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)

Jingyuan Yang

April 9th 2008

Statistical Genetics Journal Club

Apparent POE Caused by Maternal Effect

SS LL

SL

LL SS

SS SSLLLL

SL

LS

LS

POE caused by genomic imprinting

Apparent POE caused by maternal effect

Genetic Model

Genotype A Mother An offspring

EffectFrequenc

yEffect

LL p2

LS2pq

SL

SS q2

2/)SSLL(LL mmmm a

2/)SSLL(SS mmmm a

2/)SSLL(

2/)SLLS(

mm

mmm

d

2/)SSLL(LLo a

2/)SSLL(LLo a

2/)SSLL(LSoo id

2/)SSLL(SLoo id

2/)SSLL(2/)SLLS(o d 2/)SLLS(o i

valuesgenotypic effect-direct the are SS ,SL ,LS ,LL

valuesgenotypic effect-maternal the are SS ,SL ,LS ,LL mmmm

Genetic Model (Cont.)

I. Parental Expression

• Maternal Expression

• Paternal Expression

In both cases:

Patterns of POEs

SSSL ,LSLL

SSLS ,SLLL

02/2/)( )SSLL(SLLSod

oo )/2LSSL()/2SSLL( ia

oo )SLLS()SSLL( ia 2/2/

II. Polar Dominance• Polar Overdominance

• Polar Underdominance

III.Bipolar Dominance

o o

o

- orSLLS or SLLS

)SSLL(SLLS

ii

d

2/)(2/)(

2/2/)(

SSLSLLSL or SSSLLLLS

SSLSLLSL or SSSLLLLS

SSLL ,SLLS

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

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

Thank you!