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WES-based linkage analysis, haplotype reconstruction and validation

CT Claudio Toma
AS Alex D. Shaw
RA Richard J. N. Allcock
AH Anna Heath
KP Kerrie D. Pierce
PM Philip B. Mitchell
PS Peter R. Schofield
JF Janice M. Fullerton
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Genotypes were called from aligned reads using samtools pileup and filtered to include haplotype-informative markers (HapMap CEU population) using LINKDATAGEN27. WES-derived genotypes were used to confirm familial relationships by pair-wise IBD using PLINK28, and also to perform haplotype phasing and linkage analysis in each family under both parametric and non-parametric models using Merlin29. Parameters for linkage analysis, as well as linkage results and SNV colocalization analyses are provided in Supplementary Material (Section 3).

Reconstructed haplotypes were visualized using HaploPainter30, and used to compare against inheritance of all rare potentially pathogenic variants in each family: those inconsistent with underlying haplotype (or where haplotype was uninformative) were validated by PCR and Sanger sequencing.

Copyright and License information: The Author(s) ©2018
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