Document Detail

Ancestral paternal genotype controls body weight and food intake for multiple generations.
MedLine Citation:
PMID:  20696673     Owner:  NLM     Status:  MEDLINE    
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 Obrq2a(A/J) allele on an otherwise C57BL/6J background. Various crosses between 6C2d and the control C57BL/6J strain showed that the Obrq2a(A/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.
Soha N Yazbek; Sabrina H Spiezio; Joseph H Nadeau; David A Buchner
Related Documents :
15004433 - Effect of neonatal handling and sex on basal and chronic stress-induced corticosterone ...
12027273 - Epidemiological and nutritional transition in mexico: rapid increase of non-communicabl...
4033063 - Non-neoplastic lesions of female virgin han:nmri mice, incidence and influence of food ...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-08-09
Journal Detail:
Title:  Human molecular genetics     Volume:  19     ISSN:  1460-2083     ISO Abbreviation:  Hum. Mol. Genet.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-11     Completed Date:  2011-02-10     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  4134-44     Citation Subset:  IM    
Department of Genetics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Body Weight / genetics*
Energy Intake / genetics*
Epigenesis, Genetic
Genomic Imprinting
Germ Cells
Litter Size
Mice, Inbred C57BL
Obesity / genetics
Polymorphism, Genetic
Grant Support

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Cardiac defects contribute to the pathology of spinal muscular atrophy models.
Next Document:  An exact method for link parameter estimation in error benchmarking: an application to Phase II two-...