Mapping novel genetic loci associated with female liver weight variations using Collaborative Cross mice  

作　　者：Hanifa J.Abu-Toamih Atamni Maya Botzman Richard Mott Irit Gat-Viks Fuad A.Iraqi 

机构地区：[1]Sackler Faculty of Medicine, Tel-Aviv University [2]Faculty of Life Sciences, Tel-Aviv University [3]Department of Genetics, University College of London

出　　处：《Animal Models and Experimental Medicine》2018年第3期212-220,共9页动物模型与实验医学（英文）

基　　金：Israeli Centers of Research Excellence;Wellcome Trust,Grant/Award Number:085906/Z/08/Z,075491/Z/04,090532/Z/09/Z;Edmond J.Safra Center for Bioinformatics at Tel-Aviv University;Tel-Aviv University

摘　　要：Background: Liver weight is a complex trait, controlled by polygenic factors and differs within populations. Dissecting the genetic architecture underlying these variations will facilitate the search for key role candidate genes involved directly in the hepatomegaly process and indirectly involved in related diseases etiology.Methods: Liver weight of 506 mice generated from 39 different Collaborative Cross(CC) lines with both sexes at age 20 weeks old was determined using an electronic balance. Genomic DNA of the CC lines was genotyped with high-density single nucleotide polymorphic markers.Results: Statistical analysis revealed a significant(P < 0.05) variation of liver weight between the CC lines, with broad sense heritability(H^2) of 0.32 and genetic coefficient of variation(CV_G) of 0.28. Subsequently, quantitative trait locus(QTL) mapping was performed, and results showed a significant QTL only for females on chromosome 8 at genomic interval 88.61-93.38 Mb(4.77 Mb). Three suggestive QTL were mapped at chromosomes 4, 12 and 13. The four QTL were designated as LWL1-LWL4 referring to liver weight loci 1-4 on chromosomes 8, 4, 12 and 13,respectively.Conclusion: To our knowledge, this report presents, for the first time, the utilization of the CC for mapping QTL associated with baseline liver weight in mice. Our findings demonstrate that liver weight is a complex trait controlled by multiple genetic factors that differ significantly between sexes.Background: Liver weight is a complex trait, controlled by polygenic factors and differs within populations. Dissecting the genetic architecture underlying these variations will facilitate the search for key role candidate genes involved directly in the hepatomegaly process and indirectly involved in related diseases etiology.Methods: Liver weight of 506 mice generated from 39 different Collaborative Cross(CC) lines with both sexes at age 20 weeks old was determined using an electronic balance. Genomic DNA of the CC lines was genotyped with high-density single nucleotide polymorphic markers.Results: Statistical analysis revealed a significant(P < 0.05) variation of liver weight between the CC lines, with broad sense heritability(H^2) of 0.32 and genetic coefficient of variation(CV_G) of 0.28. Subsequently, quantitative trait locus(QTL) mapping was performed, and results showed a significant QTL only for females on chromosome 8 at genomic interval 88.61-93.38 Mb(4.77 Mb). Three suggestive QTL were mapped at chromosomes 4, 12 and 13. The four QTL were designated as LWL1-LWL4 referring to liver weight loci 1-4 on chromosomes 8, 4, 12 and 13,respectively.Conclusion: To our knowledge, this report presents, for the first time, the utilization of the CC for mapping QTL associated with baseline liver weight in mice. Our findings demonstrate that liver weight is a complex trait controlled by multiple genetic factors that differ significantly between sexes.

关 键 词：candidate genes COLLABORATIVE CROSS MOUSE model high genetic diverse MOUSE population liver weight quantitative TRAIT locus MAPPING standard RODENT diet 

分 类 号：R[医药卫生]