Parental Phasing Study Identified Lineage-Specific Variants Associated with Gene Expression and Epigenetic Modifications in European–Chinese Hybrid Pigs

Understanding how hybrids integrate lineage-specific regulatory variants at the haplotype level is crucial for elucidating the genetic basis of heterosis in livestock. In this study, we established three crossbred pig families derived from distant genetic lineages and systematically identified varia...

Full description

Saved in:
Bibliographic Details
Main Authors: Chenyu Li, Mei Ge, Keren Long, Ziyin Han, Jing Li, Mingzhou Li, Zhiyan Zhang
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Animals
Subjects:
Online Access:https://www.mdpi.com/2076-2615/15/10/1494
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849327484937437184
author Chenyu Li
Mei Ge
Keren Long
Ziyin Han
Jing Li
Mingzhou Li
Zhiyan Zhang
author_facet Chenyu Li
Mei Ge
Keren Long
Ziyin Han
Jing Li
Mingzhou Li
Zhiyan Zhang
author_sort Chenyu Li
collection DOAJ
description Understanding how hybrids integrate lineage-specific regulatory variants at the haplotype level is crucial for elucidating the genetic basis of heterosis in livestock. In this study, we established three crossbred pig families derived from distant genetic lineages and systematically identified variants from different lineages, including single nucleotide polymorphisms (SNPs) and structural variations (SVs). At the phase level, we quantitatively analyzed gene expression, four histone modifications (H3K4me3, H3K27ac, H3K4me1, and H3K27me3), and the binding strength of transcription factor (CTCF) in backfat (BF) and longissimus dorsi (LD) muscle. By colocalization analysis of phased genetic variants with phased gene expression levels and with phased epigenetic modifications, we identified 18,670 expression quantitative trait loci (eQTL) (FDR < 0.05) and 8,652 epigenetic modification quantitative trait loci (epiQTL) (FDR < 0.05). The integration of eQTL and epiQTL allowed us to explore the potential regulatory mechanisms by which lineage-specific genetic variants simultaneously influence gene expression and epigenetic modifications. For example, we identified a Large White lineage-specific duplication (DUP) encompassing the <i>KIT</i> gene that was significantly associated with its promoter activity (FDR = 7.83 × 10<sup>−4</sup>) and expression levels (FDR = 9.03 × 10<sup>−4</sup>). Additionally, we found that a Duroc lineage-specific SNP located upstream of <i>AMIGO2</i> was significantly associated with a Duroc-specific H3K27ac peak (FDR = 0.035) and also showed a significant association with <i>AMIGO2</i> expression levels (FDR = 5.12 × 10<sup>−4</sup>). These findings underscore the importance of phased regulatory variants in shaping lineage-specific transcriptional programs and highlight how the haplotype-resolved integration of eQTL and epigenetic signals can reveal the mechanistic underpinnings of hybrid regulatory architecture. Our results offer insights for molecular marker development in precision pig breeding.
format Article
id doaj-art-420f4bbf46464dd0a73da1c0aacc0b9c
institution Kabale University
issn 2076-2615
language English
publishDate 2025-05-01
publisher MDPI AG
record_format Article
series Animals
spelling doaj-art-420f4bbf46464dd0a73da1c0aacc0b9c2025-08-20T03:47:52ZengMDPI AGAnimals2076-26152025-05-011510149410.3390/ani15101494Parental Phasing Study Identified Lineage-Specific Variants Associated with Gene Expression and Epigenetic Modifications in European–Chinese Hybrid PigsChenyu Li0Mei Ge1Keren Long2Ziyin Han3Jing Li4Mingzhou Li5Zhiyan Zhang6National Key Laboratory for Swine Genetic Improvement and Germplasm innovation Technology, Jiangxi Agricultural University, Nanchang 330045, ChinaNational Key Laboratory for Swine Genetic Improvement and Germplasm innovation Technology, Jiangxi Agricultural University, Nanchang 330045, ChinaState Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaState Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaState Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaState Key Laboratory of Swine and Poultry Breeding Industry, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, ChinaNational Key Laboratory for Swine Genetic Improvement and Germplasm innovation Technology, Jiangxi Agricultural University, Nanchang 330045, ChinaUnderstanding how hybrids integrate lineage-specific regulatory variants at the haplotype level is crucial for elucidating the genetic basis of heterosis in livestock. In this study, we established three crossbred pig families derived from distant genetic lineages and systematically identified variants from different lineages, including single nucleotide polymorphisms (SNPs) and structural variations (SVs). At the phase level, we quantitatively analyzed gene expression, four histone modifications (H3K4me3, H3K27ac, H3K4me1, and H3K27me3), and the binding strength of transcription factor (CTCF) in backfat (BF) and longissimus dorsi (LD) muscle. By colocalization analysis of phased genetic variants with phased gene expression levels and with phased epigenetic modifications, we identified 18,670 expression quantitative trait loci (eQTL) (FDR < 0.05) and 8,652 epigenetic modification quantitative trait loci (epiQTL) (FDR < 0.05). The integration of eQTL and epiQTL allowed us to explore the potential regulatory mechanisms by which lineage-specific genetic variants simultaneously influence gene expression and epigenetic modifications. For example, we identified a Large White lineage-specific duplication (DUP) encompassing the <i>KIT</i> gene that was significantly associated with its promoter activity (FDR = 7.83 × 10<sup>−4</sup>) and expression levels (FDR = 9.03 × 10<sup>−4</sup>). Additionally, we found that a Duroc lineage-specific SNP located upstream of <i>AMIGO2</i> was significantly associated with a Duroc-specific H3K27ac peak (FDR = 0.035) and also showed a significant association with <i>AMIGO2</i> expression levels (FDR = 5.12 × 10<sup>−4</sup>). These findings underscore the importance of phased regulatory variants in shaping lineage-specific transcriptional programs and highlight how the haplotype-resolved integration of eQTL and epigenetic signals can reveal the mechanistic underpinnings of hybrid regulatory architecture. Our results offer insights for molecular marker development in precision pig breeding.https://www.mdpi.com/2076-2615/15/10/1494lineage-specific genetic variantsphased gene expressionphased epigenetic regulationhybrid pigs
spellingShingle Chenyu Li
Mei Ge
Keren Long
Ziyin Han
Jing Li
Mingzhou Li
Zhiyan Zhang
Parental Phasing Study Identified Lineage-Specific Variants Associated with Gene Expression and Epigenetic Modifications in European–Chinese Hybrid Pigs
Animals
lineage-specific genetic variants
phased gene expression
phased epigenetic regulation
hybrid pigs
title Parental Phasing Study Identified Lineage-Specific Variants Associated with Gene Expression and Epigenetic Modifications in European–Chinese Hybrid Pigs
title_full Parental Phasing Study Identified Lineage-Specific Variants Associated with Gene Expression and Epigenetic Modifications in European–Chinese Hybrid Pigs
title_fullStr Parental Phasing Study Identified Lineage-Specific Variants Associated with Gene Expression and Epigenetic Modifications in European–Chinese Hybrid Pigs
title_full_unstemmed Parental Phasing Study Identified Lineage-Specific Variants Associated with Gene Expression and Epigenetic Modifications in European–Chinese Hybrid Pigs
title_short Parental Phasing Study Identified Lineage-Specific Variants Associated with Gene Expression and Epigenetic Modifications in European–Chinese Hybrid Pigs
title_sort parental phasing study identified lineage specific variants associated with gene expression and epigenetic modifications in european chinese hybrid pigs
topic lineage-specific genetic variants
phased gene expression
phased epigenetic regulation
hybrid pigs
url https://www.mdpi.com/2076-2615/15/10/1494
work_keys_str_mv AT chenyuli parentalphasingstudyidentifiedlineagespecificvariantsassociatedwithgeneexpressionandepigeneticmodificationsineuropeanchinesehybridpigs
AT meige parentalphasingstudyidentifiedlineagespecificvariantsassociatedwithgeneexpressionandepigeneticmodificationsineuropeanchinesehybridpigs
AT kerenlong parentalphasingstudyidentifiedlineagespecificvariantsassociatedwithgeneexpressionandepigeneticmodificationsineuropeanchinesehybridpigs
AT ziyinhan parentalphasingstudyidentifiedlineagespecificvariantsassociatedwithgeneexpressionandepigeneticmodificationsineuropeanchinesehybridpigs
AT jingli parentalphasingstudyidentifiedlineagespecificvariantsassociatedwithgeneexpressionandepigeneticmodificationsineuropeanchinesehybridpigs
AT mingzhouli parentalphasingstudyidentifiedlineagespecificvariantsassociatedwithgeneexpressionandepigeneticmodificationsineuropeanchinesehybridpigs
AT zhiyanzhang parentalphasingstudyidentifiedlineagespecificvariantsassociatedwithgeneexpressionandepigeneticmodificationsineuropeanchinesehybridpigs