Abstract
BackgroundLiver 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.MethodsLiver 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.ResultsStatistical 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 (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.ConclusionTo 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.
Highlights
Liver weight is a complex trait, controlled by polygenic factors and differs within populations
We present, for the first time precise mapping of sex‐specific quantitative trait locus (QTL) influencing the baseline liver weight phenotypic variations of female mice generated from 24 Collaborative Cross (CC) lines
Considering the accumulated evidence for significant sex differences at baseline traits/disease etiology, and based on our previous studies where we demonstrated the significant sex differences observed between sexes within the CC lines,[34,35,76] we have included both sexes in our current analysis
Summary
All experimental mice and protocols were approved by the Institutional Animal Care and Use Committee M‐10‐073 and M‐14‐ 007) of Tel‐Aviv University (TAU), which adhered to the Israeli guidelines that follow the National Institutes of Health of USA animal care and use protocols. Full details of the development of these CC lines are given in previous reports.[50,51] The study cohort consisted of 506 mice, generated from 39 different CC lines, from which 22 CC lines were selected with representation of both sexes. The mice were given tap water and standard rodent chow diet ad libitum, which consists of %Kcal from 18% fat, 24% protein and 58% carbohydrates (TD.2018SC; Teklad Global, Harlan, Madison, WI, USA), since weaning at the age of 3 weeks until the age of 20 weeks. Thereafter, mice were dissected and livers collected, and the liver weight of each mouse was determined using an electronic balance
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