Integrating RNA-Seq with GWAS reveals novel insights into the molecular mechanism underpinning ketosis in cattle

dc.contributor.authorYan, Ze
dc.contributor.authorHuang, Hetian
dc.contributor.authorFreebern, Ellen
dc.contributor.authorSantos, Daniel J. A.
dc.contributor.authorDai, Dongmei
dc.contributor.authorSi, Jingfang
dc.contributor.authorMa, Chong
dc.contributor.authorCao, Jie
dc.contributor.authorGuo, Gang
dc.contributor.authorLiu, George E.
dc.contributor.authorMa, Li
dc.contributor.authorFang, Lingzhao
dc.contributor.authorZhang, Yi
dc.date.accessioned2021-03-12T18:08:11Z
dc.date.available2021-03-12T18:08:11Z
dc.date.issued2020-07-17
dc.description.abstractKetosis is a common metabolic disease during the transition period in dairy cattle, resulting in long-term economic loss to the dairy industry worldwide. While genetic selection of resistance to ketosis has been adopted by many countries, the genetic and biological basis underlying ketosis is poorly understood. We collected a total of 24 blood samples from 12 Holstein cows, including 4 healthy and 8 ketosis-diagnosed ones, before (2 weeks) and after (5 days) calving, respectively. We then generated RNA-Sequencing (RNA-Seq) data and seven blood biochemical indicators (bio-indicators) from leukocytes and plasma in each of these samples, respectively. By employing a weighted gene co-expression network analysis (WGCNA), we detected that 4 out of 16 gene-modules, which were significantly engaged in lipid metabolism and immune responses, were transcriptionally (FDR < 0.05) correlated with postpartum ketosis and several bio-indicators (e.g., high-density lipoprotein and low-density lipoprotein). By conducting genome-wide association signal (GWAS) enrichment analysis among six common health traits (ketosis, mastitis, displaced abomasum, metritis, hypocalcemia and livability), we found that 4 out of 16 modules were genetically (FDR < 0.05) associated with ketosis, among which three were correlated with postpartum ketosis based on WGCNA. We further identified five candidate genes for ketosis, including GRINA, MAF1, MAFA, C14H8orf82 and RECQL4. Our phenome-wide association analysis (Phe-WAS) demonstrated that human orthologues of these candidate genes were also significantly associated with many metabolic, endocrine, and immune traits in humans. For instance, MAFA, which is involved in insulin secretion, glucose response, and transcriptional regulation, showed a significantly higher association with metabolic and endocrine traits compared to other types of traits in humans. In summary, our study provides novel insights into the molecular mechanism underlying ketosis in cattle, and highlights that an integrative analysis of omics data and cross-species mapping are promising for illustrating the genetic architecture underpinning complex traits.en_US
dc.description.urihttps://doi.org/10.1186/s12864-020-06909-z
dc.identifierhttps://doi.org/10.13016/9tru-q1dl
dc.identifier.citationYan, Z., Huang, H., Freebern, E. et al. Integrating RNA-Seq with GWAS reveals novel insights into the molecular mechanism underpinning ketosis in cattle. BMC Genomics 21, 489 (2020).en_US
dc.identifier.urihttp://hdl.handle.net/1903/26925
dc.language.isoen_USen_US
dc.publisherSpringer Natureen_US
dc.relation.isAvailableAtCollege of Agriculture & Natural Resourcesen_us
dc.relation.isAvailableAtAnimal & Avian Sciencesen_us
dc.relation.isAvailableAtDigital Repository at the University of Marylanden_us
dc.relation.isAvailableAtUniversity of Maryland (College Park, MD)en_us
dc.subjectGWASen_US
dc.subjectHolsteinen_US
dc.subjectKetosisen_US
dc.subjectRNA-Seqen_US
dc.subjectPhe-WASen_US
dc.subjectWGCNAen_US
dc.titleIntegrating RNA-Seq with GWAS reveals novel insights into the molecular mechanism underpinning ketosis in cattleen_US
dc.typeArticleen_US

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
s12864-020-06909-z.pdf
Size:
2.55 MB
Format:
Adobe Portable Document Format
Description: