• Sirui Zhou, Lan Xiong, Pingxing Xie, Amirthagowri Ambalavanan, Cynthia V Bourassa, Alexandre Dionne-Laporte, Dan Spiegelman, Maude Turcotte Gauthier, Edouard Henrion, Ousmane Diallo, Patrick A Dion, and Guy A Rouleau.
• Montreal Neurological Institute and Hospital, McGill University, Montréal (Que), Canada; Département de médecine, Faculté de médecine, Université de Montréal, Montréal (Que), Canada.
• Plos One. 2015 Jan 1; 10 (5): e0128255.

BackgroundNunavik Inuit (northern Quebec, Canada) reside along the arctic coastline where for generations their daily energy intake has mainly been derived from animal fat. Given this particular diet it has been hypothesized that natural selection would lead to population specific allele frequency differences and unique variants in genes related to fatty acid metabolism. A group of genes, namely CPT1A, CPT1B, CPT1C, CPT2, CRAT and CROT, encode for three carnitine acyltransferases that are important for the oxidation of fatty acids, a critical step in their metabolism.MethodsExome sequencing and SNP array genotyping were used to examine the genetic variations in the six genes encoding for the carnitine acyltransferases in 113 Nunavik Inuit individuals.ResultsAltogether ten missense variants were found in genes CPT1A, CPT1B, CPT1C, CPT2 and CRAT, including three novel variants and one Inuit specific variant CPT1A p.P479L (rs80356779). The latter has the highest frequency (0.955) compared to other Inuit populations. We found that by comparison to Asians or Europeans, the Nunavik Inuit have an increased mutation burden in CPT1A, CPT2 and CRAT; there is also a high level of population differentiation based on carnitine acyltransferase gene variations between Nunavik Inuit and Asians.ConclusionThe increased number and frequency of deleterious variants in these fatty acid metabolism genes in Nunavik Inuit may be the result of genetic adaptation to their diet and/or the extremely cold climate. In addition, the identification of these variants may help to understand some of the specific health risks of Nunavik Inuit.

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