ETHNOS: A versatile electronic tool for the development and curation of national genetic databases

National and ethnic mutation databases (NEMDBs) are emerging online repositories, recording extensive information about the described genetic heterogeneity of an ethnic group or population. These resources facilitate the provision of genetic services and provide a comprehensive list of genomic variations among different populations. As such, they enhance awareness of the various genetic disorders. Here, we describe the features of the ETHNOS software, a simple but versatile tool based on a flat-file database that is specifically designed for the development and curation of NEMDBs. ETHNOS is a freely available softw

ETHNOS : A versatile electronic tool for the development and curation of national genetic databases.

National and ethnic mutation databases (NEMDBs) are emerging online repositories, recording extensive information about the described genetic heterogeneity of an ethnic group or population. These resources facilitate the provision of genetic services and provide a comprehensive list of genomic variations among different populations. As such, they enhance awareness of the various genetic disorders. Here, we describe the features of the ETHNOS software, a simple but versatile tool based on a flat-file database that is specifically designed for the development and curation of NEMDBs. ETHNOS is a freely available software which runs more than half of the NEMDBs currently available. Given the emerging need for NEMDB in genetic testing services and the fact that ETHNOS is the only off-the-shelf software available for NEMDB development and curation, its adoption in subsequent NEMDB development would contribute towards data content uniformity, unlike the diverse contents and quality of the available gene (locus)-specific databases. Finally, we allude to the potential applications of NEMDBs, not only as worldwide central allele frequency repositories, but also, and most importantly, as data warehouses of individual-level genomic data, hence allowing for a comprehensive ethnicity-specific documentation of genomic variation

Expression of Fgf21 in liver and serum after simvastatin treatment in mice.

<p><b>A.</b> Immunoblotting analysis of Fgf21 in the livers of 3-month old male mice treated with simvastatin (0.1% w/w in chow) for 1 week. Immunoblots for Ampkα and elf2a and Coomassie blue staining of the gel were used as loading controls. <b>B.</b> Relative Fgf21 protein levels as assessed by immunoblotting after normalization to elf2a levels. Data are presented as the mean ± SEM. n = 5 per treatment. *P<0.05. <b>C, D, E, F, G, H</b>. mRNA levels of Fgf21(C), Hmgcr (D), Pcsk9 (E), Acox1 (F), Cyp4a10 (G), Cyp7a1 (H) in the livers of 3-month old male mice treated with simvastatin (0.1% w/w in chow) for 1 week. Relative mRNA levels were assessed by qRT-PCR. Data are presented as the mean ±SEM. n = 7–8 per treatment. *P<0.05. <b>I.</b> Assessment of serum Fgf21 levels by ELISA in 3-month old male mice treated with vehicle or simvastatin. Data are presented as the mean ±SEM. n = 7–8 per treatment. *P<0.05.</p

Body weights, food consumption and hepatic Fgf21 mRNA levels in 1-month old male mice following the administration of increasing doses of simvastatin for 1 week.

<p><b>A.</b> Body weights of mice before and after exposure to simvastatin expressed as the % of initial weight. *P<0.05 compared with baseline weight. <b>B.</b> Cumulative food intake for the 1-week treatment with simvastatin. *P<0.05 compared with vehicle treatment (0% simvastatin w/w). <b>C.</b> Fgf21 hepatic mRNA levels as assessed by qRT-PCR. *P<0.05 compared with the 0% dose. a, b, c, d, e denote 0%, 0.01%, 0.05%, 0.1% and 0.5% w/w simvastatin in chow, respectively. For panels A, B, C the data are presented as the mean ± SEM. n = 6 per treatment with the exception of the 0.5% dose (n = 3; 5 mice received the treatment and 2 died after the treatment).</p

mRNA levels of Fgf21 and relevant genes in mouse primary hepatocytes after simvastatin treatment.

<p>mRNA levels of Fgf21 (<b>A</b>), Pcsk9 (<b>B</b>), Acox1 (<b>C</b>), Cyp4a10 (<b>D</b>) in primary hepatocytes treated with vehicle or simvastatin (3 different doses) for 12 hours. Data are presented as the means ±SEM from 3 individual experiments, each of which included 3 technical replicates. *P<0.05 (compared with vehicle treatment).</p

Primer sequences used for qRT-PCR.

<p>Primer sequences used for qRT-PCR.</p

mRNA levels of Fgf21 in primary hepatocytes and HepG2 cells after overexpression of Srebp-2 or miR-33.

<p>Srebp-2 (<b>A</b>) and Fgf21 (<b>B</b>) mRNA levels in primary hepatocytes after overexpression of Srebp-2. Data are presented as the means ±SEM from 3 individual experiments, each of which included 3 technical replicates. *P<0.05 (compared with empty vector transfection). LDLR (<b>C</b>) and FGF21 (<b>D</b>) mRNA levels in HepG2 cells after overexpression of Srebp-2. Data are presented as the means ±SEM from 6 individual experiments, each of which included 3 technical replicates. *P<0.05 (compared with empty vector transfection). ABCA1 (<b>E</b>) and FGF21 (<b>F</b>) mRNA levels in HepG2 cells after overexpression of miR-33. Data are presented as the means ±SEM from 3 individual experiments, each of which included 3 technical replicates. *P<0.05 (compared with empty vector transfection).</p

Fgf21 mRNA levels after intraperitoneal administration of simvastatin.

<p>Fgf21 (<b>A</b>) and Pcsk9 (<b>B</b>) mRNA levels in the liver of mice administered vehicle (control) or simvastatin intraperitoneally twice (20 and 12 hours before sacrifice). Data are presented as the mean ± SEM, n = 10 per treatment. *P<0.05 compared with control.</p