# A comprehensive genome-wide scan for parent-of-origin expressed genes in the pig clarifies the conservation landscape of genomic imprinting

**Authors:** Mathilde Perret, Nathalie Iannuccelli, Sophie Leroux, Katia Fève, Patrice Dehais, Eva Jacomet, Jean-Noël Hubert, Carole Iampietro, Céline Vandecasteele, Sarah Maman-Haddad, Thomas Faraut, Laurence Liaubet, Agnès Bonnet, Cécile Donnadieu, Juliette Riquet, Julie Demars

PMC · DOI: 10.1186/s12711-026-01031-2 · Genetics, Selection, Evolution : GSE · 2026-03-09

## TL;DR

This study identifies many parent-of-origin expressed genes in pigs, showing that genomic imprinting is not highly conserved across species or tissues.

## Contribution

The study provides the most comprehensive map of imprinted genes in pigs, revealing weak conservation and new tissue-specific imprinted genes.

## Key findings

- 141 genes with strong parent-of-origin expression were identified in pigs.
- Most of these genes were previously unknown to be imprinted, and only 15% were shared across tissues.
- Novel imprinted genes related to neurodevelopment and fetal growth were discovered.

## Abstract

Genomic imprinting, a mechanism resulting in parent-of-origin expression of genes through epigenetic regulation, intersects with a broad range of biological fields, including evolution, molecular genetics and epigenetics, and determinism of complex traits. Although next generation sequencing technologies nowadays enable imprinted genes to be detected in a genome-wide manner, a wide spectrum of this phenomena is evaluated only in humans and rodents.

Here, we propose to map genes showing a parental expression imbalance in hypothalamus, muscle and placenta in piglets around birth using an extensive strategy that minimized biases and relied on reciprocal crosses, reconstruction of parental phases after imputation, and statistical analyses discriminating parent-of-origin from allele-specific expression. We detected 141 genes with strong to exclusive parental expression imbalance (ratio > 25:75). A large proportion (80%) of these genes have never been shown to exhibit parent-of-origin expression and a small proportion (15%) are shared by at least two tissues, suggesting an overall weak conservation landscape of genomic imprinting. Interestingly, we identified novel parent-of-origin expressed genes involved in neurodevelopmental (PREPL, Prolyl Endopeptidase Like) and fetal growth (FAM20B, Glycosaminoglycan Xylosylkinase, and POU6F2, POU Class 6 Homeobox 2) functions. In-depth analyses of specific loci highlighted specific imprinted isoforms of COPG2 (COPI Coat Complex Subunit Gamma 2) and confirmed livestock-specific imprinted genes such as the Zinc Finger Protein 300-like gene.

Altogether, our results provide an atlas of parent-of-origin expressed genes in the pig, making it the most documented species for genomic imprinting after humans and rodents. Our findings indicate weak conservation of this mechanism across species and tissues, suggesting a small number of core imprinted genes shared across eutherians and another imprinted genes that seem specific to species or tissues. These latter parent-of-origin expressed genes may have been subjected to evolutionary forces that have determine their imprinting status in either a livestock-specific or a tissue-specific manner.

The online version contains supplementary material available at 10.1186/s12711-026-01031-2.

## Linked entities

- **Genes:** PREPL (prolyl endopeptidase like) [NCBI Gene 9581], FAM20B (FAM20B glycosaminoglycan xylosylkinase) [NCBI Gene 9917], POU6F2 (POU class 6 homeobox 2) [NCBI Gene 11281], COPG2 (coat protein complex I subunit gamma 2) [NCBI Gene 26958]

## Full-text entities

- **Genes:** PODXL (podocalyxin like) [NCBI Gene 5420] {aka Gp200, PC, PCLP, PCLP-1, PDX, PODXL1}, GNAS (GNAS complex locus) [NCBI Gene 2778] {aka AHO, AIMAH1, C20orf45, GNAS1, GPSA, GSA}, FAM20B (FAM20B glycosaminoglycan xylosylkinase) [NCBI Gene 9917] {aka gxk1}, KBTBD6 (kelch repeat and BTB domain-containing protein 6) [NCBI Gene 100154105], PLAGL1 (PLAG1 like zinc finger 1) [NCBI Gene 5325] {aka LOT1, ZAC, ZAC1}, POU6F2 (POU class 6 homeobox 2) [NCBI Gene 100622573], POU6F2 (POU class 6 homeobox 2) [NCBI Gene 11281] {aka RPF-1, WT5, WTSL}, RENBP (renin binding protein) [NCBI Gene 396934] {aka RnBP}, PDE4DIP (phosphodiesterase 4D interacting protein) [NCBI Gene 9659] {aka CMYA2, MMGL}, HSD17B11 (hydroxysteroid 17-beta dehydrogenase 11) [NCBI Gene 51170] {aka 17-BETA-HSD11, 17-BETA-HSDXI, 17BHSD11, DHRS8, PAN1B, RETSDR2}, NAP1L5 (nucleosome assembly protein 1 like 5) [NCBI Gene 266812] {aka DRLM}, ZNF300 (zinc finger protein 300) [NCBI Gene 91975], AIRN (antisense of IGF2R non-protein coding RNA) [NCBI Gene 100271873] {aka AIR, IGF2R-AS, IGF2R-AS1, IGF2RAS, NCRNA00088}, TNKS (tankyrase) [NCBI Gene 8658] {aka ARTD5, PARP-5a, PARP5A, PARPL, TIN1, TINF1}, HM13 (histocompatibility minor 13) [NCBI Gene 81502] {aka H13, HM13-IT1, IMP1, IMPAS, IMPAS-1, MSTP086}, ZNF791 (zinc finger protein 791) [NCBI Gene 163049], LOC100520903 (zinc finger protein 300-like) [NCBI Gene 100520903], SLCO1A2 (solute carrier organic anion transporter family member 1A2) [NCBI Gene 397534] {aka OATP1A2, OATPA}, RNF216 (ring finger protein 216) [NCBI Gene 54476] {aka CAHH, TRIAD3, U7I1, UBCE7IP1, ZIN}, PREPL (prolyl endopeptidase like) [NCBI Gene 100526165], ZNF300 (zinc finger protein 300) [NCBI Gene 100621799], DCAF16 [NCBI Gene 100513295], COPG2 (COPI coat complex subunit gamma 2) [NCBI Gene 100515937], RBAK (RB associated KRAB zinc finger) [NCBI Gene 57786] {aka ZNF769}, ETNPPL (ethanolamine-phosphate phospho-lyase) [NCBI Gene 100519324], IGF2 (insulin like growth factor 2) [NCBI Gene 3481] {aka C11orf43, GRDF, IGF-II, PP9974, SRS3}, DDB1 (damage specific DNA binding protein 1) [NCBI Gene 100522239], TK2 (thymidine kinase 2) [NCBI Gene 7084] {aka MTDPS2, MTTK, PEOB3, SCA31, TK2-EXT}, PREPL (prolyl endopeptidase like) [NCBI Gene 9581] {aka CMS22}, BEGAIN (brain enriched guanylate kinase associated) [NCBI Gene 57596], SLA (Src like adaptor) [NCBI Gene 6503] {aka SLA1, SLAP}, GNAS-AS1 (GNAS antisense RNA 1) [NCBI Gene 149775] {aka GNAS-AS, GNAS1AS, GNASAS, NCRNA00075, NESP-AS, NESPAS}, KBTBD6 (kelch repeat and BTB domain containing 6) [NCBI Gene 89890], PEG10 (paternally expressed 10) [NCBI Gene 654416], CBR1 (carbonyl reductase 1) [NCBI Gene 873] {aka CBR, PG-9-KR, SDR21C1, hCBR1}, KCNQ1 (potassium voltage-gated channel subfamily Q member 1) [NCBI Gene 3784] {aka ATFB1, ATFB3, JLNS1, KCNA8, KCNA9, KVLQT1}, PEG3 (paternally expressed 3) [NCBI Gene 5178] {aka PW1, ZKSCAN22, ZNF904, ZSCAN24}, AOX1 (aldehyde oxidase 1) [NCBI Gene 100523701], KCNQ1OT1 (KCNQ1 opposite strand/antisense transcript 1) [NCBI Gene 10984] {aka KCNQ1-AS2, KCNQ10T1, Kncq1, KvDMR1, KvLQT1-AS, LIT1}, IGF2 (insulin like growth factor 2) [NCBI Gene 396916] {aka IGF-II}, IGF2R (insulin like growth factor 2 receptor) [NCBI Gene 3482] {aka CD222, CI-M6PR, CIMPR, M6P-R, M6P/IGF2R, MPR 300}, PLAGL1 (PLAG1 like zinc finger 1) [NCBI Gene 733596], MEST (mesoderm specific transcript) [NCBI Gene 4232] {aka PEG1}, FAM20B (FAM20B glycosaminoglycan xylosylkinase) [NCBI Gene 100523629], MEG3 (maternally expressed 3) [NCBI Gene 100144590] {aka GTL2}, RNF34 (ring finger protein 34) [NCBI Gene 80196] {aka CARP-1, CARP1, RFI, RIF, RIFF, hRFI}, COPG2IT1 (COPG2 imprinted transcript 1) [NCBI Gene 53844] {aka CIT1, COPG2AS, DKFZP761N09121, NCRNA00170}, COPG2 (coat protein complex I subunit gamma 2) [NCBI Gene 26958] {aka 2-COP, gamma-2-COP}
- **Diseases:** stunted growth (MESH:D006130), acute myeloid leukemia (MESH:D015470), imprinting disorders (MESH:C567357), Wilms' tumor (MESH:D009396), Beckwith-Wiedemann syndrome (MESH:D001506), embryonic lethality (MESH:D020964), POE (MESH:D063129), multisystem organ hypoplasia (MESH:D000092124)
- **Chemicals:** EDTA (MESH:D004492), sodium bisulfite (MESH:C009279), dA (MESH:C025953), agarose (MESH:D012685)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Canis lupus familiaris (dog, subspecies) [taxon 9615], Pan troglodytes (chimpanzee, species) [taxon 9598], Sus scrofa (pig, species) [taxon 9823], Ovis aries (domestic sheep, species) [taxon 9940], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Bos taurus (bovine, species) [taxon 9913], Equus caballus (domestic horse, species) [taxon 9796]
- **Mutations:** rs333817407, rs3476453296, rs700461902, rs3472187167, rs334493269, rs336408570, rs3473951016, rs3344933269, rs3472903225, rs339021210, rs326095797, rs3475266292, rs321963523, rs3474403860

## Full text

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## Figures

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Source: https://tomesphere.com/paper/PMC12969872