Journal Article

Ancestral paternal genotype controls body weight and food intake for multiple generations

Soha N. Yazbek, Sabrina H. Spiezio, Joseph H. Nadeau and David A. Buchner

in Human Molecular Genetics

Volume 19, issue 21, pages 4134-4144
Published in print November 2010 | ISSN: 0964-6906
Published online August 2010 | e-ISSN: 1460-2083 | DOI:
Ancestral paternal genotype controls body weight and food intake for multiple generations

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Current treatments have largely failed to slow the rapidly increasing world-wide prevalence of obesity and its co-morbidities. Despite a strong genetic contribution to obesity (40–70%), only a small percentage of heritability is explained with current knowledge of monogenic abnormalities, common sequence variants and conventional modes of inheritance. Epigenetic effects are rarely tested in humans because of difficulties arranging studies that distinguish conventional and transgenerational inheritance while simultaneously controlling environmental factors and learned behaviors. However, growing evidence from model organisms implicates genetic and environmental factors in one generation that affect phenotypes in subsequent generations. In this report, we provide the first evidence for paternal transgenerational genetic effects on body weight and food intake. This test focused on the obesity-resistant 6C2d congenic strain, which carries the Obrq2aA/J allele on an otherwise C57BL/6J background. Various crosses between 6C2d and the control C57BL/6J strain showed that the Obrq2aA/J allele in the paternal or grandpaternal generation was sufficient to inhibit diet-induced obesity and reduce food intake in the normally obesity-susceptible, high food intake C57BL/6J strain. These obesity-resistant and reduced food intake phenotypes were transmitted through the paternal lineage but not the maternal lineage with equal strength for at least two generations. Eliminating social interaction between the father and both his offspring and the pregnant dam did not significantly affect food intake levels, demonstrating that the phenotype is transmitted through the male germline rather than through social interactions. Persistence of these phenotypes across multiple generations raises the possibility that transgenerational genetic effects contribute to current metabolic conditions.

Journal Article.  5763 words.  Illustrated.

Subjects: Genetics and Genomics

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