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Human genetic polymorphisms, alternative transcripts, and fatty acid nutrition

Tom Brenna
Department of Pediatrics, Dell Medical School
University of Texas
Coverdell, S175
Seminars

Fatty acid nutrition is a major determinant for the predisposition to health, and acute and chronic disease.  Human populations fall into a continuum between the extremes of those subsisting on exclusively terrestrial plant foods ("vegans") and those consuming exclusively meat and seafood.  While all mammals exclusively subsist on an animal food from birth, milk, dietary niches drive metabolic and hence genetic differences between humans just as they drive differences in vegan terrestrial animals (e.g. rabbits) and nearly exclusive carnivores (e.g. cats).  We discovered a human genetic polymorphism, an indel, in the FADS (fatty acid desaturase) gene cluster that determines the circulating levels of the major signaling precursors, arachidonic acid, in free-living humans, as well as all polyunsaturates along the downstream and upstream biochemical pathways.  FADS alternative transcripts control fatty acid abundance, and abnormal fatty acid structures are found in some cancers.  Genetic variation in endogenous fatty acid metabolism and its interaction with diet interact to yield personal dietary requirements for proper development and healthy aging.

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