of the children and their parents; these haplotypes span all genotyped positions, including rare variants. Misassignments of phase between variants (switch errors) are nearly absent. Our algorithm can also produce multimegabase haplotypes for nuclear families with just two children and can handle families with missing individuals. We implement our algorithm in a suite of software scripts (Haploscribe). Haplotypes and family genome sequences will become increasingly important for personalized medicine and for fundamental biology.
ISSN:0002-9297
1537-6605
DOI:10.1016/j.ajhg.2011.07.023