Scoring the collective effects of SNPs: association of minor alleles with complex traits in model organisms  

作　　者：YUAN DeJian ZHU ZuoBin TAN XiaoHua LIANG Jie ZENG Chen ZHANG JieGen CHEN Jun MA Long DOGAN Ayca BROCKMANN Gudrun GOLDMANN Oliver MEDINA Eva RICE Amanda D. MOYER Richard W. MAN Xian YI Ke LI YanKe LU Qing HUANG YiMin HUANG Shi 

机构地区：[1]State Key Laboratory of Medical Genetics, Central South University [2]High Performance Computing Center, Modern Educational Technology Center, New Campus, Central South University [3]Department of Crop and Animal Sciences, Faculty of Agriculture and Horticulture, Humboldt-Universitt zu Berlin,Invalidenstraβe 42,Berlin 10115, Germany [4]Infection Immunology Group, Helmholtz Centre for Infection Research, Inhoffenstrae 7,Braunschweig 38124, Germany [5]Department of Molecular Genetics and Microbiology, University of Florida

出　　处：《Science China(Life Sciences)》2014年第9期876-888,共13页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China(81171880);the National Basic Research Program of China(2011CB51001 to S.Huang);the GeNeSys Consortium(to O.Goldmann and E.Medina

摘　　要：It has long been assumed that most parts of a genome and most genetic variations or SNPs are non-functional with regard to reproductive fitness.However,the collective effects of SNPs have yet to be examined by experimental science.We here developed a novel approach to examine the relationship between traits and the total amount of SNPs in panels of genetic reference populations.We identified the minor alleles(MAs)in each panel and the MA content(MAC)that each inbred strain carried for a set of SNPs with genotypes determined in these panels.MAC was nearly linearly linked to quantitative variations in numerous traits in model organisms,including life span,tumor susceptibility,learning and memory,sensitivity to alcohol and anti-psychotic drugs,and two correlated traits poor reproductive fitness and strong immunity.These results suggest that the collective effects of SNPs are functional and do affect reproductive fitness.It has long been assumed that most parts of a genome and most genetic variations or SNPs are non-functional with regard to reproductive fitness. However, the collective effects of SNPs have yet to be examined by experimental science. We here de- veloped a novel approach to examine the relationship between traits and the total amount of SNPs in panels of genetic refer- ence populations. We identified the minor alleles （MAs） in each panel and the MA content （MAC） that each inbred strain car- ried for a set of SNPs with genotypes determined in these panels. MAC was nearly linearly linked to quantitative variations in numerous traits in model organisms, including life span, tumor susceptibility, learning and memory, sensitivity to alcohol and anti-psychotic drugs, and two correlated traits poor reproductive fitness and strong immunity. These results suggest that the collective effects of SNPs are functional and do affect reproductive fitness.

关 键 词：collective effects complex traits minor alleles SNPS recombinant inbred lines minor allele content(MAC) 

分 类 号：R394[医药卫生—医学遗传学]