Document Detail


Genetic adaptation of fatty-acid metabolism: a human-specific haplotype increasing the biosynthesis of long-chain omega-3 and omega-6 fatty acids.
MedLine Citation:
PMID:  22503634     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Omega-3 and omega-6 long-chain polyunsaturated fatty acids (LC-PUFAs) are essential for the development and function of the human brain. They can be obtained directly from food, e.g., fish, or synthesized from precursor molecules found in vegetable oils. To determine the importance of genetic variability to fatty-acid biosynthesis, we studied FADS1 and FADS2, which encode rate-limiting enzymes for fatty-acid conversion. We performed genome-wide genotyping (n = 5,652 individuals) and targeted resequencing (n = 960 individuals) of the FADS region in five European population cohorts. We also analyzed available genomic data from human populations, archaic hominins, and more distant primates. Our results show that present-day humans have two common FADS haplotypes-defined by 28 closely linked SNPs across 38.9 kb-that differ dramatically in their ability to generate LC-PUFAs. No independent effects on FADS activity were seen for rare SNPs detected by targeted resequencing. The more efficient, evolutionarily derived haplotype appeared after the lineage split leading to modern humans and Neanderthals and shows evidence of positive selection. This human-specific haplotype increases the efficiency of synthesizing essential long-chain fatty acids from precursors and thereby might have provided an advantage in environments with limited access to dietary LC-PUFAs. In the modern world, this haplotype has been associated with lifestyle-related diseases, such as coronary artery disease.
Authors:
Adam Ameur; Stefan Enroth; Asa Johansson; Ghazal Zaboli; Wilmar Igl; Anna C V Johansson; Manuel A Rivas; Mark J Daly; Gerd Schmitz; Andrew A Hicks; Thomas Meitinger; Lars Feuk; Cornelia van Duijn; Ben Oostra; Peter P Pramstaller; Igor Rudan; Alan F Wright; James F Wilson; Harry Campbell; Ulf Gyllensten
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-04-12
Journal Detail:
Title:  American journal of human genetics     Volume:  90     ISSN:  1537-6605     ISO Abbreviation:  Am. J. Hum. Genet.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-07     Completed Date:  2012-06-25     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0370475     Medline TA:  Am J Hum Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  809-20     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Adaptation, Physiological
Amino Acid Sequence
Animals
Croatia
Cross-Sectional Studies
Diet
European Continental Ancestry Group / genetics
Fatty Acid Desaturases / genetics*,  metabolism
Fatty Acids, Omega-3 / metabolism*
Fatty Acids, Omega-6 / metabolism*
Haplotypes*
Humans
Italy
Life Style
Molecular Sequence Data
Multigene Family
Neanderthals
Phylogeography
Polymorphism, Single Nucleotide
Risk Factors
Scotland
Sequence Analysis, DNA
Sweden
Grant Support
ID/Acronym/Agency:
CZB/4/710//Chief Scientist Office; MC_PC_U127561128//Medical Research Council; MC_U127561128//Medical Research Council
Chemical
Reg. No./Substance:
0/Fatty Acids, Omega-3; 0/Fatty Acids, Omega-6; EC 1.14.19.-/Fatty Acid Desaturases; EC 1.14.19.3/FADS2 protein, human; EC 1.14.99.-/delta-5 fatty acid desaturase
Comments/Corrections

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