Qahaz, N.; Lone, I.M.; Khadija, A.; Ghnaim, A.; Zohud, O.; Nun, N.B.; Nashef, A.; Abu El-Naaj, I.; Iraqi, F.A. Host Genetic Background Effect on Body Weight Changes Influenced by Heterozygous Smad4 Knockout Using Collaborative Cross Mouse Population. Int. J. Mol. Sci.2023, 24, 16136.
Qahaz, N.; Lone, I.M.; Khadija, A.; Ghnaim, A.; Zohud, O.; Nun, N.B.; Nashef, A.; Abu El-Naaj, I.; Iraqi, F.A. Host Genetic Background Effect on Body Weight Changes Influenced by Heterozygous Smad4 Knockout Using Collaborative Cross Mouse Population. Int. J. Mol. Sci. 2023, 24, 16136.
Qahaz, N.; Lone, I.M.; Khadija, A.; Ghnaim, A.; Zohud, O.; Nun, N.B.; Nashef, A.; Abu El-Naaj, I.; Iraqi, F.A. Host Genetic Background Effect on Body Weight Changes Influenced by Heterozygous Smad4 Knockout Using Collaborative Cross Mouse Population. Int. J. Mol. Sci.2023, 24, 16136.
Qahaz, N.; Lone, I.M.; Khadija, A.; Ghnaim, A.; Zohud, O.; Nun, N.B.; Nashef, A.; Abu El-Naaj, I.; Iraqi, F.A. Host Genetic Background Effect on Body Weight Changes Influenced by Heterozygous Smad4 Knockout Using Collaborative Cross Mouse Population. Int. J. Mol. Sci. 2023, 24, 16136.
Abstract
Background: Obesity and its attendant conditions have become major health problems worldwide and is currently ranked as the fifth most common leading cause of death globally. Complex environmental and genetic factors are the cause of the current obesity epidemic. Diet, lifestyle, chemical exposures, and other confounding factors are difficult to manage in humans. The mice model is helpful in researching genetics BW gain because genetic and environmental risk factors can be controlled in mice. Studies in mouse strains with various genetic backgrounds and established genetic structures provide unparalleled opportunities to find and analyze trait-related genomic loci. In this study, we used the Collaborative Cross (CC), a large panel of recombinant inbred mouse strains, to present a predictive study using CC mice SMAD4 knockout profiles to understand and effectively identify predisposition to body weight gain. Materials and Methods: Male C57Bl / 6J Smad4+/- mice were mated with female mice from 10 different CC lines to create F1 mice (Smad4+/- x CC). Body weight (BW) was measured weekly until week 16, then monthly until the end (week 48). The heritability H2 of the assessed traits was estimated and presented. Comparative analysis of various machine learning algorithms for predicting the BW changes and genotype of mice was conducted. Results and conclusions: Our data showed that the body weight records of F1 mice with different CC lines differed between wildtype and mutant Smad4 mice during the experiment. Genetic background affects weight gain and some lines gained more weight in the presence of Smad4 knockout, while others gained less, but in general, the mutation caused overweight mice, except for a few lines. In both control and mutant groups, female %BW had a higher heritability H2 value than males. Additionally, both sexes with wildtype genotypes showed higher heritability values than the mutant group. Logistic Regression provides the most accurate mouse genotype predictions using machine learning. We plan to validate the proposed method on more CC lines and mice per line to expand machine learning for BW prediction.
Biology and Life Sciences, Biology and Biotechnology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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