Mathematical Sciences: Problems in Population Genetics

理论模型和DNA序列分析将用于研究基因转化和遗传学中的其他问题。将研究一系列特殊的统计测试，这些测试可以检测基因转换的特定实例以及基因转换的神秘模式。其中一个目标是开发参数模型，允许根据DNA序列数据联合估计基因转化率和点突变率。第二个主要目标将是应用这些技术来研究Alu重复序列家族的基因转换，该家族在人类基因组中有大约50万个重复序列，约占人类DNA总量的5%。还将研究Alu重复序列的亚家族结构和关系，这既是为了它们本身，也是为了研究家族异质性可能在多大程度上影响基因转换的统计测试。遗传物质的自发突变是进化和遗传病的主要贡献者。在许多特殊情况下，这种突变不是纯粹随机的，而是附近类似遗传物质的转换或复制过程的结果。该提案的第一部分将开发测试，以检测可能看起来纯粹随机的隐秘的基因转换模式，并估计这两个突变过程在特定遗传位点的相对重要性。一种显著的基因转换模式可能暗示着附近有一个相似的遗传位点。ALU序列不仅因为它们可以揭示遗传物质的进化和结构而令人感兴趣，还被用来作为人类DNA片段的标签，这些片段已经被克隆到细菌质粒或酵母染色体中。如果附近的Alu序列在特定情况下表现出基因转换的模式，这将有助于在构建人类基因组图谱时拼凑这些克隆。

Theoretical models and DNA sequence analysis will be used to study gene conversion and other problems in genetics. A particular family of statistical tests that can detect specific instances of gene conversion as well as cryptic patterns of gene conversion will be studied. One aim will be to develop parametric models that would allow gene conversion and point mutation rates to be jointly estimated from DNA sequence data. A second major goal will be to apply these techniques to study gene conversion in the Alu family of repeated sequences, which has about 500,000 repeats in the human genome and constitutes about 5 per cent of total human DNA. The subfamily structure and relationships of the Alu repeats will also be studied, both for their own sake and for the extent to which family heterogeneity may affect statistical tests for gene conversion. The spontaneous mutation of genetic material is a major contributor both to evolution and to genetic disease. In many particular cases this mutation, rather than being purely random, has been shown to be the result of a conversion or copying process from nearby similar genetic material. The first part of the proposal will develop tests for detecting a cryptic pattern of gene conversion that may appear purely random, and to estimate the relative importance of the two mutational processes at a particular genetic loci. A significant pattern of gene conversion may imply a similar nearby genetic locus. Alu sequences are not only interesting for what they can tell about the evolution and structure of genetic material, they also have been used as tags of pieces of human DNA that have been cloned into bacterial plasmids or yeast chromosomes. If nearby Alu sequences show a pattern of gene conversion under certain circumstances, this can help to piece together these clones in the construction of the human genomic map.