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- Deng, Min, et al.
(författare)
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Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis
- 2013
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 45:6, s. 697-
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, P-combined = 2.92 x 10(-8), odds ratio (OR) = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, P-combined = 2.35 x 10(-9), OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.
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| 2. |
- Wang, Dandan, et al.
(författare)
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Porcine ZBED6 regulates growth of skeletal muscle and internal organs via multiple targets
- 2021
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 17:10
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Tidskriftsartikel (refereegranskat)abstract
- ZBED6 (zinc finger BED domain containing protein 6) is a transcription factor unique to placental mammals and its interaction with the IGF2 (insulin-like growth factor 2) locus plays a prominent role in the regulation of postnatal skeletal muscle growth. Here, we generated lean Bama miniature pigs by generating ZBED6-knockout (ZBED6(-/-)) and investigated the mechanism underlying ZBED6 in growth of muscle and internal organs of placental mammals. ZBED6(-/-) pigs show markedly higher lean mass, lean mass rate, larger muscle fiber area and heavier internal organs (heart and liver) than wild-type (WT) pigs. The striking phenotypic changes of ZBED6(-/-) pigs coincided with remarkable upregulation of IGF2 mRNA and protein expression across three tissues (gastrocnemius muscle, longissimus dorsi, heart). Despite a significant increase in liver weight, ZBED6(-/-) pigs show comparable levels of IGF2 expression to those of WT controls. A mechanistic study revealed that elevated methylation in the liver abrogates ZBED6 binding at the IGF2 locus, explaining the unaltered hepatic IGF2 expression in ZBED6(-/-) pigs. These results indicate that a ZBED6-IGF2-independent regulatory pathway exists in the liver. Transcriptome analysis and ChIP-PCR revealed new ZBED6 target genes other than IGF2, including cyclin dependent kinase inhibitor 1A (CDKN1A) and tsukushi, small leucine rich proteoglycan (TSKU), that regulates growth of muscle and liver, respectively. Author summary The lean meat rate is an important economic trait for the swine industry and it is determined by muscle growth and development. A single base change in intron 3 of the insulin-like growth factor 2 (IGF2) gene increases meat production in pigs by disrupting a binding site for zinc finger BED domain containing protein 6 (ZBED6). Chinese indigenous pig breeds carrying the homozygous IGF2 wild-type allele produce low lean meat. We thus generate a lean pig model in Chinese Bama pig by knocking out ZBED6. In this model, we demonstrate that ZBED6 KO increases muscle and internal organ growth through ZBED6-IGF2 axis and other target genes. These results not only open new strategies for lean meat breeding in Chinese indigenous pigs, but also provide new insights to the global function of ZBED6 in organ growth and development.
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| 4. |
- Xie, Rongrong, et al.
(författare)
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Salt intrusion alters nitrogen cycling in tidal reaches as determined in field and laboratory investigations
- 2020
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 729
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Tidskriftsartikel (refereegranskat)abstract
- Salinization is a growing problem throughout the world and poses a threat especially to freshwater ecosystems. However, much remains to be learned about the mechanisms by which salinity impacts microbially mediated biogeochemical processes. Elevated nitrogen (N) concentrations in estuarine ecosystems have led to their eutrophication, but the relationship between N transformation and the functional genes involved in the response to saltwater intrusion is poorly understood. Here, using the Minjiang River, a tidal river in southeastern China as an easily accessible natural laboratory, we conducted a 2-year field survey to investigate N speciation during ebb and flood tides. Then, in a laboratory experiment we simulated the varying degrees of salt intrusion that occur in natural tidal reaches. The microcosm study allowed quantitative assessments of N transformation and functional gene responses. The field surveys showed that concentrations of NH4+ rose during flood tides, while the concentrations of NO3- and total N fluctuated. In the microcosms, NO3- concentrations decreased in response to salt pulses, due to simultaneous declines in the abundance of genes responsible for nitrification and increases in the abundance of those involved in dissimilatory nitrate reduction to ammonium (DNRA). The elevated salinity led to increased yields of NH4+, a response that correlated positively with the abundance of nrfA genes, involved in DNRA. Furthermore, an increase in salinity promoted N2O accumulation during the denitrification process. Altogether, our study suggests that saltwater intrusion leads to a decrease in nitrification while favoring N transformation via denitrification and DNRA and that N2O accumulation in the water is dependent on the strength of the salt pulse.
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