Including copy number variation in association studies to predict genotypic values.
The objective of this study was to investigate, both empirically and deterministically, the ability to explain genetic variation resulting from a copy number polymorphism (CNP) by including the CNP, either by its genotype or by a continuous derivation thereof, alone or together with a nearby single nucleotide polymorphism (SNP) in the model. This continuous measure of a CNP genotype could be a raw hybridization measurement, or a predicted CNP genotype. Results from simulations showed that the linkage disequilibrium (LD) between an SNP and CNP was lower than LD between two SNPs, due to the higher mutation rate at the CNP loci. The model R(2) values from analysing the simulated data were very similar to the R(2) values predicted with the deterministic formulae. Under the assumption that x copies at a CNP locus lead to the effect of x times the effect of 1 copy, including a continuous measure of a CNP locus in the model together with the genotype of a nearby SNP increased power to explain variation at the CNP locus, even when the continuous measure explained only 15% of the variation at the CNP locus.
Animal Breeding and Genomics Centre, Wageningen UR Livestock Research, 8200 AB, Lelystad, The Netherlands. mario.calus@wur.nl
M P L
MP
Calus
D J
DJ
DE Koning
C S
CS
Haley
D003198:Computer Simulation; D056915:DNA Copy Number Variations; D014644:Genetic Variation; D005838:Genotype; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide