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  Analysis of Genes Involved in Body Weight Regulation by Targeted Re-Sequencing

Volckmar, A. L., Han, C. T., Putter, C., Haas, S., Vogel, C. I., Knoll, N., et al. (2016). Analysis of Genes Involved in Body Weight Regulation by Targeted Re-Sequencing. PLoS One, 11(2): e0147904. doi:10.1371/journal.pone.0147904.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-44E6-3 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002D-44E7-1
Genre: Journal Article

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© 2016 Volckmar et al

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 Creators:
Volckmar, A. L., Author
Han, C. T., Author
Putter, C., Author
Haas, S.1, Author              
Vogel, C. I., Author
Knoll, N., Author
Struve, C., Author
Gobel, M., Author
Haas, K., Author
Herrfurth, N., Author
Jarick, I., Author
Grallert, H., Author
Schurmann, A., Author
Al-Hasani, H., Author
Hebebrand, J., Author
Sauer, S., Author
Hinney, A., Author
Affiliations:
1Gene Structure and Array Design (Stefan Haas), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479640              

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Free keywords: Adolescent Adult Body Weight/*genetics Child Computer Simulation DNA Mutational Analysis Female *Gene Expression Regulation Genetic Predisposition to Disease Heterozygote High-Throughput Nucleotide Sequencing/*methods Humans Linkage Disequilibrium/genetics Male Obesity/genetics Quality Control Reproducibility of Results Thinness/genetics
 Abstract: INTRODUCTION: Genes involved in body weight regulation that were previously investigated in genome-wide association studies (GWAS) and in animal models were target-enriched followed by massive parallel next generation sequencing. METHODS: We enriched and re-sequenced continuous genomic regions comprising FTO, MC4R, TMEM18, SDCCAG8, TKNS, MSRA and TBC1D1 in a screening sample of 196 extremely obese children and adolescents with age and sex specific body mass index (BMI) >/= 99th percentile and 176 lean adults (BMI </= 15th percentile). 22 variants were confirmed by Sanger sequencing. Genotyping was performed in up to 705 independent obesity trios (extremely obese child and both parents), 243 extremely obese cases and 261 lean adults. RESULTS AND CONCLUSION: We detected 20 different non-synonymous variants, one frame shift and one nonsense mutation in the 7 continuous genomic regions in study groups of different weight extremes. For SNP Arg695Cys (rs58983546) in TBC1D1 we detected nominal association with obesity (pTDT = 0.03 in 705 trios). Eleven of the variants were rare, thus were only detected heterozygously in up to ten individual(s) of the complete screening sample of 372 individuals. Two of them (in FTO and MSRA) were found in lean individuals, nine in extremely obese. In silico analyses of the 11 variants did not reveal functional implications for the mutations. Concordant with our hypothesis we detected a rare variant that potentially leads to loss of FTO function in a lean individual. For TBC1D1, in contrary to our hypothesis, the loss of function variant (Arg443Stop) was found in an obese individual. Functional in vitro studies are warranted.

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Language(s): eng - English
 Dates: 2016-02-012016
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1371/journal.pone.0147904
ISSN: 1932-6203 (Electronic)1932-6203 (Linking)
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Title: PLoS One
Source Genre: Journal
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Publ. Info: San Francisco, CA : Public Library of Science
Pages: - Volume / Issue: 11 (2) Sequence Number: e0147904 Start / End Page: - Identifier: ISSN: 1932-6203
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000277850