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The genomic basis of environmental adaptation in mice

小鼠环境适应的基因组基础

基本信息

批准号：
10166869
负责人：
MICHAEL W. NACHMAN
金额：
$ 33.45万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-21 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10166869
关键词：
Age Alberta province Alleles Americas Arizona Biology Blood Chemical Analysis Body Size Body mass index Brazil Candidate Disease Gene Chromosome Mapping Climate Complex Disease Ear Environment Evolution Exhibits Florida Foundations Gene Expression Gene Expression Profile Gene Expression Regulation Generations Genes Genetic Genetic Variation Genetic study Genome Scan Genomic Segment Genomics Genotype Geography Goals Health House mice Human Inbreeding Individual Laboratories Limb structure Link Linkage Disequilibrium Mapping Liver Mammals Maps Measures Metabolic Metabolic Diseases Metabolism Modeling Morphology Mus New York North America Pattern Phenotype Physiology Population Population Genetics Quantitative Genetics Quantitative Trait Loci RNA Sequences Research Resolution Role Sampling South America Structure Study models Surveys System Tail Testing Tissues Variant Western Europe Work environmental adaptation exome experimental study genetic approach genomic data insight novel trait whole genome

项目摘要

PROJECT SUMMARY Much of our understanding of the genetic basis of adaptation derives from studies of simple traits in which a large proportion of the phenotypic variation is controlled by one or a few genes of major effect. However, much of evolution involves changes in complex traits that are controlled by many genes of small to modest effect. Complex traits also underlie most phenotypic differences among humans, including those related to human health. The proposed research will study the genetic basis of environmental adaptation in house mice, Mus musculus, the best mammalian model for humans. House mice have recently expanded into the Americas from their native range in Western Europe. By combining studies of genetic and phenotypic variation in natural populations with crosses in the lab, this project will make explicit links between genotype and phenotype for several complex traits. This work will utilize recent large-scale surveys of 20 populations of house mice collected across the Americas from 55° S latitude to 54° N latitude. New inbred lines of mice from different environments will be used to measure phenotypes in a common laboratory environment and to perform controlled crosses. Mice from colder environments in the Americas have evolved to become larger (Bergmann's rule) and have shorter extremities (Allen's rule), conforming to two of the best-documented eco- geographic patterns in mammals. In addition, mice from different environments differ in many metabolic traits, including activity levels, body mass index, and aspects of blood chemistry. Here, we build on a recent genome-scan for selection among 50 mice in Eastern North America in four ways. (1) Exomes will be sequenced at moderate coverage and whole genomes will be sequenced at low coverage in an additional 150 mice from two transects, one in Western North America and one in South America, to identify loci underlying environmental adaptation using models that account for population structure. Replicated patterns in separate transects will provide additional evidence of selection. (2) Patterns of gene expression will be studied in both wild-caught mice and in laboratory crosses. Identification of cis-acting expression quantitative trait loci (cis- eQTL) will help pinpoint genes underlying adaptation. (3) Loci underlying phenotypic differences will be mapped using laboratory crosses of progeny derived from mice from different environments. (4) Finally, association studies will be conducted in two populations to more precisely map specific genes underlying phenotypic traits. Associations will also be used in combination with estimates of allele age to test polygenic modes of adaptation for several traits. Together, laboratory crosses and association studies will provide links between genotype and phenotype with resolution at the level of individual genes. The combination of quantitative-genetic and population-genetic approaches in this study will identify loci underlying polygenic adaptation in mice and will identify the genetic basis of traits likely to be relevant for understanding metabolic differences among humans.

项目总结