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Maternal Effects as the Cause of Parent-of-Origin Effects That Mimic Genomic Imprinting

Jingyuan Yang April 9 th 2008 Statistical Genetics Journal Club. 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 : 1755-1762 (March 2008). Apparent POE Caused by Maternal Effect. LL.

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Maternal Effects as the Cause of Parent-of-Origin Effects That Mimic Genomic Imprinting

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  1. Jingyuan Yang April 9th 2008 Statistical Genetics Journal Club 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: 1755-1762 (March 2008)

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

  3. Genetic Model

  4. Genetic Model (Cont.)

  5. Patterns of POEs • Parental Expression • Maternal Expression • Paternal Expression In both cases: • Polar Dominance • Polar Overdominance • Polar Underdominance • Bipolar Dominance

  6. 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 io = 0. Maternal Expression PaternalExpression BiopolarDominance PolarOverdominance

  7. General Result • 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.

  8. Genetic Model (Cont.)

  9. QTL Analysis • 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.

  10. Distinguish POEs and Apparent POEs • 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.

  11. Results

  12. Genotypic Values ofWtmge5.1 Offspring of heterozygous mothers All individuals

  13. Discussion • 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.

  14. Thank you!

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