Dataset Information

Genetic Fine-Mapping and Identification of Candidate Genes and Variants for Adiposity Traits in Outbred Rats.

ABSTRACT: OBJECTIVE:Obesity is a major risk factor for multiple diseases and is in part heritable, yet the majority of causative genetic variants that drive excessive adiposity remain unknown. Here, outbred heterogeneous stock (HS) rats were used in controlled environmental conditions to fine-map novel genetic modifiers of adiposity. METHODS:Body weight and visceral fat pad weights were measured in male HS rats that were also genotyped genome-wide. Quantitative trait loci (QTL) were identified by genome-wide association of imputed single-nucleotide polymorphism (SNP) genotypes using a linear mixed effect model that accounts for unequal relatedness between the HS rats. Candidate genes were assessed by protein modeling and mediation analysis of expression for coding and noncoding variants, respectively. RESULTS:HS rats exhibited large variation in adiposity traits, which were highly heritable and correlated with metabolic health. Fine-mapping of fat pad weight and body weight revealed three QTL and prioritized five candidate genes. Fat pad weight was associated with missense SNPs in Adcy3 and Prlhr and altered expression of Krtcap3 and Slc30a3, whereas Grid2 was identified as a candidate within the body weight locus. CONCLUSIONS:These data demonstrate the power of HS rats for identification of known and novel heritable mediators of obesity traits.

SUBMITTER: Keele GR

PROVIDER: S-EPMC5740008 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic Fine-Mapping and Identification of Candidate Genes and Variants for Adiposity Traits in Outbred Rats.

Keele Gregory R GR Prokop Jeremy W JW He Hong H Holl Katie K Littrell John J Deal Aaron A Francic Sanja S Cui Leilei L Gatti Daniel M DM Broman Karl W KW Tschannen Michael M Tsaih Shirng-Wern SW Zagloul Maie M Kim Yunjung Y Baur Brittany B Fox Joseph J Robinson Melanie M Levy Shawn S Flister Michael J MJ Mott Richard R Valdar William W Solberg Woods Leah C LC

Obesity (Silver Spring, Md.) 20171128 1

<h4>Objective</h4>Obesity is a major risk factor for multiple diseases and is in part heritable, yet the majority of causative genetic variants that drive excessive adiposity remain unknown. Here, outbred heterogeneous stock (HS) rats were used in controlled environmental conditions to fine-map novel genetic modifiers of adiposity.<h4>Methods</h4>Body weight and visceral fat pad weights were measured in male HS rats that were also genotyped genome-wide. Quantitative trait loci (QTL) were identif ...[more]

PMID: 29193816

Similar Datasets

Project description:Seed coat color is a typical morphological trait that can be used to reveal the evolution of soybean. The study of seed coat color-related traits in soybeans is of great significance for both evolutionary theory and breeding practices. In this study, 180 F10 recombinant inbred lines (RILs) derived from the cross between the yellow-seed coat cultivar Jidou12 (ZDD23040, JD12) and the wild black-seed coat accession Y9 (ZYD02739) were used as materials. Three methods, single-marker analysis (SMA), interval mapping (IM), and inclusive composite interval mapping (ICIM), were used to identify quantitative trait loci (QTLs) controlling seed coat color and seed hilum color. Simultaneously, two genome-wide association study (GWAS) models, the generalized linear model (GLM) and mixed linear model (MLM), were used to jointly identify seed coat color and seed hilum color QTLs in 250 natural populations. By integrating the results from QTL mapping and GWAS analysis, we identified two stable QTLs (qSCC02 and qSCC08) associated with seed coat color and one stable QTL (qSHC08) related to seed hilum color. By combining the results of linkage analysis and association analysis, two stable QTLs (qSCC02, qSCC08) for seed coat color and one stable QTL (qSHC08) for seed hilum color were identified. Upon further investigation using Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we validated the previous findings that two candidate genes (CHS3C and CHS4A) reside within the qSCC08 region and identified a new QTL, qSCC02. There were a total of 28 candidate genes in the interval, among which Glyma.02G024600, Glyma.02G024700, and Glyma.02G024800 were mapped to the glutathione metabolic pathway, which is related to the transport or accumulation of anthocyanin. We considered the three genes as potential candidate genes for soybean seed coat-related traits. The QTLs and candidate genes detected in this study provide a foundation for further understanding the genetic mechanisms underlying soybean seed coat color and seed hilum color and are of significant value in marker-assisted breeding.

Dataset Information

Genetic Fine-Mapping and Identification of Candidate Genes and Variants for Adiposity Traits in Outbred Rats.

Publications

Genetic Fine-Mapping and Identification of Candidate Genes and Variants for Adiposity Traits in Outbred Rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets