scholarly journals Identification of GLUT12/SLC2A12 as a urate transporter that regulates the blood urate level in hyperuricemia model mice

2020 ◽  
Vol 117 (31) ◽  
pp. 18175-18177
Author(s):  
Yu Toyoda ◽  
Tappei Takada ◽  
Hiroshi Miyata ◽  
Hirotaka Matsuo ◽  
Hidetoshi Kassai ◽  
...  
Keyword(s):  
Uric Acid ◽  
Physiological Function ◽  
Association Studies ◽  
Regulatory System ◽  
The Body ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Functional Assays ◽  
Urate Transporter ◽  
Genome Wide

Recent genome-wide association studies have revealed some genetic loci associated with serum uric acid levels and susceptibility to gout/hyperuricemia which contain potential candidates of physiologically important urate transporters. One of these novel loci is located upstream ofSGK1andSLC2A12, suggesting that variations in these genes increase the risks of hyperuricemia and gout. We herein focused onSLC2A12encoding a transporter, GLUT12, the physiological function of which remains unclear. As GLUT12 belongs to the same protein family as a well-recognized urate transporter GLUT9, we hypothesized that GLUT12 mediates membrane transport of urate. Therefore, we conducted functional assays and analyzedGlut12knockout hyperuricemia model mice, generated using the CRISPR-Cas9 system. Our results revealed that GLUT12 acts as a physiological urate transporter and its dysfunction elevates the blood urate concentration. This study provides insights into the deeper understanding of the urate regulatory system in the body, which is also important for pathophysiology of gout/hyperuricemia.

scholarly journals Genome-Wide Association Study of Body Fat Distribution identifies Novel Adiposity Loci and Sex-Specific Genetic Effects

2017 ◽  
Author(s):  
Mathias Rask-Andersen ◽  
Torgny Karlsson ◽  
Weronica E Ek ◽  
Åsa Johansson
Keyword(s):  
Body Fat ◽  
Genome Wide Association Study ◽  
Metabolic Diseases ◽  
Association Studies ◽  
Fat Distribution ◽  
Body Fat Distribution ◽  
The Body ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

Body mass and body fat composition are of clinical interest due to their links to cardiovascular- and metabolic diseases. Fat stored in the trunk has been suggested as more pathogenic compared to fat stored in other compartments of the body. In this study, we performed genome-wide association studies (GWAS) for the proportion of body fat distributed to the arms, legs and trunk estimated from segmental bio-electrical impedance analysis (sBIA) for 362,499 individuals from the UK Biobank. A total of 97 loci, were identified to be associated with body fat distribution, 40 of which have not previously been associated with an anthropometric trait. A high degree of sex-heterogeneity was observed and associations were primarily observed in females, particularly for distribution of fat to the legs or trunk. Our findings also implicate that body fat distribution in females involves mesenchyme derived tissues and cell types, female endocrine tissues a well as several enzymatically active members of the ADAMTS family of metalloproteinases, which are involved in extracellular matrix maintenance and remodeling.

scholarly journals Genome-Wide Association Studies for Milk Somatic Cell Score in Romanian Dairy Cattle

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1495
Author(s):  
Daniela Elena Ilie ◽  
Alexandru Eugeniu Mizeranschi ◽  
Ciprian Valentin Mihali ◽  
Radu Ionel Neamț ◽  
George Vlad Goilean ◽  
...  
Keyword(s):  
Dairy Cattle ◽  
Somatic Cell ◽  
Association Studies ◽  
Somatic Cell Score ◽  
The Body ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Cattle Breeds ◽  
Multiple Loci ◽  
Genome Wide

Mastitis is one of the most frequently encountered diseases in dairy cattle, negatively affecting animal welfare and milk production. For this reason, contributions to understanding its genomic architecture are of great interest. Genome-wide association studies (GWAS) have identified multiple loci associated with somatic cell score (SCS) and mastitis in cattle. However, most of the studies have been conducted in different parts of the world on various breeds, and none of the investigations have studied the genetic architecture of mastitis in Romanian dairy cattle breeds up to this point in time. In this study, we report the first GWAS for SCS in dairy cattle breeds from Romania. For GWAS, we used an Axiom Bovine v3 SNP-chip (>63,000 Single Nucleotide Polymorphism -SNPs) and 33,330 records from 690 cows belonging to Romanian Spotted (RS) and Romanian Brown (RB) cattle. The results found one SNP significantly associated with SCS in the RS breed and 40 suggestive SNPs with −log10 (p) from 4 to 4.9 for RS and from 4 to 5.4 in RB. From these, 14 markers were located near 12 known genes (AKAP8, CLHC1, MEGF10, SATB2, GATA6, SPATA6, COL12A1, EPS8, LUZP2, RAMAC, IL12A and ANKRD55) in RB cattle, 3 markers were close to ZDHHC19, DAPK1 and MMP7 genes, while one SNP overlapped the HERC3 gene in RS cattle. Four genes (HERC3, LUZP2, AKAP8 and MEGF10) associated with SCS in this study were previously reported in different studies. The most significant SNP (rs110749552) associated with SCS was located within the HERC3 gene. In both breeds, the SNPs and position of association signals were distinct among the three parities, denoting that mastitis is controlled by different genes that are dependent according to parity. The current results contribute to an expansion in the body of knowledge regarding the proportion of genetic variability explained by SNPs for SCS in dairy cattle.

scholarly journals Genome-Wide Association Studies for Growth Curves in Meat Rabbits Through the Single-Step Nonlinear Mixed Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Yonglan Liao ◽  
Zhicheng Wang ◽  
Leonardo S. Glória ◽  
Kai Zhang ◽  
Cuixia Zhang ◽  
...  
Keyword(s):  
Mixed Model ◽  
Growth Traits ◽  
Association Studies ◽  
Growth Curves ◽  
Single Step ◽  
The Body ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Nonlinear Mixed Model ◽  
Genome Wide

Growth is a complex trait with moderate to high heritability in livestock and must be described by the longitudinal data measured over multiple time points. Therefore, the used phenotype in genome-wide association studies (GWAS) of growth traits could be either the measures at the preselected time point or the fitted parameters of whole growth trajectory. A promising alternative approach was recently proposed that combined the fitting of growth curves and estimation of single-nucleotide polymorphism (SNP) effects into single-step nonlinear mixed model (NMM). In this study, we collected the body weights at 35, 42, 49, 56, 63, 70, and 84 days of age for 401 animals in a crossbred population of meat rabbits and compared five fitting models of growth curves (Logistic, Gompertz, Brody, Von Bertalanffy, and Richards). The logistic model was preferably selected and subjected to GWAS using the approach of single-step NMM, which was based on 87,704 genome-wide SNPs. A total of 45 significant SNPs distributed on five chromosomes were found to simultaneously affect the two growth parameters of mature weight (A) and maturity rate (K). However, no SNP was found to be independently associated with either A or K. Seven positional genes, including KCNIP4, GBA3, PPARGC1A, LDB2, SHISA3, GNA13, and FGF10, were suggested to be candidates affecting growth performances in meat rabbits. To the best of our knowledge, this is the first report of GWAS based on single-step NMM for longitudinal traits in rabbits, which also revealed the genetic architecture of growth traits that are helpful in implementing genome selection.

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