Mosaic Haplotype Reference Panels for Minority Populations

少数民族群体的镶嵌单倍型参考面板

• 批准号: 9209739
• 负责人: LI MA
• 金额: $ 13.28万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9209739
• 关键词: Admixture; African; African American; Algorithms; Alleles; Bioinformatics; Cardiology; Cardiovascular system; Chromosomes; Code; Computer software; Computers; DNA; DNA Sequence; Data; Data Set; Databases; Diploidy; Ethnic Origin; European; Faculty; Fathers; Frequencies; Funding; Genetic; Genetic study; Genome; Genomic Segment; Genomics; Genotype; Goals; Haplotypes; Healthcare; Human; Income; Individual; Inherited; Internet; Jackson Heart Study; Java; Latino; Libraries; Medical Genetics; Mentors; Minority; Molecular Conformation; Mosaicism; Mothers; Mutation; Native Americans; Organism; Paper; Patients; Pharmacogenetics; Phase; Play; Population; Population Genetics; Population Heterogeneity; Population Study; Postdoctoral Fellow; Principal Investigator; Publications; Publishing; Pythons; Recipe; Records; Research; Role; Series; Somatic Cell; Statistical Algorithm; Statistical Computing; Statistical Models; Students; Technology; Training; Underrepresented Populations; Variant; base; career development; cohort; cost effective; epidemiology study; epigenome; experience; gene function; genetic information; genetic linkage analysis; genetic variant; genome wide association study; genomic data; health disparity; improved; men who have sex with men; novel; personalized strategies; precision medicine; student training; study population; whole genome

We aim to establish the haplotype reference panels for haplotype phasing in the US minority populations. Haplotype refers to a group of alleles inherited on a single chromosome; it describes the cis-conformation among alleles at different polymorphic loci and is thus essential for deciphering the synergistic cis-interactions among multiple variants. Haplotypes may play crucial roles in diverse contexts, including linkage analysis, association studies, population genetics, medical genetics and pharmacogenetics. As humans are diploid organisms, genetic information will be incomplete without the haplotypes ultimately. Recently a large reference panel has been established for European-derived populations (HRC, The Haplotype Reference Consortium), and the first release consists of 64,976 haplotypes from 20 large cohorts. However, there is a void of haplotype reference panel for the minority populations. First, minority populations are underrepresented in genome studies and thus the haplotypes are not available for many African Subpopulations. Second, both African-Americans and Latinos are heavily admixed populations, which have shaped their genomes into mosaic genomes. In these mosaic genomes, different genomic regions within the same individual were inherited from ancestors of different ethnic backgrounds, so any single-ethnicity reference panel cannot cover well the ancestral origins for an admixed individual for haplotype phasing. Third, due to dramatic variations from individuals to individuals on the admixture recipe and ratio, the phasing algorithms based on haplotype frequencies that have been used on homogeneous populations may not work well on heterogeneous populations such as African-Americans and Latinos. In this proposal, we will explore potential solutions for these challenges. Specifically, we will strategically utilize the large volume of existing unphased genotype datasets and convert them into haplotype references for minority populations; we will implement this reference panel and a haplotype phasing software into a web server, and incorporate a component of local ancestry determination with the aMAP software into the application package. The goal is to fill this void by solving this haplotype reference issue in minority populations.

我们的目标是建立用于美国少数民族人口单倍型定相的单倍型参考组。 单倍型是指在单条染色体上遗传的一组等位基因；它描述了顺式构象 在不同多态位点的等位基因之间，因此对于破译协同作用至关重要 多个变体之间的顺式相互作用。单倍型可能在不同的环境中发挥关键作用，包括 连锁分析、关联研究、群体遗传学、医学遗传学和药物遗传学。作为 人类是二倍体生物，如果没有单倍型，遗传信息最终将是不完整的。 最近，针对欧洲血统人群建立了一个大型参考小组（HRC、The 单倍型参考联盟），第一个版本由来自 20 个大群体的 64,976 个单倍型组成。 然而，少数民族人口的单倍型参考面板缺乏。一、少数民族人口 在基因组研究中代表性不足，因此许多非洲人无法获得单倍型 亚群。其次，非洲裔美国人和拉丁裔美国人都是高度混杂的人群， 将他们的基因组塑造成镶嵌基因组。在这些嵌合基因组中，不同的基因组区域 同一个人是从不同种族背景的祖先那里遗传下来的，所以任何单一种族 参考面板不能很好地涵盖用于单倍型定相的混合个体的祖先起源。 第三，由于个体之间的外加剂配方和比例存在巨大差异， 基于已用于同质群体的单倍型频率的定相算法可能 对于非裔美国人和拉丁裔等异质人群效果不佳。在本提案中，我们将 探索应对这些挑战的潜在解决方案。具体来说，我们将战略性地利用大量的 现有的非定相基因型数据集并将其转换为少数群体的单倍型参考； 我们将在网络服务器中实施此参考面板和单倍型定相软件，并将 将 aMAP 软件的本地血统测定组件纳入应用程序包中。目标 的目的是通过解决少数群体中的单倍型参考问题来填补这一空白。