Statistical Evidence for Imprinting from QTL or GWAS

In QTL mapping we can detect statistical evidence of imprinting in the contrast between the alternative heterozygotes (AB versus BA). For livestock species, the detection of imprinted QTL was introduced by Knott et al (1998). The methodology is an extension of the standard line cross model for outbred crosses introduced by Haley et al (1994). For further details on these models please see De Koning et al (2000, 2002). There are many reports of parent-of-origin QTL in pigs, reflecting the many divergent F2 crosses that exist for pigs as well as the interest raised by the initial publications by Nezer et al (1999). In poultry, where divergent F2 crosses are also very abundant, parent-of-origin effects were first reported by Tuiskula-Haavisto et al (2004). In general pedigrees, we can apply variance component models where the use of a gametic relationship matrix facilitates the estimation of separate maternal and paternal variance components (Rowe et al, 2009). In all these analyses empirical thresholds are required to prevent the detection of spurious parent-of-origin effects.  In GWAS studies, commonly only a single generation is genotyped and there is no opportunity to estimate parent-of-origin effects.  In livestock we are in the fortunate circumstance that we have extensive pedigree information and by combining haplotyping and imputation approaches we may be able to get a handle on parent-of-origin effects. Also for genome-wide prediction we propose the use of haplotypic IBD matrices in favor of genotypic IBS matrices.  The use of haplotypes in genomic prediction also accommodates different cross breeding approaches. In order to quantify and understand the overall contribution to phenotypic variation we need to integrate the statistical evidence with that of allele specific gene expression data as well as bioinformatics approaches to identify the sequencing signatures of imprinted genes.

References

De Koning, D.J. et al 2002 Genetics161, no. 2:931-938.

De Koning, D.J et al 2000. PNAS 97, no. 14:7947-7950.

Haley C.S. et al 1994. Genetics136:1195-1207.

Knott, S.A. et al 1999. Genetics149, no. 2:1069-1080.

Nezer, C. et al. 1999. Nat.Genet.21, no. 2:155-156.

Rowe, S.J. et al 2009.Genet.Sel Evol.41:6.

Thomsen, H. et al 2004. J.Anim Sci.82, no. 8:2213-2228.

Tuiskula-Haavisto M. et al 2004. Genet.Res. 84:57-66.