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      Significant associations of stearoyl-CoA desaturase ( SCD1) gene with fat deposition and composition in skeletal muscle

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          Abstract

          Gene expression studies in humans and animals have shown that elevated stearoyl-CoA desaturase (SCD1) activity is associated with increased fat accumulation and monounsaturation of saturated fatty acids in skeletal muscle. However, results of the two reported association studies in humans are inconsistent. In the present study, we annotated the bovine SCD1 gene and identified 3 single nucleotide polymorphisms (SNPs) in its 3'untranslated region (UTR). Genotyping these SNPs on a Wagyu x Limousin reference population revealed that the SCD1 gene was significantly associated with six fat deposition and fatty acid composition traits in skeletal muscle, but not with subcutaneous fat depth and percent kidney-pelvic-heart fat. In particular, we confirmed that the high stearoyl-CoA desaturase activities/alleles were positively correlated with beef marbling score, amount of monounsaturated fatty acids and conjugated linoleic acid content, but negatively with amount of saturated fatty acids. The inconsistent associations between human studies might be caused by using different sets of markers because we observed that most associated markers are located near the end of 3'UTR. We found that the proximity of the polyadenylation signal site is highly conserved among human, cattle and pig, indicating that the region might contain functional elements involved in posttranscriptional control of SCD1 activity. In conclusion, our cross species study provided solid evidence to support SCD1 gene as a critical player in skeletal muscle fat metabolism.

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          Most cited references 22

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          A general test of association for quantitative traits in nuclear families.

          High-resolution mapping is an important step in the identification of complex disease genes. In outbred populations, linkage disequilibrium is expected to operate over short distances and could provide a powerful fine-mapping tool. Here we build on recently developed methods for linkage-disequilibrium mapping of quantitative traits to construct a general approach that can accommodate nuclear families of any size, with or without parental information. Variance components are used to construct a test that utilizes information from all available offspring but that is not biased in the presence of linkage or familiality. A permutation test is described for situations in which maximum-likelihood estimates of the variance components are biased. Simulation studies are used to investigate power and error rates of this approach and to highlight situations in which violations of multivariate normality assumptions warrant the permutation test. The relationship between power and the level of linkage disequilibrium for this test suggests that the method is well suited to the analysis of dense maps. The relationship between power and family structure is investigated, and these results are applicable to study design in complex disease, especially for late-onset conditions for which parents are usually not available. When parental genotypes are available, power does not depend greatly on the number of offspring in each family. Power decreases when parental genotypes are not available, but the loss in power is negligible when four or more offspring per family are genotyped. Finally, it is shown that, when siblings are available, the total number of genotypes required in order to achieve comparable power is smaller if parents are not genotyped.
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            Meat fatty acid composition as affected by fatness and genetic factors: a review

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              Role of stearoyl-coenzyme A desaturase in lipid metabolism.

              Stearoyl-CoA desaturase (SCD) (EC 1.14.99.5) is an endoplasmic reticulum-bound enzyme that catalyzes the delta9-cis desaturation of saturated fatty acyl-CoAs, the preferred substrates being palmitoyl- and stearoyl-CoA, which are converted to palmitoleoyl- and oleoyl-CoA, respectively. These monounsaturated fatty acids are used as substrates for the synthesis of triglycerides, wax esters, cholesteryl esters and membrane phospholipids. The saturated to monounsaturated fatty acid ratio affects membrane phospholipid composition and alteration in this ratio has been implicated in a variety of disease states including cardiovascular disease, obesity, diabetes, neurological disease, skin disorders and cancer. Thus, the expression of SCD is of physiological importance in normal and disease states. Several mammalian SCD genes have been cloned. A single human, three mouse and two rat are the best characterized SCD genes. The physiological role of each SCD isoform and the reason for having three or more SCD gene isoforms in the rodent genome are currently unknown. A clue as to the physiological role of the SCD, at least SCD1 gene and its endogenous products came from recent studies of asebia mouse strains that have a natural mutation in the SCD1 gene and a mouse model with a targeted disruption of the SCD1 gene. In this review we discuss our current understanding of the physiological role of SCD in lipid synthesis and metabolism.
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                Author and article information

                Journal
                Int J Biol Sci
                ijbs
                International Journal of Biological Sciences
                Ivyspring International Publisher (Sydney )
                1449-2288
                2008
                25 September 2008
                : 4
                : 6
                : 345-351
                Affiliations
                1. Department of Animal Sciences, Washington State University, Pullman, WA 99164-6351, USA
                2. Department of Animal Science, University of Wyoming, Laramie, WY 82071-3684, USA
                3. USDA-ARS, Fort Keogh Livestock and Range Research Laboratory, Miles City, MT 59301, USA
                Author notes
                ✉ Correspondence to: Zhihua Jiang, Tel: +509 335 8761; Fax: +509 335 4246; E-mail: jiangz@ 123456wsu.edu

                Conflict of Interest: The authors have declared that no conflict of interest exists.

                Article
                ijbsv04p0345
                2556050
                18825276
                © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.
                Categories
                Short Research Communication

                Life sciences

                fat deposition, fatty acid composition., snps, association, scd1

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