Research Article
BibTex RIS Cite

Süt Sığırlarında Ketozis Direnci için Gen Zenginleştirme ve Yolak Analizi: GWAS Tabanlı Bir Yaklaşım

Year 2024, Volume: 11 Issue: 4, 1014 - 1022, 12.10.2024
https://doi.org/10.30910/turkjans.1522944

Abstract

Süt sığırlarında ketozis, geç gebelik döneminden erken laktasyon dönemine geçişte ortaya çıkan yaygın bir metabolik bozukluktur. Bu durum, enerji alımı ile harcaması arasındaki dengesizlikten kaynaklanır ve keton cisimciklerinin aşırı birikimine yol açar. Ketozis, sığır sağlığını ve verimliliğini önemli ölçüde etkileyebilir. Genom araştırmalarındaki, özellikle de genom boyu dizileme analizleri (GWAS) gibi son gelişmeler, ketozis direncine katkıda bulunan genetik faktörleri keşfetme fırsatı sunmaktadır.
Bu araştırmanın amacı, süt sığırlarında ketozis direnci ile ilişkili potansiyel fonksiyonel aday gen yolaklarını belirlemek için var olan GWAS verilerini gen zenginleşmesi analizi kullanarak kapsamlı bir şekilde incelemek ve analiz etmektir. Bu çalışmada yedi farklı çalışmadan elde edilen verileri incelenmiş ve filtreleme sonrası 640 tekrarsız gen elde edilmiştir. Tanımlanan genlerin insan homologları ile Enrichr adlı çevrimiçi gen anotasyon aracı kullanılarak yolak analizi yapılmıştır. Bulgularımız, trigliserit metabolizmasının düzenlenmesini ve ketozis sırasında metabolik dengenin korunmasında şilomikronların rolünü ve asilgliserol homeostaz yolaklarını ön plana çıkarmaktadır. Ayrıca, immün yanıt yolaklarının ketozis ile ilişkili genlerle bağlantılı olduğu bulunmuştur, bu da metabolik yolaklar ve immün yolaklar arasındaki karmaşık etkileşimlere dair bilgiler sunmaktadır.
Bu çalışma, süt sığırlarında metabolik sağlığı ve verimliliği arttırmayı amaçlayan yetiştirme stratejilerinin geliştirilmesinde genetik faktörlerin anlaşılmasının önemini vurgulamaktadır. Gelecek araştırmalar, bu aday genlerin doğrulanmasına ve mekanistik rollerinin incelenmesine odaklanarak, hedefe yönelik müdahaleleri kolaylaştırmalı ve süt sürülerinde ketozis direncini artırmalıdır.

References

  • Al Odaib A, Shneider BL, Bennett MJ, Pober BR, Reyes-Mugica M, Friedman AL, Suchy FJ, Rinaldo P (1998) A defect in the transport of long-chain fatty acids associated with acute liver failure. New England Journal of Medicine 339:1752–1757
  • Bergman EN (1971) Hyperketonemia-ketogenesis and ketone body metabolism. Journal of dairy science 54:936–948
  • Carrier J, Stewart S, Godden S, Fetrow J, Rapnicki P (2004) Evaluation and Use of Three Cowside Tests for Detection of Subclinical Ketosis in Early Postpartum Cows. Journal of Dairy Science 87:3725–3735. https://doi.org/10.3168/jds.S0022-0302(04)73511-0
  • David Baird G (1982) Primary Ketosis in the High-Producing Dairy Cow: Clinical and Subclinical Disorders, Treatment, Prevention, and Outlook. Journal of Dairy Science 65:1–10. https://doi.org/https://doi.org/10.3168/jds.S0022-0302(82)82146-2
  • Evangelista JE, Xie Z, Marino GB, Nguyen N, Clarke DJB, Ma’ayan A (2023) Enrichr-KG: bridging enrichment analysis across multiple libraries. Nucleic Acids Research 51:W168–W179. https://doi.org/10.1093/nar/gkad393
  • Faruk S Al, Park B, Ha S, Lee S, Mamuad LL, Cho Y (2020) Comparative study on different field tests of ketosis using blood , milk , and urine in dairy cattle. Veterinární Medicína 65:199–206. https://doi.org/10.17221/69/2019-VETMED
  • Freebern E, Santos DJA, Fang L, Jiang J, Parker Gaddis KL, Liu GE, Vanraden PM, Maltecca C, Cole JB, Ma L (2020) GWAS and fine-mapping of livability and six disease traits in Holstein cattle. BMC Genomics 21:1–11. https://doi.org/10.1186/s12864-020-6461-z
  • Gaddis KLP, Jr JHM, Clay JS, Wolfe CW (2018) Genome-wide association study for ketosis in US Jerseys using producer-recorded data. Journal of Dairy Science 101:413–424. https://doi.org/10.3168/jds.2017-13383
  • Giammanco A, Cefalù AB, Noto D, Averna MR (2015) The pathophysiology of intestinal lipoprotein production. Frontiers in physiology 6:61
  • Hasin Y, Seldin M, Lusis A (2017) Multi-omics approaches to disease. Genome Biology 18:83. https://doi.org/10.1186/s13059-017-1215-1
  • Houten SM, Wanders RJA (2010) A general introduction to the biochemistry of mitochondrial fatty acid β-oxidation. Journal of inherited metabolic disease 33:469–477
  • Huang H, Cao J, Hanif Q, Wang Y, Yu Y, Zhang S, Zhang Y (2019) Genome-wide association study identifies energy metabolism genes for resistance to ketosis in Chinese Holstein cattle. Animal Genetics 50:376–380. https://doi.org/10.1111/age.12802
  • Krebs H (1960) Biochemical aspects of ketosis. Içinde: Proceedings of the Royal Society of Medicine. SAGE Publications, ss 71–80
  • Kroezen V, Schenkel FS, Miglior F, Baes CF, Squires EJ (2018) Candidate gene association analyses for ketosis resistance in Holsteins. Journal of Dairy Science 101:5240–5249. https://doi.org/10.3168/jds.2017-13374
  • Leroy JLMR, Van Soom A, Opsomer G, Bols PEJ (2008) The consequences of metabolic changes in high-yielding dairy cows on oocyte and embryo quality*. Animal 2:1120–1127. https://doi.org/https://doi.org/10.1017/S1751731108002383
  • Littledike ET, Young JW, Beitz DC (1981) Common Metabolic Diseases of Cattle: Ketosis, Milk Fever, Grass Tetany, and Downer Cow Complex1. Journal of Dairy Science 64:1465–1482. https://doi.org/https://doi.org/10.3168/jds.S0022-0302(81)82715-4
  • McGarry JD, Foster DW (1972) Regulation of ketogenesis and clinical aspects of the ketotic state. Metabolism 21:471–489. https://doi.org/https://doi.org/10.1016/0026-0495(72)90059-5
  • McSherry BJ, Maplesden DC, Branion HD (1960) Ketosis in Cattle-a Review. The Canadian veterinary journal = La revue veterinaire canadienne 1:208–213
  • Nayeri S, Schenkel F, Fleming A, Kroezen V, Sargolzaei M, Baes C, Cánovas A, Squires J, Miglior F (2019) Genome-wide association analysis for β-hydroxybutyrate concentration in Milk in Holstein dairy cattle. BMC genetics 20:1–17
  • Nielsen NI, Ingvartsen KL (2004) Propylene glycol for dairy cows: A review of the metabolism of propylene glycol and its effects on physiological parameters, feed intake, milk production and risk of ketosis. Animal Feed Science and Technology 115:191–213
  • Oetzel GR, Mcguirk SM (2008) Evaluation of a Hand-Held Meter for Cowside Evaluation of Blood Beta- Hydroxybutyrate and Glucose Concentrations in Dairy Cows. 41:53706
  • Ofori EK (2023) Lipids and Lipoprotein Metabolism, Dyslipidemias, and Management. Içinde: Current Trends in the Diagnosis and Management of Metabolic Disorders. CRC Press, ss 150–170
  • Packard CJ, Boren J, Taskinen M-R (2020) Causes and consequences of hypertriglyceridemia. Frontiers in endocrinology 11:252
  • Pryce JE, Parker Gaddis KL, Koeck A, Bastin C, Abdelsayed M, Gengler N, Miglior F, Heringstad B, Egger-Danner C, Stock KF, Bradley AJ, Cole JB (2016) Invited review: Opportunities for genetic improvement of metabolic diseases. Journal of Dairy Science 99:6855–6873. https://doi.org/10.3168/jds.2016-10854
  • Sakai T, Hayakawa T, Hamakawa M, Ogura K, Kubo S (1993) Therapeutic Effects of Simultaneous Use of Glucose and Insulin in Ketotic Dairy Cows. Journal of Dairy Science 76:109–114. https://doi.org/https://doi.org/10.3168/jds.S0022-0302(93)77329-4
  • Satomura A, Oikawa Y, Haisa A, Suzuki S, Nakanishi S, Katsuki T, Shimada A (2022) Clinical Significance of Insulin Peptide–specific Interferon-γ–related Immune Responses in Ketosis-prone Type 2 Diabetes. The Journal of Clinical Endocrinology & Metabolism 107:e2124–e2132
  • Schmidtmann C, Segelke D, Bennewitz J, Tetens J, Thaller G (2023) Genetic analysis of production traits and body size measurements and their relationships with metabolic diseases in German Holstein cattle. Journal of Dairy Science 106:421–438. https://doi.org/10.3168/jds.2022-22363
  • Shpigel NY, Chen R, Avidar Y, Bogin E (1996) Use of corticosteroids alone or combined with glucose to treat ketosis in dairy cows. Journal of the American Veterinary Medical Association 208:1702–1704
  • Soares RAN, Vargas G, Duffield T, Schenkel F, Squires EJ (2021) Genome-wide association study and functional analyses for clinical and subclinical ketosis in Holstein cattle. Journal of Dairy Science 104:10076–10089. https://doi.org/10.3168/jds.2020-20101
  • Wang S, Soni KG, Semache M, Casavant S, Fortier M, Pan L, Mitchell GA (2008) Lipolysis and the integrated physiology of lipid energy metabolism. Molecular genetics and metabolism 95:117–126
  • Wathes DC, Fenwick M, Cheng Z, Bourne N, Llewellyn S, Morris DG, Kenny D, Murphy J, Fitzpatrick R (2007) Influence of negative energy balance on cyclicity and fertility in the high producing dairy cow. Theriogenology 68:S232–S241. https://doi.org/https://doi.org/10.1016/j.theriogenology.2007.04.006
  • Yameogo N, Ouedraogo GA, Kanyandekwe C, Sawadogo GJ (2008) Relationship between ketosis and dairy cows’ blood metabolites in intensive production farms of the periurban area of Dakar. Tropical Animal Health and Production 40:483–490. https://doi.org/10.1007/s11250-007-9124-z
  • Yan Z, Huang H, Freebern E, Santos DJA, Dai D, Si J, Ma C, Cao J (2020) Integrating RNA-Seq with GWAS reveals novel insights into the molecular mechanism underpinning ketosis in cattle. 1–12
  • Zarrin M, De Matteis L, Vernay MCMB, Wellnitz O, van Dorland HA, Bruckmaier RM (2013) Long-term elevation of β-hydroxybutyrate in dairy cows through infusion: Effects on feed intake, milk production, and metabolism. Journal of Dairy Science 96:2960–2972. https://doi.org/https://doi.org/10.3168/jds.2012-6224
  • Zdzisińska B, Filar J, Paduch R, Kaczor J, Lokaj I, Kandefer-Szerszeń M (2000) The influence of ketone bodies and glucose on interferon, tumor necrosis factor production and NO release in bovine aorta endothelial cells. Veterinary Immunology and Immunopathology 74:237–247
  • Zhou A, Qu J, Liu M, Tso P (2020) The role of interstitial matrix and the lymphatic system in gastrointestinal lipid and lipoprotein metabolism. Frontiers in Physiology 11:4

Gene Enrichment and Pathway Analysis for Ketosis Resistance in Dairy Cattle: A GWAS-Based Approach

Year 2024, Volume: 11 Issue: 4, 1014 - 1022, 12.10.2024
https://doi.org/10.30910/turkjans.1522944

Abstract

Ketosis in dairy cattle is a common metabolic disorder that arises during the transition period from late gestation to early lactation. It is primarily caused by an imbalance between energy intake and expenditure, leading to an excessive accumulation of ketone bodies. This condition can significantly affect cattle health and productivity. Recent advances in genomic research, especially genome-wide association studies (GWAS), offer an opportunity to explore the genetic factors that contribute to ketosis resistance.
The aim of this study is to comprehensively review and analyze existing GWAS data using gene enrichment analysis to identify potential functional candidate gene pathways associated with ketosis resistance in dairy cattle. In this study, data obtained from seven different studies were examined and 640 non-repetitive genes were obtained after filtering. Using Enrichr, an online tool for gene annotation, pathway analysis was performed with human homologs of the identified genes. Our findings highlight the acylglycerol homeostasis pathway, the regulation of triglyceride metabolism, and the role of chylomicrons in maintaining metabolic balance during ketosis. Additionally, immune response pathways were found to be linked to the genes associated with ketosis, offering insights into the intricate interplay between metabolic and immune pathways in ketosis.
This study emphasizes the importance of understanding genetic factors in developing breeding strategies aimed at enhancing metabolic health and productivity in dairy cattle. Future research should focus on validating these candidate genes and exploring their mechanistic roles to facilitate targeted interventions and improve resistance to ketosis in dairy herds.

References

  • Al Odaib A, Shneider BL, Bennett MJ, Pober BR, Reyes-Mugica M, Friedman AL, Suchy FJ, Rinaldo P (1998) A defect in the transport of long-chain fatty acids associated with acute liver failure. New England Journal of Medicine 339:1752–1757
  • Bergman EN (1971) Hyperketonemia-ketogenesis and ketone body metabolism. Journal of dairy science 54:936–948
  • Carrier J, Stewart S, Godden S, Fetrow J, Rapnicki P (2004) Evaluation and Use of Three Cowside Tests for Detection of Subclinical Ketosis in Early Postpartum Cows. Journal of Dairy Science 87:3725–3735. https://doi.org/10.3168/jds.S0022-0302(04)73511-0
  • David Baird G (1982) Primary Ketosis in the High-Producing Dairy Cow: Clinical and Subclinical Disorders, Treatment, Prevention, and Outlook. Journal of Dairy Science 65:1–10. https://doi.org/https://doi.org/10.3168/jds.S0022-0302(82)82146-2
  • Evangelista JE, Xie Z, Marino GB, Nguyen N, Clarke DJB, Ma’ayan A (2023) Enrichr-KG: bridging enrichment analysis across multiple libraries. Nucleic Acids Research 51:W168–W179. https://doi.org/10.1093/nar/gkad393
  • Faruk S Al, Park B, Ha S, Lee S, Mamuad LL, Cho Y (2020) Comparative study on different field tests of ketosis using blood , milk , and urine in dairy cattle. Veterinární Medicína 65:199–206. https://doi.org/10.17221/69/2019-VETMED
  • Freebern E, Santos DJA, Fang L, Jiang J, Parker Gaddis KL, Liu GE, Vanraden PM, Maltecca C, Cole JB, Ma L (2020) GWAS and fine-mapping of livability and six disease traits in Holstein cattle. BMC Genomics 21:1–11. https://doi.org/10.1186/s12864-020-6461-z
  • Gaddis KLP, Jr JHM, Clay JS, Wolfe CW (2018) Genome-wide association study for ketosis in US Jerseys using producer-recorded data. Journal of Dairy Science 101:413–424. https://doi.org/10.3168/jds.2017-13383
  • Giammanco A, Cefalù AB, Noto D, Averna MR (2015) The pathophysiology of intestinal lipoprotein production. Frontiers in physiology 6:61
  • Hasin Y, Seldin M, Lusis A (2017) Multi-omics approaches to disease. Genome Biology 18:83. https://doi.org/10.1186/s13059-017-1215-1
  • Houten SM, Wanders RJA (2010) A general introduction to the biochemistry of mitochondrial fatty acid β-oxidation. Journal of inherited metabolic disease 33:469–477
  • Huang H, Cao J, Hanif Q, Wang Y, Yu Y, Zhang S, Zhang Y (2019) Genome-wide association study identifies energy metabolism genes for resistance to ketosis in Chinese Holstein cattle. Animal Genetics 50:376–380. https://doi.org/10.1111/age.12802
  • Krebs H (1960) Biochemical aspects of ketosis. Içinde: Proceedings of the Royal Society of Medicine. SAGE Publications, ss 71–80
  • Kroezen V, Schenkel FS, Miglior F, Baes CF, Squires EJ (2018) Candidate gene association analyses for ketosis resistance in Holsteins. Journal of Dairy Science 101:5240–5249. https://doi.org/10.3168/jds.2017-13374
  • Leroy JLMR, Van Soom A, Opsomer G, Bols PEJ (2008) The consequences of metabolic changes in high-yielding dairy cows on oocyte and embryo quality*. Animal 2:1120–1127. https://doi.org/https://doi.org/10.1017/S1751731108002383
  • Littledike ET, Young JW, Beitz DC (1981) Common Metabolic Diseases of Cattle: Ketosis, Milk Fever, Grass Tetany, and Downer Cow Complex1. Journal of Dairy Science 64:1465–1482. https://doi.org/https://doi.org/10.3168/jds.S0022-0302(81)82715-4
  • McGarry JD, Foster DW (1972) Regulation of ketogenesis and clinical aspects of the ketotic state. Metabolism 21:471–489. https://doi.org/https://doi.org/10.1016/0026-0495(72)90059-5
  • McSherry BJ, Maplesden DC, Branion HD (1960) Ketosis in Cattle-a Review. The Canadian veterinary journal = La revue veterinaire canadienne 1:208–213
  • Nayeri S, Schenkel F, Fleming A, Kroezen V, Sargolzaei M, Baes C, Cánovas A, Squires J, Miglior F (2019) Genome-wide association analysis for β-hydroxybutyrate concentration in Milk in Holstein dairy cattle. BMC genetics 20:1–17
  • Nielsen NI, Ingvartsen KL (2004) Propylene glycol for dairy cows: A review of the metabolism of propylene glycol and its effects on physiological parameters, feed intake, milk production and risk of ketosis. Animal Feed Science and Technology 115:191–213
  • Oetzel GR, Mcguirk SM (2008) Evaluation of a Hand-Held Meter for Cowside Evaluation of Blood Beta- Hydroxybutyrate and Glucose Concentrations in Dairy Cows. 41:53706
  • Ofori EK (2023) Lipids and Lipoprotein Metabolism, Dyslipidemias, and Management. Içinde: Current Trends in the Diagnosis and Management of Metabolic Disorders. CRC Press, ss 150–170
  • Packard CJ, Boren J, Taskinen M-R (2020) Causes and consequences of hypertriglyceridemia. Frontiers in endocrinology 11:252
  • Pryce JE, Parker Gaddis KL, Koeck A, Bastin C, Abdelsayed M, Gengler N, Miglior F, Heringstad B, Egger-Danner C, Stock KF, Bradley AJ, Cole JB (2016) Invited review: Opportunities for genetic improvement of metabolic diseases. Journal of Dairy Science 99:6855–6873. https://doi.org/10.3168/jds.2016-10854
  • Sakai T, Hayakawa T, Hamakawa M, Ogura K, Kubo S (1993) Therapeutic Effects of Simultaneous Use of Glucose and Insulin in Ketotic Dairy Cows. Journal of Dairy Science 76:109–114. https://doi.org/https://doi.org/10.3168/jds.S0022-0302(93)77329-4
  • Satomura A, Oikawa Y, Haisa A, Suzuki S, Nakanishi S, Katsuki T, Shimada A (2022) Clinical Significance of Insulin Peptide–specific Interferon-γ–related Immune Responses in Ketosis-prone Type 2 Diabetes. The Journal of Clinical Endocrinology & Metabolism 107:e2124–e2132
  • Schmidtmann C, Segelke D, Bennewitz J, Tetens J, Thaller G (2023) Genetic analysis of production traits and body size measurements and their relationships with metabolic diseases in German Holstein cattle. Journal of Dairy Science 106:421–438. https://doi.org/10.3168/jds.2022-22363
  • Shpigel NY, Chen R, Avidar Y, Bogin E (1996) Use of corticosteroids alone or combined with glucose to treat ketosis in dairy cows. Journal of the American Veterinary Medical Association 208:1702–1704
  • Soares RAN, Vargas G, Duffield T, Schenkel F, Squires EJ (2021) Genome-wide association study and functional analyses for clinical and subclinical ketosis in Holstein cattle. Journal of Dairy Science 104:10076–10089. https://doi.org/10.3168/jds.2020-20101
  • Wang S, Soni KG, Semache M, Casavant S, Fortier M, Pan L, Mitchell GA (2008) Lipolysis and the integrated physiology of lipid energy metabolism. Molecular genetics and metabolism 95:117–126
  • Wathes DC, Fenwick M, Cheng Z, Bourne N, Llewellyn S, Morris DG, Kenny D, Murphy J, Fitzpatrick R (2007) Influence of negative energy balance on cyclicity and fertility in the high producing dairy cow. Theriogenology 68:S232–S241. https://doi.org/https://doi.org/10.1016/j.theriogenology.2007.04.006
  • Yameogo N, Ouedraogo GA, Kanyandekwe C, Sawadogo GJ (2008) Relationship between ketosis and dairy cows’ blood metabolites in intensive production farms of the periurban area of Dakar. Tropical Animal Health and Production 40:483–490. https://doi.org/10.1007/s11250-007-9124-z
  • Yan Z, Huang H, Freebern E, Santos DJA, Dai D, Si J, Ma C, Cao J (2020) Integrating RNA-Seq with GWAS reveals novel insights into the molecular mechanism underpinning ketosis in cattle. 1–12
  • Zarrin M, De Matteis L, Vernay MCMB, Wellnitz O, van Dorland HA, Bruckmaier RM (2013) Long-term elevation of β-hydroxybutyrate in dairy cows through infusion: Effects on feed intake, milk production, and metabolism. Journal of Dairy Science 96:2960–2972. https://doi.org/https://doi.org/10.3168/jds.2012-6224
  • Zdzisińska B, Filar J, Paduch R, Kaczor J, Lokaj I, Kandefer-Szerszeń M (2000) The influence of ketone bodies and glucose on interferon, tumor necrosis factor production and NO release in bovine aorta endothelial cells. Veterinary Immunology and Immunopathology 74:237–247
  • Zhou A, Qu J, Liu M, Tso P (2020) The role of interstitial matrix and the lymphatic system in gastrointestinal lipid and lipoprotein metabolism. Frontiers in Physiology 11:4
There are 36 citations in total.

Details

Primary Language English
Subjects Stock Farming and Treatment, Animal Science, Genetics and Biostatistics
Journal Section Research Article
Authors

Veysel Bay 0000-0002-9339-4840

Early Pub Date October 12, 2024
Publication Date October 12, 2024
Submission Date July 27, 2024
Acceptance Date August 13, 2024
Published in Issue Year 2024 Volume: 11 Issue: 4

Cite

APA Bay, V. (2024). Gene Enrichment and Pathway Analysis for Ketosis Resistance in Dairy Cattle: A GWAS-Based Approach. Türk Tarım Ve Doğa Bilimleri Dergisi, 11(4), 1014-1022. https://doi.org/10.30910/turkjans.1522944