Identification and characterization of whole blood gene expression and splicing quantitative trait loci during early to mid-lactation of dairy cattle

Yongjie Tang; Jinning Zhang; Wenlong Li; Xueqin Liu; Siqian Chen; Siyuan Mi; Jinyan Yang; Jinyan Teng; Lingzhao Fang; Ying Yu

doi:10.1186/s12864-024-10346-7

Identification and characterization of whole blood gene expression and splicing quantitative trait loci during early to mid-lactation of dairy cattle

Yongjie Tang, Jinning Zhang, Wenlong Li, Xueqin Liu, Siqian Chen, Siyuan Mi, Jinyan Yang, Jinyan Teng, Lingzhao Fang^*, Ying Yu^*

^*Corresponding author for this work

Center for Quantitative Genetics and Genomics

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

2 Citations (Scopus)

Abstract

Background: Characterization of regulatory variants (e.g., gene expression quantitative trait loci, eQTL; gene splicing QTL, sQTL) is crucial for biologically interpreting molecular mechanisms underlying loci associated with complex traits. However, regulatory variants in dairy cattle, particularly in specific biological contexts (e.g., distinct lactation stages), remain largely unknown. In this study, we explored regulatory variants in whole blood samples collected during early to mid-lactation (22–150 days after calving) of 101 Holstein cows and analyzed them to decipher the regulatory mechanisms underlying complex traits in dairy cattle. Results: We identified 14,303 genes and 227,705 intron clusters expressed in the white blood cells of 101 cattle. The average heritability of gene expression and intron excision ratio explained by cis-SNPs is 0.28 ± 0.13 and 0.25 ± 0.13, respectively. We identified 23,485 SNP-gene expression pairs and 18,166 SNP-intron cluster pairs in dairy cattle during early to mid-lactation. Compared with the 2,380,457 cis-eQTLs reported to be present in blood in the Cattle Genotype-Tissue Expression atlas (CattleGTEx), only 6,114 cis-eQTLs (P < 0.05) were detected in the present study. By conducting colocalization analysis between cis-e/sQTL and the results of genome-wide association studies (GWAS) from four traits, we identified a cis-e/sQTL (rs109421300) of the DGAT1 gene that might be a key marker in early to mid-lactation for milk yield, fat yield, protein yield, and somatic cell score (PP4 > 0.6). Finally, transcriptome-wide association studies (TWAS) revealed certain genes (e.g., FAM83H and TBC1D17) whose expression in white blood cells was significantly (P < 0.05) associated with complex traits. Conclusions: This study investigated the genetic regulation of gene expression and alternative splicing in dairy cows during early to mid-lactation and provided new insights into the regulatory mechanisms underlying complex traits of economic importance.

Original language	English
Article number	445
Journal	BMC Genomics
Volume	25
Issue	1
Number of pages	13
ISSN	1471-2164
DOIs	https://doi.org/10.1186/s12864-024-10346-7
Publication status	Published - May 2024

Keywords

Colocalization
Early to mid-lactation period
eQTL
Holstein cows
sQTL
TWAS

Access to Document

10.1186/s12864-024-10346-7Licence: CC BY

Cite this

@article{c1c3a939b1ea42dd9d9c27efa837010c,

title = "Identification and characterization of whole blood gene expression and splicing quantitative trait loci during early to mid-lactation of dairy cattle",

abstract = "Background: Characterization of regulatory variants (e.g., gene expression quantitative trait loci, eQTL; gene splicing QTL, sQTL) is crucial for biologically interpreting molecular mechanisms underlying loci associated with complex traits. However, regulatory variants in dairy cattle, particularly in specific biological contexts (e.g., distinct lactation stages), remain largely unknown. In this study, we explored regulatory variants in whole blood samples collected during early to mid-lactation (22–150 days after calving) of 101 Holstein cows and analyzed them to decipher the regulatory mechanisms underlying complex traits in dairy cattle. Results: We identified 14,303 genes and 227,705 intron clusters expressed in the white blood cells of 101 cattle. The average heritability of gene expression and intron excision ratio explained by cis-SNPs is 0.28 ± 0.13 and 0.25 ± 0.13, respectively. We identified 23,485 SNP-gene expression pairs and 18,166 SNP-intron cluster pairs in dairy cattle during early to mid-lactation. Compared with the 2,380,457 cis-eQTLs reported to be present in blood in the Cattle Genotype-Tissue Expression atlas (CattleGTEx), only 6,114 cis-eQTLs (P < 0.05) were detected in the present study. By conducting colocalization analysis between cis-e/sQTL and the results of genome-wide association studies (GWAS) from four traits, we identified a cis-e/sQTL (rs109421300) of the DGAT1 gene that might be a key marker in early to mid-lactation for milk yield, fat yield, protein yield, and somatic cell score (PP4 > 0.6). Finally, transcriptome-wide association studies (TWAS) revealed certain genes (e.g., FAM83H and TBC1D17) whose expression in white blood cells was significantly (P < 0.05) associated with complex traits. Conclusions: This study investigated the genetic regulation of gene expression and alternative splicing in dairy cows during early to mid-lactation and provided new insights into the regulatory mechanisms underlying complex traits of economic importance.",

keywords = "Colocalization, Early to mid-lactation period, eQTL, Holstein cows, sQTL, TWAS",

author = "Yongjie Tang and Jinning Zhang and Wenlong Li and Xueqin Liu and Siqian Chen and Siyuan Mi and Jinyan Yang and Jinyan Teng and Lingzhao Fang and Ying Yu",

year = "2024",

month = may,

doi = "10.1186/s12864-024-10346-7",

language = "English",

volume = "25",

journal = "BMC Genomics",

issn = "1471-2164",

publisher = "BioMed Central",

number = "1",

}

Identification and characterization of whole blood gene expression and splicing quantitative trait loci during early to mid-lactation of dairy cattle. / Tang, Yongjie; Zhang, Jinning; Li, Wenlong et al.
In: BMC Genomics, Vol. 25, No. 1, 445, 05.2024.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Identification and characterization of whole blood gene expression and splicing quantitative trait loci during early to mid-lactation of dairy cattle

AU - Tang, Yongjie

AU - Zhang, Jinning

AU - Li, Wenlong

AU - Liu, Xueqin

AU - Chen, Siqian

AU - Mi, Siyuan

AU - Yang, Jinyan

AU - Teng, Jinyan

AU - Fang, Lingzhao

AU - Yu, Ying

PY - 2024/5

Y1 - 2024/5

N2 - Background: Characterization of regulatory variants (e.g., gene expression quantitative trait loci, eQTL; gene splicing QTL, sQTL) is crucial for biologically interpreting molecular mechanisms underlying loci associated with complex traits. However, regulatory variants in dairy cattle, particularly in specific biological contexts (e.g., distinct lactation stages), remain largely unknown. In this study, we explored regulatory variants in whole blood samples collected during early to mid-lactation (22–150 days after calving) of 101 Holstein cows and analyzed them to decipher the regulatory mechanisms underlying complex traits in dairy cattle. Results: We identified 14,303 genes and 227,705 intron clusters expressed in the white blood cells of 101 cattle. The average heritability of gene expression and intron excision ratio explained by cis-SNPs is 0.28 ± 0.13 and 0.25 ± 0.13, respectively. We identified 23,485 SNP-gene expression pairs and 18,166 SNP-intron cluster pairs in dairy cattle during early to mid-lactation. Compared with the 2,380,457 cis-eQTLs reported to be present in blood in the Cattle Genotype-Tissue Expression atlas (CattleGTEx), only 6,114 cis-eQTLs (P < 0.05) were detected in the present study. By conducting colocalization analysis between cis-e/sQTL and the results of genome-wide association studies (GWAS) from four traits, we identified a cis-e/sQTL (rs109421300) of the DGAT1 gene that might be a key marker in early to mid-lactation for milk yield, fat yield, protein yield, and somatic cell score (PP4 > 0.6). Finally, transcriptome-wide association studies (TWAS) revealed certain genes (e.g., FAM83H and TBC1D17) whose expression in white blood cells was significantly (P < 0.05) associated with complex traits. Conclusions: This study investigated the genetic regulation of gene expression and alternative splicing in dairy cows during early to mid-lactation and provided new insights into the regulatory mechanisms underlying complex traits of economic importance.

AB - Background: Characterization of regulatory variants (e.g., gene expression quantitative trait loci, eQTL; gene splicing QTL, sQTL) is crucial for biologically interpreting molecular mechanisms underlying loci associated with complex traits. However, regulatory variants in dairy cattle, particularly in specific biological contexts (e.g., distinct lactation stages), remain largely unknown. In this study, we explored regulatory variants in whole blood samples collected during early to mid-lactation (22–150 days after calving) of 101 Holstein cows and analyzed them to decipher the regulatory mechanisms underlying complex traits in dairy cattle. Results: We identified 14,303 genes and 227,705 intron clusters expressed in the white blood cells of 101 cattle. The average heritability of gene expression and intron excision ratio explained by cis-SNPs is 0.28 ± 0.13 and 0.25 ± 0.13, respectively. We identified 23,485 SNP-gene expression pairs and 18,166 SNP-intron cluster pairs in dairy cattle during early to mid-lactation. Compared with the 2,380,457 cis-eQTLs reported to be present in blood in the Cattle Genotype-Tissue Expression atlas (CattleGTEx), only 6,114 cis-eQTLs (P < 0.05) were detected in the present study. By conducting colocalization analysis between cis-e/sQTL and the results of genome-wide association studies (GWAS) from four traits, we identified a cis-e/sQTL (rs109421300) of the DGAT1 gene that might be a key marker in early to mid-lactation for milk yield, fat yield, protein yield, and somatic cell score (PP4 > 0.6). Finally, transcriptome-wide association studies (TWAS) revealed certain genes (e.g., FAM83H and TBC1D17) whose expression in white blood cells was significantly (P < 0.05) associated with complex traits. Conclusions: This study investigated the genetic regulation of gene expression and alternative splicing in dairy cows during early to mid-lactation and provided new insights into the regulatory mechanisms underlying complex traits of economic importance.

KW - Colocalization

KW - Early to mid-lactation period

KW - eQTL

KW - Holstein cows

KW - sQTL

KW - TWAS

UR - http://www.scopus.com/inward/record.url?scp=85192174662&partnerID=8YFLogxK

U2 - 10.1186/s12864-024-10346-7

DO - 10.1186/s12864-024-10346-7

M3 - Journal article

C2 - 38711039

AN - SCOPUS:85192174662

SN - 1471-2164

VL - 25

JO - BMC Genomics

JF - BMC Genomics

IS - 1

M1 - 445

ER -

Identification and characterization of whole blood gene expression and splicing quantitative trait loci during early to mid-lactation of dairy cattle

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this