Sex-Specific Parent-of-Origin Allelic Expression in the Mouse Brain

Abstract

Genomic imprinting results in preferential gene expression from paternally versus maternally inherited chromosomes. We used a genome-wide approach to uncover sex-specific parent-of-origin allelic effects in the adult mouse brain. Our study identified preferential selection of the maternally inherited X chromosome in glutamatergic neurons of the female cortex. Moreover, analysis of the cortex and hypothalamus identified 347 autosomal genes with sex-specific imprinting features. In the hypothalamus, sex-specific imprinted genes were mostly found in females, which suggests parental influence over the hypothalamic function of daughters. We show that interleukin-18, a gene linked to diseases with sex-specific prevalence, is subject to complex, regional, and sex-specific parental effects in the brain. Parent-of-origin effects thus provide new avenues for investigation of sexual dimorphism in brain function and disease.

Non-conflict theories for the evolution of genomic imprinting

“…Once again, mathematical modelling confirms the verbal reasoning, but the hypothesis has been criticized as predicting sexually dimorphic imprinting, for which we are yet to discover a completely convincing example (but see Hager et al, 2008;Gregg et al, 2010). Nevertheless, gene expression differs between males and females for many organisms (Ellegren and Parsch, 2007) and it would be surprising if such differences did not apply to at least some loci subject to imprinting.…”

“…Cases of transposableelement insertion impacting methylation status and likely giving rise to de novo imprinting have been cited; hence, TEs clearly can be involved in some cases; however, this observation does not mean that genomic defence of TE insertion is tied to the evolution of imprinting. Several models posit the existence of sex-specific genomic imprinting, but there have been no reports pinning down the quantitative-trait loci (QTLs) reported by Hager et al (2008) or confirming the findings of Gregg et al (2010), and efforts using RNAseq in reciprocal F1 mouse brain and placenta find no cases of sexspecific genomic imprinting (Wang and Clark, unpublished). The maternal-fetal co-adaptation hypothesis is appealing because of the significant number of imprinted genes whose expression levels seem to be highly coordinated in the mother and fetus and seem to be crucial for placental function.…”

Effects of maternal nutrition on the expression of genomic imprinted genes in ovine fetuses

“…These 80 contain potential candidate imprinted genes in the sheep for future studies. Recent NGS studies identified more than 1,300 imprinted loci in mouse brain [36,37]; however, most were due to false positives [18]. To avoid such problems, we used the combined list of imprinted genes from all studied species to conservatively guide our data-mining.…”

Male and female differential reproductive rate could explain parental transmission asymmetry of mutation origin in Hirschsprung disease

“…A sex-specific genomic imprinting has been found to be far more frequent than commonly assumed in mouse brain. 19 However, this hypothesis was unlikely for HSCR as RET expression is biallelic in the gut. 20 The question of a sperm-specific fitness explaining the parental transmission asymmetry, that is, a selective advantage for spermatozoids not carrying a RET CDS mutation, could also be raised, as the RET gene is known to play a crucial role in early spermatogenesis.…”