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      Identification of gene variation within porcine PRDM16 gene and its association with fat and loin muscle area

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          Abstract

          The PR domain containing the 16 (PRDM16) gene, also known as the MDS1/EVI1-like gene (MEL1), may act as a bidirectional switch between brown fat and skeletal muscle in mice. The molecular characteristics and possible biological function of porcine PRDM16 gene have been less reported. In this study, the mRNA expression profile, linkage mapping and association analyses of the PRDM16 gene were carried out in the pig. The PRDM16 mRNA was expressed widely in various tissues including fat and the longissimus dorsi muscle. One SNP c.-3284+171C>T in intron 14 was identified and that made the PRDM16 gene being assigned between SWR1130 and SW122 on SSC6. The different genotypes of c.-3284+171C>T were significantly associated with backfat and loin muscle area in the ISU Berkshire × Yorkshire pig resource family, but such associations were not verified in another pig population. The discovery of additional mutations and association studies are warranted before the PRDM16 gene can be recommended for marker assisted selection in the pig.

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          Transcriptional control of brown fat determination by PRDM16.

          Brown fat cells are specialized to dissipate energy and can counteract obesity; however, the transcriptional basis of their determination is largely unknown. We show here that the zinc-finger protein PRDM16 is highly enriched in brown fat cells compared to white fat cells. When expressed in white fat cell progenitors, PRDM16 activates a robust brown fat phenotype including induction of PGC-1alpha, UCP1, and type 2 deiodinase (Dio2) expression and a remarkable increase in uncoupled respiration. Transgenic expression of PRDM16 at physiological levels in white fat depots stimulates the formation of brown fat cells. Depletion of PRDM16 through shRNA expression in brown fat cells causes a near total loss of the brown characteristics. PRDM16 activates brown fat cell identity at least in part by simultaneously activating PGC-1alpha and PGC-1beta through direct protein binding. These data indicate that PRDM16 can control the determination of brown fat fate.
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            Genome-wide array comparative genomic hybridization analysis reveals distinct amplifications in osteosarcoma

            Background Osteosarcoma is a highly malignant bone neoplasm of children and young adults. It is characterized by extremely complex karyotypes and high frequency of chromosomal amplifications. Currently, only the histological response (degree of necrosis) to therapy represent gold standard for predicting the outcome in a patient with non-metastatic osteosarcoma at the time of definitive surgery. Patients with lower degree of necrosis have a higher risk of relapse and poor outcome even after chemotherapy and complete resection of the primary tumor. Therefore, a better understanding of the underlying molecular genetic events leading to tumor initiation and progression could result in the identification of potential diagnostic and therapeutic targets. Methods We used a genome-wide screening method – array based comparative genomic hybridization (array-CGH) to identify DNA copy number changes in 48 patients with osteosarcoma. We applied fluorescence in situ hybridization (FISH) to validate some of amplified clones in this study. Results Clones showing gains (79%) were more frequent than losses (66%). High-level amplifications and homozygous deletions constitute 28.6% and 3.8% of tumor genome respectively. High-level amplifications were present in 238 clones, of which about 37% of them showed recurrent amplification. Most frequently amplified clones were mapped to 1p36.32 (PRDM16), 6p21.1 (CDC5L, HSPCB, NFKBIE), 8q24, 12q14.3 (IFNG), 16p13 (MGRN1), and 17p11.2 (PMP22 MYCD, SOX1,ELAC27). We validated some of the amplified clones by FISH from 6p12-p21, 8q23-q24, and 17p11.2 amplicons. Homozygous deletions were noted for 32 clones and only 7 clones showed in more than one case. These 7 clones were mapped to 1q25.1 (4 cases), 3p14.1 (4 cases), 13q12.2 (2 cases), 4p15.1 (2 cases), 6q12 (2 cases), 6q12 (2 cases) and 6q16.3 (2 cases). Conclusions This study clearly demonstrates the utility of array CGH in defining high-resolution DNA copy number changes and refining amplifications. The resolution of array CGH technology combined with human genome database suggested the possible target genes present in the gained or lost clones.
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              A molecular genome scan analysis to identify chromosomal regions influencing economic traits in the pig. I. Growth and body composition.

              Genome scans can be employed to identify chromosomal regions and eventually genes (quantitative trait loci or QTL) that control quantitative traits of economic importance. A three-generation resource family was developed by using two Berkshire grand sires and nine Yorkshire grand dams to detect QTL for growth and body composition traits in pigs. A total of 525 F2 progeny were produced from 65 matings. All F2 animals were phenotyped for birth weight, 16-day weight, growth rate, carcass weight, carcass length, back fat thickness, and loin eye area. Animals were genotyped for 125 microsatellite markers covering the genome. Least squares regression interval mapping was used for QTL detection. All carcass traits were adjusted for live weight at slaughter. A total of 16 significant QTL, as determined by a permutation test, were detected at the 5% chromosome-wise level for growth traits on Chromosomes (Chrs) 1, 2, 3, 4, 6, 7, 8, 9, 11, 13, 14, and X, of which two were significant at the 5% genome-wise level and two at the 1% genome-wise level (on Chrs 1, 2, and 4). For composition traits, 20 QTL were significant at the 5% chromosome-wise level (on Chrs 1, 4, 5, 6, 7, 12, 13, 14, 18), of which one was significant at the 5% genome-wise level and three were significant at the 1% genome-wise level (on Chrs 1, 5, and 7). For several QTL the favorable allele originated from the breed with the lower trait mean.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Journal
                sajas
                South African Journal of Animal Science
                S. Afr. j. anim. sci.
                The South African Society for Animal Science (SASAS) (Pretoria )
                2221-4062
                2009
                : 39
                : 4
                : 333-336
                Affiliations
                [1 ] Huazhong Agricultural University Peoples R China
                [2 ] Iowa State University USA
                Article
                S0375-15892009000400012
                fc2c8d86-7f5d-4d5e-94d7-257007d6ea26

                http://creativecommons.org/licenses/by/4.0/

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                Product

                SciELO South Africa

                Self URI (journal page): http://www.scielo.org.za/scielo.php?script=sci_serial&pid=0375-1589&lng=en
                Categories
                Agriculture, Dairy & Animal Science
                Genetics & Heredity
                Nutrition & Dietetics
                Physiology

                Animal agriculture,Nutrition & Dietetics,Anatomy & Physiology,Genetics
                PRDM16,linkage mapping,association analysis,backfat,loin muscle area

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