ArticlePLoS biology2021
Predicting novel candidate human obesity genes and their site of action by systematic functional screening in Drosophila.
Article in PLoS biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 20 citations in OpenAlex.
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- A Hypothesis: Metabolic Contributions to 16p11.2 Deletion Syndrome.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Expanding the phenotype and genotype spectrum of TAOK1 neurodevelopmental disorder and delineating TAOK2 neurodevelopmental disorder.Genetics in medicine : official journal of the American College of Medical Genetics · 2025Article
- Interactions between the gut microbiome and DNA methylation patterns in blood and visceral adipose tissue in subjects with different metabolic characteristics.Journal of translational medicine · 2024Article
- Adopting Mechanistic Molecular Biology Approaches in Exposome Research for Causal Understanding.Environmental science & technology · 2024Review
- Body Weight Correlates with Molecular Variances in Patients with Cancer.Cancer research · 2024Article
- Genome-wide screening for genetic variants in polyadenylation signal (PAS) sites in mouse selection lines for fatness and leanness.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Article
- Identification of disease modules using higher-order network structure.Bioinformatics advances · 2023Article
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- Metabolic Syndrome: Lessons from Rodent andBioMed research international · 2022Review
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9 authors at 1 institution in 1 country.
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Abstract
The discovery of human obesity-associated genes can reveal new mechanisms to target for weight loss therapy. Genetic studies of obese individuals and the analysis of rare genetic variants can identify novel obesity-associated genes. However, establishing a functional relationship between these candidate genes and adiposity remains a significant challenge. We uncovered a large number of rare homozygous gene variants by exome sequencing of severely obese children, including those from consanguineous families. By assessing the function of these genes in vivo in Drosophila, we identified 4 genes, not previously linked to human obesity, that regulate adiposity (itpr, dachsous, calpA, and sdk). Dachsous is a transmembrane protein upstream of the Hippo signalling pathway. We found that 3 further members of the Hippo pathway, fat, four-jointed, and hippo, also regulate adiposity and that they act in neurons, rather than in adipose tissue (fat body). Screening Hippo pathway genes in larger human cohorts revealed rare variants in TAOK2 associated with human obesity. Knockdown of Drosophila tao increased adiposity in vivo demonstrating the strength of our approach in predicting novel human obesity genes and signalling pathways and their site of action.
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