TY - JOUR
T1 - Mapping novel genetic loci associated with female liver weight variations using Collaborative Cross mice
AU - Abu-Toamih Atamni, Hanifa J.
AU - Botzman, Maya
AU - Mott, Richard
AU - Gat-Viks, Irit
AU - Iraqi, Fuad A.
N1 - Publisher Copyright:
© 2018 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.
PY - 2018/9
Y1 - 2018/9
N2 - 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 (H2) of 0.32 and genetic coefficient of variation (CVG) 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.
AB - 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 (H2) of 0.32 and genetic coefficient of variation (CVG) 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.
KW - Collaborative Cross mouse model
KW - candidate genes
KW - high genetic diverse mouse population
KW - liver weight
KW - quantitative trait locus mapping
KW - standard rodent diet
UR - http://www.scopus.com/inward/record.url?scp=85075102887&partnerID=8YFLogxK
U2 - 10.1002/ame2.12036
DO - 10.1002/ame2.12036
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AN - SCOPUS:85075102887
SN - 2096-5451
VL - 1
SP - 212
EP - 220
JO - Animal Models and Experimental Medicine
JF - Animal Models and Experimental Medicine
IS - 3
ER -