Maternal Effects as the Cause of Parent-of-Origin Effects That Mimic Genomic Imprinting Reinmar Hager, James M. Cheverud and Jason B. Wolf Genetics 178 : (March 2008) Jingyuan Yang April 9 th 2008 Statistical Genetics Journal Club

Apparent POE Caused by Maternal Effect SS LL SL LL SS LL SL LS POE caused by genomic imprinting Apparent POE caused by maternal effect

Genetic Model Genotype A MotherAn offspring EffectFrequencyEffect LL p2p2 LS 2pq SL SS q2q2

Genetic Model (Cont.)

I.Parental Expression Maternal Expression Paternal Expression In both cases: Patterns of POEs II.Polar Dominance Polar Overdominance Polar Underdominance III.Bipolar Dominance

A Simple Numeric Example These patterns mimic POEs. But they are in fact caused by maternal effects or a combination of maternal and direct effects. Through all these patterns i o = 0. Maternal Expression Paternal Expression Biopolar Dominance Polar Overdominance

When performing an analysis using the parent-of-origin of alleles to look for genomic imprinting effects, significant positive results may actually be due to maternal effects. Just as maternal effects can mimic genomic imprinting effects, the opposite is also true; actual genomic imprinting effects can masquerade as maternal effects if an analysis is focused on maternal effects rather than genomic imprinting. One way to detect parent-of-origin effect with maternal effect being present is to restrict the analysis to offspring of heterozygous mothers, since maternal effects (due to either dominance or additive effects) do not contribute to differences between these offspring. General Result

Genetic Model (Cont.)

Strain: 382 F2 and 1632 F3 animals from an intercross between the two inbred mouse strains, large (LG/J) and small (SM/J). 13 Q-Traits: Mice were weighed weekly from 1 week of age to week 10 and weight gain from week 1 to 2, from week 1 to 6, and from week 3 to10. Genotyping: All F2 and F3 individuals were genotyped at 353 SNP loci across all 19 autosomes by Illumina. QTL analysis: Canonical correlation ( implemented by SAS proc cancorr) with direct effect parameters only. QTL Analysis

Strategy 1: Include genotype scores for both maternal genetic effects and imprinting effects in the model jointly and obtain the partial regression coefficient for each, holding the other constant. Strategy 2: Restrict the sample to offspring of heterozygous mothers as there is no maternal genetic effect variation among these offspring. Strategy 2 was applied to distinguish POEs and apparent POEs caused by maternal effect and strategy 1 was used to confirm the findings. Distinguish POEs and Apparent POEs

Results

Genotypic Values of Wtmge5.1 All individuals Offspring of heterozygous mothers

Genomic imprinting and maternal genetic effects can both generate the same phenotypic patterns that appear as parent-of- origin-dependent effects on offspring traits. Mistaking a maternal for an imprinting effect might lead to an inappropriate focus in follow-up studies. It was found that maternal effects affected traits at different stages in development from as early as week 1 body weight to as late as week 10. Distinction between genomic imprinting effects and maternal effects should be given in future studies aiming to analyze either of the two effects. Discussion

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