برآورد اثر لایه بندی جمعیتی در گله های خویشاوند و آمیخته گاوهای شیری به روش مطالعات ارتباطی کل ژنومی با شبیه سازی

نوع مقاله : علمی پژوهشی- ژنتیک و اصلاح دام و طیور

نویسندگان

1 دانشگاه فردوسی مشهد

2 فردوسی مشهد

چکیده

لایه بندی جمعیتی5 یکی از مسائلی است که می تواند در مطالعات ارتباطی ژنومی باعث بروز خطا شود. در تحقیق حاضر از شیوه مطالعه ارتباطی ژنومی (طرح Case-Control) برای شناسایی اثر لایه بندی جمعیتی استفاده شد. جامعه آماری و ژنوم 10000 گاو در طی 100 نسل با روش تعادل رانش – جهش ژنتیکی شبیه سازی و سپس با استفاده از جامعه مذکور، 800 گاو آمیخته و خالص با 50000 SNP تعیین ژنوتیپ شده در طول 30 جفت کروموزوم، ایجاد شدند. نتایج نشان داد که هر چه نسبت Case/Control در بین جوامع خویشاوند از عدد یک بیشتر منحرف شود، شاخص آماری لامبدا که نشان دهنده اثر لایه بندی جمعیتی است، افزایش خواهد یافت. به طوری که شاخص لامبدا در مدل ژنتیکی افزایشی با نسبت های 1، 77/0 و 33/0 به ترتیب 42/0 ، 31/11 و 77/97 و در مدل ژنتیکی عدم غلبه، به ترتیب 47/0 ، 21/8 و 40/57 برآورد گردید. اثر لایه بندی جمعیتی در بین گروههای مختلف جامعه گاوهای آمیخته وجود نداشت و شاخص لامبدا در مدلهای ژنتیکی عدم غلبه، غلبه کامل، مغلوبیت، افزایشی و فوق غلبه به ترتیب 55/0 ، 66/0 ، 89/0 ، 76/0 و 41/0 برآورد شد. نتایج تحقیق حاضر نشان داد که برای کنترل اثر لایه بندی جمعیتی در مطالعات ارتباطی ژنومی، گروههای case-control نبایستی از جوامعی مختلف با اجداد و درجه خویشاوندی متفاوت انتخاب شوند، مگر با نسبتهای کاملا یکنواخت در دو جامعه. همچنین، پیشنهاد می گردد از گاوهای آمیخته به دلیل عدم وجود عامل ساختار ژنتیکی جمعیتی استفاده گردد.

کلیدواژه‌ها


عنوان مقاله [English]

Estimation of population stratification in crossbred and inbred dairy cattle using genome wide association by simulation

نویسندگان [English]

  • Morteza Bitaraf Sani 1
  • Mohammadreza Nassiri 2
  • Ali Asghar Aslaminejad 2
  • Mohammad Mahdi Shariati 2
1 Ferdowsi University of Mashhad
2 Ferdowsi University of Mashhad
چکیده [English]

Introduction: Domestic animals are invaluable resources to study the molecular architecture of complex traits. Although the mapping of quantitative trait loci (QTL) underlying economically important traits in domestic animals has achieved remarkable results in recent decades, not all of the genetic variation in the complex traits has been captured due to the low density of markers used in QTL mapping studies. The genome wide association study (GWAS) utilizing high-density single-nucleotide polymorphism (SNP), provides a new way to tackle this issue. Genetic association tests identify differences in allele frequency between cases and controls. Population stratification can be a problem in association studies, such as case-control studies, where the association found could be due to the underlying structure of the population.

Material and Methods: In current research, Genome wide association technique (Case-control design) was used to evaluate population stratification. Historical population and genome of 10000 cattle were simulated along 100 generations by Mutation-Drift Equilibrium (MDA) technique. By using historical population, 800 inbred and cross bred cattle with ~50000 SNPs on 30 chromosomes were simulated. Genomic control was performed to survey markers with a low prior probability of association with trait (“null markers”) and to estimate population stratification by Q-Q plot and lambda statistics.

Results and discussion: Deviation of cases/controls ratios between inbred subpopulations causes increasing lambda and population stratification; as lambda was estimated 0.42, 11.31 and 97.77 in additive genetic model with case/control ratios 1.00, 0.77 and 0.33, respectively and 0.47, 8.21 and 57.40 in co-dominant genetic model. Therefore, the more disparate composition cases/controls the more population stratification. When cases and controls were drawn from different randomly mating breeding populations, allele frequencies were different, but these differences may not be related to disease status or complex trait. This means that the assumption of independence of observations is violated. Often this will lead to an overestimation of the significance of an association but it depends on the way the sample is chosen. Population stratification was surveyed between two random groups of crossbred population (400 cases, 400 controls). There was no population stratification among subpopulations of crossbreds in current research; as lambda was estimated 0.55, 0.66, 0.89, 0.76 and 0.41 in co dominant, dominant, recessive, over dominant, additive genetic models, respectively.

Conclusion: The main GWAS problem in inbred cattle is population stratification. When cases and controls are drawn from different inbreeding populations, Population Stratification occurs. Lambda and PS is related to Cases/controls ratio among inbred lines, as more deviation ratio of one, more population stratification. It is suggested to control population stratification inbred cattle should not be used unless exactly equal ratio of cases/controls between inbred subpopulations can be achieved and it is better to use of crossbred cattle for genome wide association studies.

کلیدواژه‌ها [English]

  • Association Studies
  • Population Stratification
  • SNPs
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