A strategy to improve phasing of whole-genome sequenced individuals through integration of familial information from dense genotype panels

Genetics, Selection, Evolution : GSE
Pierre Faux, Tom Druet

Abstract

Haplotype reconstruction (phasing) is an essential step in many applications, including imputation and genomic selection. The best phasing methods rely on both familial and linkage disequilibrium (LD) information. With whole-genome sequence (WGS) data, relatively small samples of reference individuals are generally sequenced due to prohibitive sequencing costs, thus only a limited amount of familial information is available. However, reference individuals have many relatives that have been genotyped (at lower density). The goal of our study was to improve phasing of WGS data by integrating familial information from haplotypes that were obtained from a larger genotyped dataset and to quantify its impact on imputation accuracy. Aligning a pre-phased WGS panel [~5 million single nucleotide polymorphisms (SNPs)], which is based on LD information only, to a 50k SNP array that is phased with both LD and familial information (called scaffold) resulted in correctly assigning parental origin for 99.62% of the WGS SNPs, their phase being determined unambiguously based on parental genotypes. Without using the 50k haplotypes as scaffold, that value dropped as expected to 50%. Correctly phased segments were on average longer after alignment...Continue Reading

References

Mar 20, 2001·American Journal of Human Genetics·M StephensP Donnelly
Dec 4, 2001·Nature Genetics·Gonçalo R AbecasisLon R Cardon
Dec 18, 2001·Genetics, Selection, Evolution : GSE·T H Meuwissen, M E Goddard
May 7, 2002·American Journal of Human Genetics·Dajun Qian, Lars Beckmann
Feb 24, 2006·PLoS Biology·Benjamin F VoightJonathan K Pritchard
Dec 18, 2008·BMC Bioinformatics·Olivier DelaneauJean-François Zagury
Jan 24, 2009·Nature Genetics·Augustine KongKari Stefansson
Mar 4, 2011·Genetics, Selection, Evolution : GSE·Paul M VanRadenKent A Weigel
Mar 11, 2011·Genetics, Selection, Evolution : GSE·John M HickeyJulius H J van der Werf
Jun 10, 2011·Bioinformatics·Petr DanecekUNKNOWN 1000 Genomes Project Analysis Group
Dec 6, 2011·Nature Methods·Olivier DelaneauJean-François Zagury
Dec 28, 2012·Nature Methods·Olivier DelaneauJonathan Marchini
Feb 15, 2013·Genetics, Selection, Evolution : GSE·Hubert PauschRuedi Fries
Jan 21, 2014·Cell·Richard MottJonathan Flint
Jun 18, 2014·BMC Genomics·Mehdi SargolzaeiFlavio S Schenkel
Feb 6, 2015·Nature Communications·Olivier DelaneauUNKNOWN 1000 Genomes Project Consortium
Aug 2, 2015·Genetics, Selection, Evolution : GSE·Beatriz Cd CuyabanoMogens S Lund
Nov 26, 2015·BMC Genomics·Amanda J ChamberlainMichael E Goddard
Jul 5, 2016·Nature Genetics·Robert W DaviesRichard Mott
Aug 6, 2016·Genetics, Selection, Evolution : GSE·Claudia A SevillanoMario P L Calus

❮ Previous
Next ❯

Citations

Dec 24, 2017·Genetics, Selection, Evolution : GSE·Marina SoléTom Druet
Jul 19, 2019·Frontiers in Genetics·Pierre FauxTom Druet

❮ Previous
Next ❯

Methods Mentioned

BETA
genotyping

Software Mentioned

DAGPHASE
AlphaPhase
SHAPEIT2
FImpute
Beagle
LINKPHASE3
VCFtools
GEN
findhap
Impute2

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.