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

Abu‐Toamih Atamni, Hanifa J.; Botzman, Maya; Mott, Richard; Gat‐Viks, Irit; Iraqi, Fuad A.

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.