title: Increased missense mutation burden of Fatty Acid metabolism related genes in nunavik inuit population.
abstract: BACKGROUND
  Nunavik 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.
  
  
  METHODS
  Exome 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.
  
  
  RESULTS
  Altogether 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Montreal Neurological Institute and Hospital, McGill University, Montréal (Que), Canada; Département de médecine, Faculté de médecine, Université de Montréal, Montréal (Que), Canada.
authors.forename: Sirui
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Département de psychiatrie, Faculté de médecine, Université de Montréal, Montréal (Que), Canada; Centre de recherche, Institut universitaire en santé mentale de Montréal (Que), Canada.
authors.forename: Lan
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Montreal Neurological Institute and Hospital, McGill University, Montréal (Que), Canada; Department of Human Genetics, McGill University, Montréal (Que), Canada.
authors.forename: Pingxing
authors.initials: P
authors.lastname: Xie
authors.affiliation: Montreal Neurological Institute and Hospital, McGill University, Montréal (Que), Canada; Department of Human Genetics, McGill University, Montréal (Que), Canada.
authors.forename: Amirthagowri
authors.initials: A
authors.lastname: Ambalavanan
authors.affiliation: Montreal Neurological Institute and Hospital, McGill University, Montréal (Que), Canada.
authors.forename: Cynthia V
authors.initials: CV
authors.lastname: Bourassa
authors.affiliation: Montreal Neurological Institute and Hospital, McGill University, Montréal (Que), Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Dionne-Laporte
authors.affiliation: Montreal Neurological Institute and Hospital, McGill University, Montréal (Que), Canada.
authors.forename: Dan
authors.initials: D
authors.lastname: Spiegelman
authors.affiliation: Montreal Neurological Institute and Hospital, McGill University, Montréal (Que), Canada.
authors.forename: Maude
authors.initials: M
authors.lastname: Turcotte Gauthier
authors.affiliation: Montreal Neurological Institute and Hospital, McGill University, Montréal (Que), Canada.
authors.forename: Edouard
authors.initials: E
authors.lastname: Henrion
authors.affiliation: Montreal Neurological Institute and Hospital, McGill University, Montréal (Que), Canada.
authors.forename: Ousmane
authors.initials: O
authors.lastname: Diallo
authors.affiliation: Montreal Neurological Institute and Hospital, McGill University, Montréal (Que), Canada; Department of Neurology and Neurosurgery, McGill University, Montréal (Que), Canada.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Dion
authors.affiliation: Montreal Neurological Institute and Hospital, McGill University, Montréal (Que), Canada; Department of Neurology and Neurosurgery, McGill University, Montréal (Que), Canada.
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
mesh_terms: D002333:Carnitine Acyltransferases / Q000235:genetics* / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D059472:Exome; D005227:Fatty Acids / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D004930:Inuit / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010084:Oxidation-Reduction; D020641:Polymorphism, Single Nucleotide; D011792:Quebec
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D002333:Carnitine Acyltransferases