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An Algorithm for Finding Optimal Descent Trees in Genealogies Conditional on the Observed Data.

机译:一种以观测数据为条件的家谱中最佳后代树的算法。

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摘要

There are many diseases caused by genes such as cystic fibrosis, hereditary spherocytosis and duchenne muscular dystrophy. Identifying the actual disease--causing genes is important since it may help prevent or avoid genetic disorder. Finding out which genes contribute to diseases is also helpful for understanding why some individuals are more inclined to have physical diseases than others. To do this, we should determine regions of chromosomes that are likely to contain the particular genes responsible for a given human disease. Genetic linkage analysis is developed as a statistical method that allows us to determine these regions of chromosomes.;In chapter 1, we first provide background of finding optimal subpedigrees in a large original pedigree problem, in particular, one method to find such subpedigrees that uses graph theory techniques. Then, we introduce some terminologies in graph theory related to the Steiner tree problem. At the end of this chapter, some basic ideas about statistical genetics are provided.;Chapter 2 concentrates on the description of constructing subpedigrees in a large pedigree based on the Steiner tree problem in graph theory. Two pieces of software, PedHunter and Miniped, that use the Steiner tree algorithm in constructing optimal subpedigrees are introduced. The study in this chapter also enables us to consider the most likely descent trees conditional on the observed data.;Chapter 3 is devoted to the study of algorithms for finding the most likely descent trees. We first present an algorithm to find the probability of every edge in all possible descent trees, and then reformulate this problem into a directed Steiner tree problem in graph theory. Furthermore, we provide an approximation algorithm to solve this directed Steiner tree problem.;Geneticists use pedigrees because they offer many advantages for genetic mapping regardless of the incidence of the genetic disease. One of this advantages is that study of pedigrees is quite powerful if the disease is rare, nevertheless there are many other aspects, like genetic homogeneity, the patterns of transmission, etc. These advantages make the study of pedigrees attractive. However, utilizing such pedigrees in genetic analysis is a computationally challenging task. Time complexity of some algorithms for genetic analysis is exponential in the size of the pedigree. Therefore, it is desirable to find a potentialy optimal subpedigree that connects the individuals with the disorder. The aim of this thesis is to study the methods of finding optimal subpedigrees conditional on the observed data in a large pedigree.;The final chapter summarizes the results in this thesis and points out some problems for future study.
机译:有许多疾病是由基因引起的,例如囊性纤维化,遗传性球囊病和杜氏肌营养不良症。识别导致疾病的实际基因很重要,因为它可以帮助预防或避免遗传疾病。找出导致疾病的基因也有助于理解为什么某些人比其他人更容易患上身体疾病。为此,我们应该确定可能包含导致特定人类疾病的特定基因的染色体区域。遗传连锁分析是一种统计方法,可以让我们确定染色体的这些区域。在第一章中,我们首先提供了在一个大型原始谱系问题中寻找最佳子谱系的背景,特别是一种使用以下方法找到此类子谱系的方法图论技术。然后,我们介绍图论中与Steiner树问题有关的一些术语。在本章的最后,提供了有关统计遗传学的一些基本思想。第二章着重于基于图论中的斯坦纳树问题,对在大谱系中构建子谱系的描述。介绍了使用Steiner树算法构建最佳子谱系的两个软件PedHunter和Miniped。本章的研究还使我们能够根据观察到的数据来考虑最可能的后裔树。第三章专门研究寻找最可能的后裔树的算法。我们首先提出一种算法,以找到所有可能下降树中每个边的概率,然后在图论中将此问题重新表述为有向Steiner树问题。此外,我们提供了一种近似算法来解决该定向Steiner树问题。遗传学家使用谱系,因为它们为遗传作图提供了许多优势,而与遗传疾病的发生率无关。这种优势之一是,如果这种疾病很少见,那么谱系的研究就会非常有力,尽管如此,它还有许多其他方面,例如遗传同质性,传播方式等。这些优势使谱系的研究具有吸引力。然而,在遗传分析中利用这种谱系是一项计算上的挑战性任务。某些遗传分析算法的时间复杂度在谱系中呈指数级增长。因此,期望找到将个体与疾病联系起来的潜在的最佳子谱系。本文的目的是研究在大的谱系中以观测数据为条件寻找最佳子谱系的方法。最后一章总结了本文的研究成果,并指出了一些需要进一步研究的问题。

著录项

  • 作者

    Li, Qiong.;

  • 作者单位

    Memorial University of Newfoundland (Canada).;

  • 授予单位 Memorial University of Newfoundland (Canada).;
  • 学科 Statistics.
  • 学位 M.Sc.
  • 年度 2010
  • 页码 57 p.
  • 总页数 57
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 普通生物学;
  • 关键词

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