پویش پیوستگی ژنومی جهت شناسایی ژن‌های کاندیدا و مسیرهای زیستی مرتبط با مقاومت به بیماری سل گاوی بر پایه آنالیز غنی‌سازی مجموعه‌های ژنی

نوع مقاله : مقاله پژوهشی

نویسندگان

گروه علوم دامی، دانشکده کشاورزی و محیط زیست، دانشگاه اراک، اراک، ایران

چکیده

شناسایی مسیرهای زیستی و ژن­های مرتبط با بیماری­ها یکی از مهم‌ترین اهداف برنامه­های اصلاح­نژادی در گاو شیری است. پژوهش حاضر به منظور مطالعه پویش پیوستگی ژنومی جهت شناسایی ژن­های کاندیدا و مسیرهای زیستی مرتبط با مقاومت به بیماری سل گاوی بر پایه آنالیز غنی­سازی مجموعه­های ژنی انجام شد. به این منظور از اطلاعات مجموع، 1355 رأس گاو هلشتاین (685 حیوان بیمار و 670 حیوان شاهد) از 178 گله استفاده شد که پس از انجام مراحل مختلف کنترل کیفیت، اطلاعات ژنوتیپی 592 نمونه گاو بیمار و 559 نمونه گاو سالم در آنالیزهای نهایی استفاده شدند. تعیین ژنوتیپ این حیوانات با استفاده از تراشه­های ژنومیIllumina BovineHD 700k BeadChip برای 727252 جایگاه نشانگری SNP انجام شد. پویش پیوستگی ژنومی (GWAS) با استفاده از مدل­های خطی مختلط لجستیک مورد بررسی قرار گرفت و مناطقی از ژنوم که در سطح 05/0 با بیماری سل گاوی در ارتباط بودند به منظور شناسایی ژن­های کاندیدا و مسیرهای زیستی مرتبط با مقاومت به بیماری سل گاوی بر پایه آنالیز غنی­سازی مجموعه­های ژنی استفاده شد. نتایج این تحقیق در نهایت منجر به شناسایی مسیرهایی، از قبیل مسیرهای تنظیم مثبت فرآیند آپوپتوز، سازماندهی اتصالات سلولی، تنظیم منفی تولید سیتوکین و تنظیم پاسخ دفاعی شد که به طور معنی­داری با بیماری سل گاوی در ارتباط بودند. بررسی این مسیرها نشان داد که اغلب آنها با سیستم ایمنی، کنترل استرس و مقاومت در برابر بیماری­ها در ارتباط هستند. همچنین ارزیابی عملکرد ژن­های موجود در این مسیرها نشان داد که ارتباط مستقیم برخی از این ژن­ها مانند SLC11A1، SLC2A2 و CD80 و غیر مستقیم ژن­هایی مانند BCL6، HSPD1، KCNMA1، SPP1، CD24، MYO1B، CCL20، و LCP2 با مقاومت به بیماری­ها و سل گاوی در تحقیقات گذشته نیز تأیید شده است. در مجموع، با توجه به اهمیت شناسایی جایگاه­های ژنی تأثیرگذار بر سل گاوی از دیدگاه علمی و اقتصادی، نتایج این تحقیق نشان می­دهد مقاومت به بیماری سل گاوی با مسیرهای زیستی و ژن­های کاندیدای مرتبط با سیستم عصبی، ایمنی ذاتی، پاسخ به التهابات، تنظیم پاسخ ایمنی، اتصالات سلولی و هموستازی گلوکز ارتباط نزدیکی دارد.

کلیدواژه‌ها

موضوعات

عنوان مقاله [English]

Genome-wide association study to identify genes and biological pathways related to resistance to bovine tuberculosis based on gene set enrichment analysis

نویسندگان [English]

  • Mohsen Abdollahi
  • Mohammad Hossein Moradi
  • Amir Hossein Khaltabadi Farahani
  • Hossein Mohammadi
Department of Animal Science, Faculty of Agriculture and Natural Resources, Arak University, Arak, Iran.
چکیده [English]

Identifying biological pathways and genes associated with diseases is one of the most important goals of breeding programs in dairy cattle. The aim of the present study was to conduct a genome-wide association study (GWAS) to identify the genes and biological pathways related to resistance to bovine tuberculosis based on gene set enrichment analysis. In total, the information of 1355 cows (consisting 685 cases and 670 controls) from 178 herds were used, of which 592 cases and 559 controls (healthy cows) were passed different quality control steps. These animals were genotyped by using Illumina BovineHD 700k BeadChip for 727252 SNP markers. Genome-wide association study (GWAS) was investigated using mixed linear logistic models, and regions of the genome that were associated with bovine tuberculosis at the 0.05 level were used for identifying the candida genes and biological pathways associated with bovine tuberculosis based on gene set enrichment analysis. The results of this study finally led to the identification of the pathways such as positive regulation of apoptotic process, cell junction organization, negative regulation of cytokine production and regulation of defense response that were significantly associated with bovine tuberculosis. Further investigation of these pathways showed that most of them are related to the immune system, stress and disease resistance. Also, study of function of the genes that were located in these pathways revealed that the direct association of some of these genes, such as SLC11A1, SLC2A2, and CD80, and the indirect association of genes such as BCL6, HSPD1, KCNMA1, SPP1, CD24, MYO1B, CCL20, and LCP2 with disease resistance and bovine tuberculosis has also been confirmed in previous studies. In general, due to the importance of identifying the genes affecting bovine tuberculosis from a scientific and economic point of view, the results of this study show that resistance to bovine tuberculosis is closely related to biological pathways and candidate genes associated with nervous system, innate immunity, inflammatory response, immune response regulation, cell junctions, and glucose homeostasis.

کلیدواژه‌ها [English]

  • Genome-wide association study (GWAS)
  • Gene set enrichment
  • Bovine Tuberculosis
  • Holstein dairy cattle

Extended Abstract

Introduction

The identification of genes and pathways that influence economically important traits is one of the main goals in the breeding of dairy cattle. Bovine tuberculosis (bTB), poses significant economic challenges to the livestock industry due to its detrimental effects on animal health and productivity. Understanding the genetic basis of resistance to this disease can facilitate better management practices and breeding strategies aimed at enhancing disease resistance in cattle populations. The objective of this study was to conduct a genome-wide association study (GWAS) to identify genes and biological pathways associated with resistance to bovine tuberculosis through gene set enrichment analysis.

 

Methods and Materials

In this study, data were collected from a total of 1355 cows, including 685 cases (infected with bTB) and 670 controls (healthy animals), derived from 178 herds. Following various quality control measures, 592 cases and 559 healthy controls retained for further analysis. The genotyping was performed using the Illumina BovineHD 700k BeadChip, which provides comprehensive coverage across the bovine genome with a total of 727252 SNP markers. To investigate associations between SNPs and bovine tuberculosis resistance, mixed linear logistic models were employed. Subsequently, gene set enrichment analysis was conducted on the regions that were associated with bovine tuberculosis at the 0.05 level, to elucidate their biological implications regarding pathways related to immune response, stress regulation, and disease resistance.

 

Results

 Our findings revealed several significant genomic regions linked with bovine tuberculosis susceptibility at p < 0.05 level through GWAS analyses. Gene set enrichment analysis led to the identification of the pathways that were significantly associated with bovine tuberculosis. Further investigation of these pathways showed that most of them are related to the immune system, stress and disease resistance. Also, study of function of the genes that were located in these pathways revealed that some of these genes such as HSPD1, BCL6, KCNMA1, SPP1, CD24, CD80, MYO1B, CCL20, SLC11A1, LCP2 and SLC2A2, have also been confirmed to be directly or indirectly associated with disease resistance and bovine tuberculosis in previous studies.

 

Conclusion

In general, the results of this study elucidate critical biological pathways involved in the mechanisms of disease resistance, specifically in relation to bovine tuberculosis. These findings not only have the potential to improve animal health but also to enhance overall productivity within dairy farms. Furthermore, this research contributes significantly to identifying genomic regions associated with key phenotypic traits, particularly those related to disease resistance, immunity, and adaptability. Given the increasing economic importance of these traits amid observable climatic changes in recent years across various countries, our findings could help future breeding strategies aimed at developing more resilient livestock populations.

Author Contributions

Conceptualization, M.A, and M.H.M; methodology, M.H.M, and H.M; software, M.H.M, and A.H.K.F; validation, M.H.M, and M.A; formal analysis, M.A; investigation, M.H.M, H.M; resources, M.H.M; data curation, M.H.M, A.H.K.F; writing-original draft preparation, M.A; writing-review and editing, M.H.M, A.H.K.F, H.M; visualization, M.H.M; supervision, M.H.M; project administration, M.H.M, H.M; funding acquisition, M.H.M. All authors have read and agreed to the published version of the manuscript.”

Data Availability Statement

This article contains all the data that were created or evaluated during the research.

Acknowledgements

We sincerely thank all authors who made their data available for the present research. The authors also acknowledge the supports and contributions of Arak University for the approval and support of this research.

Ethical considerations

The study was approved by the Ethics Committee of the Agricultural Science and Natural Resources University of Arak, Iran (Code: 1403.0731). The authors avoided data fabrication, falsification, plagiarism, and misconduct.

Conflict of interest

The author declares no conflict of interest.

مراجع

منابع

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علوم دامی ایران
دوره 56، شماره 3
مهر 1404
صفحه 707-722

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سابقه مقاله

  • تاریخ دریافت: 01 دی 1403
  • تاریخ بازنگری: 11 بهمن 1403
  • تاریخ پذیرش: 28 بهمن 1403

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