فراتحلیل مطالعات پویش ژنومی برای صفت نمره سلول‌های بدنی در گاوهای شیری

نوع مقاله : مقاله پژوهشی

نویسندگان

1 دانشجوی دکتری، گروه علوم دامی، دانشکده کشاورزی، دانشگاه فردوسی مشهد

2 استاد ، گروه علوم دامی، دانشکده کشاورزی، دانشگاه فردوسی مشهد

3 استادیار ، گروه علوم دامی، دانشکده کشاورزی، دانشگاه فردوسی مشهد

چکیده

سابقه و هدف: ورم‌پستان یک بیماری التهابی در گاوهای شیری است که در پاسخ به قرار گرفتن در محیطی با عوامل عفونی رُخ می‌دهد. این بیماری التهابی، خسارات اقتصادی فراوانی را بر صنعت گاو شیری وارد می‌کند. در دهه‌های اخیر، از امتیازدهی سلول‌های بدنی به عنوان روشی غیرمستقیم برای کنترل ورم‌پستان استفاده شده است. مقاومت در برابر بیماری‌های عفونت‌زا به صورت توانایی پاسخ ایمنی حیوان در جلوگیری از تکثیر عوامل بیماری‌زا پس از ایجاد عفونت تعریف می‌شود. مطالعات نشان داده‌اند که حیوانات، توانایی ژنتیکی متفاوتی برای ایجاد پاسخ ایمنی در برابر بیماری ورم‌پستان دارند. مقاومت ژنتیکی به ورم‌پستان شامل سازوکارهای بیولوژیکی به هم پیوسته‌ای است که در نتیجه تفاوت‌های موجود در پاسخ به ورم‌پستان ایجاد می‌شود و سطوح مختلف پاسخ ایمنی را فعّال و تنظیم می‌کند. درک بهتر سیستم ایمنی بدن و مسیرهای متابولیکی درگیر در پاسخ به عوامل مختلف بیماری‌زا ممکن است به عنوان روشی مکمل برای کنترل بیماری استفاده شود. تحقیقات متعدّدی سازوکارهای ژنتیکی مؤثّر بر امتیازدهی سلول‌های سوماتیک را در گاوهای شیری مورد بررسی و ارزیابی قرار داده‌اند. بسیاری از ژن‌های کاندیدای مؤثّر بر امتیازدهی سلول‌های سوماتیک معرفی شده است، امّا هنوز روابط پیچیده‌ی بین ژن‌ها و مسیرهای مؤثّر بر آن به طور کامل مشخّص نشده است. هدف اصلی این تحقیق، یکپارچه‌سازی و فراتحلیل نتایج حاصل از تحقیقات اخیر در زمینه مطالعات پویش ژنومی به منظور دست‌یابی به مجموعه‌ای از ژن-های مهم و مسیرهای غنی‌شده در ارتباط با بیماری ورم‌پستان می‌باشد.
مواد و روش‌ها: جستجو برای مجموعه مطالعات پویش ژنومی در گوگل اسکولار با استفاده از کلید واژه‌های گاوهای شیری، مطالعات پویش ژنومی و امتیازدهی سلول‌های بدنی انجام شد. مجموعه ژن‌های حاصل در جمعیّت‌های مختلفی از نژادهای گاوهای شیری (نژاد هلشتاین و فریزین و گاوهای قرمز رنگ) در 11 مطالعه مستقل از سال 2011 تا 2019 در دسترس بود. تعداد 218 ژن از مطالعات قبلی مطالعات پویش ژنومی، مورد بررسی قرار گرفت. با استفاده از نمودار ون، تعداد ژن‌های مشترک در گاوهای شیری مورد بررسی قرار گرفت. سپس، تمامی ژن‌های قابل دسترس با استفاده از روش فراتحلیل با هم ترکیب و ارزیابی شدند. برای تجزیه و تحلیل هستی‌شناسی ژن‌ها و مسیرهای KEGG از پلاگین ClueGO v2.5.4 و برای تجسّم ژن‌ها و تعاملات پروتئین - پروتئین از پلاگین CluePedia v1.5.4 در نرم‌افزار Cytoscape v3.7.2 استفاده شد.
یافته‌ها: نتایج این مطالعه نشان داد که ژن‌های U6، DCK و NPFFR2 به عنوان اصلی‌ترین ژن‌های کاندیدا، نقش مهمی در مقابله با عفونت و عوامل بیماری‌زا در بروز بیماری ورم‌پستان دارند. فرآیندهای بیولوژیکی، اجزای سلولی، عملکرد مولکولی و مسیرهای مرتبط مورد شناسایی قرار گرفت. مهمترین مسیرهای فرآیند بیولوژیکی، اجزای سلولی و عملکرد مولکولی به ترتیب رشد سلولی مزانشیمی (4e-92/3P=)، غشای پلاسمایی آپیکال (3e-83/2P=) و املاح: فعالیّت همزمان کاتیونی (4e-71/3P=) بودند.
نتیجه‌گیری: در مجموع، نتایج این پژوهش نشان داد که فراتحلیل مبتنی بر ترکیب مطالعات مستقل، مهمترین ژن‌های کاندیدا و مسیرهای مقابله با ورم‌پستان را آشکار می‌نماید. این اطلاعات پایه‌های محکمی را برای توسعه درمان‌های جدید ورم‌پستان فراهم می-کند. بنابراین، شناسایی ژن‌های مهم و غنی‌سازی عبارات هستی‌شناسی ژن‌ها (با توان و صحّت بالا) می‌تواند نقش مؤثّری در ارزیابی ژنومی و طراحی برنامه‌های اصلاح‌نژادی با هدف کنترل ورم‌پستان در گاوهای شیری داشته باشد

کلیدواژه‌ها


عنوان مقاله [English]

Meta-analysis of genome-wide association studies for somatic cells score trait in dairy cows

نویسندگان [English]

  • Somaieh Bakhshalizadeh 1
  • Saeed Zerehdaran 2
  • Ali Javadmanesh 3
1 Department of Animal Science, Faculty of Agriculture, Ferdowsi University of Mashhad, Mashhad, Iran
2 Animal Science department, Faculty of Agriculture, Ferdowsi University of Mashhad
3 Department of Animal Science, Faculty of Agriculture, Ferdowsi University of Mashhad, Mashhad, Iran
چکیده [English]

Background and objectives: Mastitis is an inflammatory disease in dairy cows that occurs in response to infectious factors. This inflammatory disease have a high negative economic impact on dairy industry. In recent decades, somatic cell score has been used as an indirect method to control mastitis. Resistance to infection disease may be defined as the ability of an animal to have an immune response to prevent the spread of pathogens after infection. Previous studies showed that animals differ in their genetic ability for immune competence. Genetic resistance to mastitis involves interconnected biological mechanisms that result from differences in the response to mastitis that activate and regulate different levels of the immune response. A better understanding of the immune system and the metabolic pathways involved in responding to various pathogens may be used as a complementary approach to control of the disease. Several studies have been evaluated genetic mechanisms affecting somatic cells score in dairy cows. Many candidate genes affecting somatic cells score has been introduced. But the complex relationships between genes and pathways that affect them have not been fully identified yet. The main purpose of this study is to integrate the results of recent genome-wide association studies on somatic cells score using meta-analysis to obtain a set of important genes and pathways.
Materials and methods: In this study, a search for the genome-wide association studies dataset in Google Scholar was performed using the keywords Dairy cows, Genome wide association studies, and Somatic cells score. Gene sets were available in different populations of dairy cow breeds (Holstein and Friesian breeds and red cows) in 11 independent studies from 2011 to 2019. 218 candidate genes for somatic cells score were found from genome-wide association studies. The number of common genes in dairy cows was examined using Venn diagram. Then, all available genes were combined and evaluated using meta-analysis. The ClueGO v2.5.4 plugin were used to conduct gene ontology analysis and KEGG pathways. The CluePedia v1.5.4 plugin in Cytoscape v3.7.2 were used to visualize genes and protein-protein interactions.
Results: The results showed that U6, DCK, and NPFFR2 genes as the key candidate genes have an important role in combating infection and pathogens in the development of mastitis. Some biological processes, cellular components, molecular functions, and related pathways were identified. The most important biological process, cellular components and molecular function pathways were mesenchymal cell development (P=3.92e-04), apical plasma membrane (P=2.83e-03), and solute: cation symporter activity (P=3.71e-04), respectively.
Conclusion: Generally, the results of this study showed that meta-analysis based on a large number of original data revealed the most important candidate genes involved in the fight against mastitis pathways, this information provides a solid foundation for the development of new treatments for mastitis. Therefore, identification of important genes and gene ontology term enrichment (with high power and accuracy) can play an effective role in genomic evaluation and design of breeding programs aimed at controlling mastitis in dairy cows.

کلیدواژه‌ها [English]

  • Somatic cells score
  • Meta-analysis
  • Dairy cows
  • Genome wide association
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