Summary of Study ST000999

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000676. The data can be accessed directly via it's Project DOI: 10.21228/M8968S This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST000999
Study TitleNatural genetic variation in C. elegans identified genomic loci controlling metabolite levels
Study TypeMetabolomics in C. elegans
Study SummaryMetabolic homeostasis is sustained by complex biological networks that respond to nutrient availability. Genetic and environmental factors may disrupt this equilibrium leading to metabolic disorders, including obesity and type 2 diabetes. To identify the genetic factors controlling metabolism, we performed quantitative genetic analysis using a population of 199 recombinant inbred lines (RILs) in the nematode Caenorhabditis elegans. We focused on the genomic regions that control metabolite levels by measuring fatty acid (FA) and amino acid (AA) composition in the RILs using targeted metabolomics. The genetically diverse RILs showed a large variation in their FA and AA levels with a heritability ranging from 32-82%. We detected strongly co-correlated metabolite clusters and 36 significant metabolite QTL (mQTL). We focused on mQTL displaying highly significant linkage and heritability, including an mQTL for the FA C14:1 on Chromosome I, and another mQTL for the FA C18:2 on Chromosome IV. Using introgression lines (ILs) we were able to narrow down both mQTL to a 1.4 Mbp and a 3.6 Mbp region, respectively. RNAi-based screening focusing on the Chromosome I mQTL identified several candidate genes for the C14:1 mQTL, including lagr-1, Y87G2A.2, nhr-265, nhr-276, and nhr-81. Overall, this systems approach provides us with a powerful platform to study the genetic basis of C. elegans metabolism. Furthermore, it allows us to investigate interventions, such as nutrients and stresses that maintain or disturb the regulatory network controlling metabolic homeostasis, and identify gene-by-environment interactions.
Institute
Academic Medical Center of Amsterdam
Last NameGao
First NameArwen
AddressMeibergdreef 9, Amsterdam, North-Holland, 1105 AZ, Netherlands
Emailw.gao@amc.nl
Phone0031205663827
Submit Date2018-07-05
Analysis Type DetailLC-MS
Release Date2018-07-13
Release Version1
Arwen Gao Arwen Gao
https://dx.doi.org/10.21228/M8968S
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR000676
Project DOI:doi: 10.21228/M8968S
Project Title:Natural genetic variation in C. elegans identified genomic loci controlling metabolite levels
Project Type:Targeted metabolomics analysis
Project Summary:Metabolic homeostasis is sustained by complex biological networks that respond to nutrient availability. Genetic and environmental factors may disrupt this equilibrium leading to metabolic disorders, including obesity and type 2 diabetes. To identify the genetic factors controlling metabolism, we performed quantitative genetic analysis using a population of 199 recombinant inbred lines (RILs) in the nematode Caenorhabditis elegans. We focused on the genomic regions that control metabolite levels by measuring fatty acid (FA) and amino acid (AA) composition in the RILs using targeted metabolomics. The genetically diverse RILs showed a large variation in their FA and AA levels with a heritability ranging from 32-82%. We detected strongly co-correlated metabolite clusters and 36 significant metabolite QTL (mQTL). We focused on mQTL displaying highly significant linkage and heritability, including an mQTL for the FA C14:1 on Chromosome I, and another mQTL for the FA C18:2 on Chromosome IV. Using introgression lines (ILs) we were able to narrow down both mQTL to a 1.4 Mbp and a 3.6 Mbp region, respectively. RNAi-based screening focusing on the Chromosome I mQTL identified several candidate genes for the C14:1 mQTL, including lagr-1, Y87G2A.2, nhr-265, nhr-276, and nhr-81. Overall, this systems approach provides us with a powerful platform to study the genetic basis of C. elegans metabolism. Furthermore, it allows us to investigate interventions, such as nutrients and stresses that maintain or disturb the regulatory network controlling metabolic homeostasis, and identify gene-by-environment interactions.
Institute:Academic Medical Center of Amsterdam
Last Name:Gao
First Name:Arwen
Address:Meibergdreef 9, Amsterdam, North-Holland, 1105 AZ, Netherlands
Email:w.gao@amc.nl
Phone:0031205663827

Subject:

Subject ID:SU001038
Subject Type:Other
Subject Species:Caenorhabditis elegans
Taxonomy ID:6239
Age Or Age Range:young adult
Gender:Hermaphrodite
Species Group:Recombinant inbred lines

Factors:

Subject type: Other; Subject species: Caenorhabditis elegans (Factor headings shown in green)

mb_sample_id local_sample_id Strain type
SA061777WN252_b4_9Introgression line
SA061778cbn089_b4_9Introgression line
SA061779WN252_b3_9Introgression line
SA061780WN252_b2_9Introgression line
SA061781WN251_b3_9Introgression line
SA061782WN252_b1_9Introgression line
SA061783cbn089_b3_9Introgression line
SA061784cbn089_b2_9Introgression line
SA061785cbn081_b1_9Introgression line
SA061786cbn080_b4_9Introgression line
SA061787cbn080_b3_9Introgression line
SA061788cbn081_b2_9Introgression line
SA061789cbn081_b3_9Introgression line
SA061790cbn089_b1_9Introgression line
SA061791cbn081_b4_9Introgression line
SA061792WN251_b2_9Introgression line
SA061793WN251_b1_9Introgression line
SA061794WN215_b1_9Introgression line
SA061795WN215_b2_9Introgression line
SA061796WN215_b3_9Introgression line
SA061797WN212_b4_9Introgression line
SA061798WN212_b3_9Introgression line
SA061799WN212_b1_9Introgression line
SA061800WN212_b2_9Introgression line
SA061801WN215_b4_9Introgression line
SA061802WN217_b1_9Introgression line
SA061803WN218_b2_9Introgression line
SA061804WN218_b3_9Introgression line
SA061805WN218_b4_9Introgression line
SA061806WN218_b1_9Introgression line
SA061807WN217_b4_9Introgression line
SA061808WN217_b2_9Introgression line
SA061809WN217_b3_9Introgression line
SA061810cbn080_b2_9Introgression line
SA061811WN251_b4_9Introgression line
SA061812cbn017_b2_9Introgression line
SA061813cbn019_b4_9Introgression line
SA061814cbn019_b3_9Introgression line
SA061815cbn019_b2_9Introgression line
SA061816cbn019_b1_9Introgression line
SA061817cbn020_b1_9Introgression line
SA061818cbn017_b1_9Introgression line
SA061819cbn020_b4_9Introgression line
SA061820cbn021_b1_9Introgression line
SA061821cbn021_b2_9Introgression line
SA061822cbn020_b2_9Introgression line
SA061823cbn080_b1_9Introgression line
SA061824cbn017_b4_9Introgression line
SA061825cbn079_b1_9Introgression line
SA061826cbn079_b2_9Introgression line
SA061827cbn079_b3_9Introgression line
SA061828cbn079_b4_9Introgression line
SA061829cbn051_b4_9Introgression line
SA061830cbn051_b3_9Introgression line
SA061831cbn017_b3_9Introgression line
SA061832cbn021_b3_9Introgression line
SA061833cbn051_b1_9Introgression line
SA061834cbn051_b2_9Introgression line
SA061835cbn020_b3_9Introgression line
SA061836CB4856_b2_8Parental strain
SA061837CB4856_b1_6Parental strain
SA061838CB4856_b1_4Parental strain
SA061839CB4856_b1_3Parental strain
SA061840CB4856_b1_8Parental strain
SA061841CB4856_b1_9Parental strain
SA061842CB4856_b3_9Parental strain
SA061843CB4856_b3_8Parental strain
SA061844CB4856_b2_9Parental strain
SA061845CB4856_b4_9Parental strain
SA061846CB4856_b1_5Parental strain
SA061847N2_b1_8Parental strain
SA061848N2_b1_6Parental strain
SA061849N2_b1_5Parental strain
SA061850N2_b1_3Parental strain
SA061851N2_b1_9Parental strain
SA061852N2_b1_4Parental strain
SA061853N2_b4_9Parental strain
SA061854N2_b3_9Parental strain
SA061855N2_b3_8Parental strain
SA061856N2_b2_8Parental strain
SA061857N2_b2_9Parental strain
SA061858WN140_b1_4RIL strain
SA061859WN137_b1_7RIL strain
SA061860WN138_b1_6RIL strain
SA061861WN139_b1_6RIL strain
SA061862WN140_b3_8RIL strain
SA061863WN137_b1_6RIL strain
SA061864WN142_b1_6RIL strain
SA061865WN141_b1_6RIL strain
SA061866WN140_b2_8RIL strain
SA061867WN140_b1_8RIL strain
SA061868WN135_b1_4RIL strain
SA061869WN134_b3_8RIL strain
SA061870WN134_b2_8RIL strain
SA061871WN134_b1_8RIL strain
SA061872WN134_b1_4RIL strain
SA061873WN142_b1_7RIL strain
SA061874WN135_b1_8RIL strain
SA061875WN136_b1_6RIL strain
SA061876WN135_b3_8RIL strain
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Collection:

Collection ID:CO001032
Collection Summary:A synchronous population of young adult worms was washed off the plates in M9 buffer and the worm pellet was washed with dH2O for three times and then collected in a 2 mL Eppendorf tube and freeze-dried overnight. Dried worm pellets were stored at room temperature until use.
Sample Type:Worms
Storage Conditions:Room temperature

Treatment:

Treatment ID:TR001052
Treatment Summary:Nematodes were cultured and maintained at 20°C on nematode growth media (NGM) agar plates. Culture conditions in all experiments were the same unless indicated otherwise. For metabolite profiling of 199 RIL strains, N2, and CB4856, age synchronized worms were obtained by alkaline hypochlorite treatment of gravid adults grown on E. coli OP50 lawn, 2000 eggs of each strain were then seeded onto NGM plates and cultured for 2.5 days allowing development to young adults.

Sample Preparation:

Sampleprep ID:SP001045
Sampleprep Summary:A synchronous population of young adult worms was washed off the plates in M9 buffer and the worm pellet was washed with dH2O for three times and then collected in a 2 mL Eppendorf tube and freeze-dried overnight. Dried worm pellets were stored at room temperature until use. A dry worm pellet was re-suspended in ice-cold 0.9% NaCl solution (250 µL). Worms were homogenized with a 5 mm steel bead using a TissueLyser II (Qiagen) for 2x2.5 min at frequency of 30 times/sec, followed by a tip sonication (energy level: 40 joule; output: 8 watts) for two times on ice water. Protein quantification was performed with BCA assay.

Combined analysis:

Analysis ID AN001628
Analysis type MS
Chromatography type Unspecified
Chromatography system Waters Acquity
Column none
MS Type ESI
MS instrument type Triple quadrupole
MS instrument name Waters Quattro Premier XE
Ion Mode NEGATIVE
Units nmol/mg of protein

Chromatography:

Chromatography ID:CH001146
Chromatography Summary:For fatty acids:The MS system consisted of an Acquity UPLC Binary Solvent manager (Waters, Milford MA) and an Acquity UPLC sample manager connected to a Quattro Premier XE mass spectrometer (Waters, Milford MA), used in the negative ESI mode. For amino acids:Liquid chromatography was performed at 50°C using a Acquity UPLC BEH C18, 1.7 µm, 2.1 x 100 mm column (Waters, Milford MA) and the injected volume was 10 µL. Mass spectrometry experiments were performed using a Micromass Quattro Premier XE Tandem Mass Spectrometer (waters, Milford, MA). The mass spectrometer was used in the multiple reaction monitoring mode (MRM) in the ESI-positive mode.
Instrument Name:Waters Acquity
Column Name:none
Chromatography Type:Unspecified

MS:

MS ID:MS001504
Analysis ID:AN001628
Instrument Name:Waters Quattro Premier XE
Instrument Type:Triple quadrupole
MS Type:ESI
Ion Mode:NEGATIVE
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