Drivers and health implications of the dietary transition among Inuit in the Canadian Arctic : a scoping review

Objective: The current study undertook a systematic scoping review on the drivers and implications of dietary changes among Inuit in the Canadian Arctic. Design: A keyword search of peer-reviewed articles was performed using PubMed, Web of Science, CINAHL, Academic Search Premier, Circumpolar Health Bibliographic Database and High North Research Documents. Eligibility criteria included all full-text articles of any design reporting on research on food consumption, nutrient intake, dietary adequacy, dietary change, food security, nutrition-related chronic diseases or traditional food harvesting and consumption among Inuit populations residing in Canada. Articles reporting on in vivo and in vitro experiments or on health impacts of environmental contaminants were excluded. Results: A total of 162 studies were included. Studies indicated declining country food (CF) consumption in favour of market food (MF). Drivers of this transition include colonial processes, poverty and socio-economic factors, changing food preferences and knowledge, and climate change. Health implications of the dietary transition are complex. Micro-nutrient deficiencies and dietary inadequacy are serious concerns and likely exacerbated by increased consumption of non-nutrient dense MF. Food insecurity, overweight, obesity and related cardiometabolic health outcomes are growing public health concerns. Meanwhile, declining CF consumption is entangled with shifting culture and traditional knowledge, with potential implications for psychological, spiritual, social and cultural health and well-being. Conclusions: By exploring and synthesising published literature, this review provides insight into the complex factors influencing Inuit diet and health. Findings may be informative for future research, decision-making and intersectoral actions around risk assessment, food policy and innovative community programmes

Mutation-specific pathophysiological mechanisms define different neurodevelopmental disorders associated with SATB1 dysfunction.

Whereas large-scale statistical analyses can robustly identify disease-gene relationships, they do not accurately capture genotype-phenotype correlations or disease mechanisms. We use multiple lines of independent evidence to show that different variant types in a single gene, SATB1, cause clinically overlapping but distinct neurodevelopmental disorders. Clinical evaluation of 42 individuals carrying SATB1 variants identified overt genotype-phenotype relationships, associated with different pathophysiological mechanisms, established by functional assays. Missense variants in the CUT1 and CUT2 DNA-binding domains result in stronger chromatin binding, increased transcriptional repression, and a severe phenotype. In contrast, variants predicted to result in haploinsufficiency are associated with a milder clinical presentation. A similarly mild phenotype is observed for individuals with premature protein truncating variants that escape nonsense-mediated decay, which are transcriptionally active but mislocalized in the cell. Our results suggest that in-depth mutation-specific genotype-phenotype studies are essential to capture full disease complexity and to explain phenotypic variability

Mutation-specific pathophysiological mechanisms define different neurodevelopmental disorders associated with SATB1 dysfunction

International audienceWhereas large-scale statistical analyses can robustly identify disease-gene relationships, they do not accurately capture genotype-phenotype correlations or disease mechanisms. We use multiple lines of independent evidence to show that different variant types in a single gene, SATB1, cause clinically overlapping but distinct neurodevelopmental disorders. Clinical evaluation of 42 individuals carrying SATB1 variants identified overt genotype-phenotype relationships, associated with different pathophysiological mechanisms, established by functional assays. Missense variants in the CUT1 and CUT2 DNA-binding domains result in stronger chromatin binding, increased transcriptional repression, and a severe phenotype. In contrast, variants predicted to result in haploinsufficiency are associated with a milder clinical presentation. A similarly mild phenotype is observed for individuals with premature protein truncating variants that escape nonsense-mediated decay, which are transcriptionally active but mislocalized in the cell. Our results suggest that in-depth mutation-specific genotype-phenotype studies are essential to capture full disease complexity and to explain phenotypic variability