RAR-related orphan receptor A isoform 1 (RORa1) is disrupted by a balanced translocation t(4;15)(q22.3;q21.3) associated with severe obesity

European Journal of Human Genetics

Volumn 13, Issue 8, 2005, Pages 928-934

  Klar, Joakim ^a   Åsling, Bengt ^b   Carlsson, Birgit ^a   Ulvsbäck, Magnus ^b   Dellsén, Anita ^b   Ström, Carina ^b   Rhedin, Magdalena ^b   Forslund, Anders ^c   Annerén, Göran ^a   Ludvigsson, Jonas F ^d   Dahl, Niklas ^a  

^a UPPSALA UNIVERSITY   (Sweden)

^b ASTRAZENECA R AND D   (Sweden)

^c UPPSALA UNIVERSITY   (Sweden)

^d ÖREBRO UNIVERSITY   (Sweden)

Author keywords

Obesity; RORa; Translocation

Indexed keywords

CELL NUCLEUS RECEPTOR; ISOPROTEIN; LIPOPROTEIN; PYRUVATE DEHYDROGENASE;

ADIPOCYTE; ADOLESCENT; ADULT; ARTICLE; BODY MASS; CASE REPORT; CELLULAR DISTRIBUTION; CHROMOSOME ANALYSIS; CHROMOSOME REARRANGEMENT; CHROMOSOME TRANSLOCATION 15; CHROMOSOME TRANSLOCATION 4; DISEASE SEVERITY; EXON; FAMILIAL DISEASE; FEMALE; FUSION GENE; GENE DELETION; GENE DISRUPTION; GENE MAPPING; GENE SEQUENCE; GENETIC TRANSCRIPTION AND TRANSLATION; HETEROZYGOTE; HUMAN; HUMAN CELL; HUMAN TISSUE; HYPOTHESIS; LABORATORY TEST; LIPOPROTEIN METABOLISM; MALE; MOLECULAR CLONING; OBESITY; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; REGULATORY MECHANISM; SEQUENCE ANALYSIS;

ADIPOCYTES; ADOLESCENT; ADULT; BASE SEQUENCE; BLOTTING, WESTERN; CELLS, CULTURED; CHROMOSOME BREAKAGE; CHROMOSOME MAPPING; CHROMOSOMES, HUMAN, PAIR 15; CHROMOSOMES, HUMAN, PAIR 4; FEMALE; HUMANS; KARYOTYPING; MALE; MOTHERS; OBESITY, MORBID; PHENOTYPE; RECEPTOR PROTEIN-TYROSINE KINASES; RECEPTORS, CELL SURFACE; TRANSLOCATION, GENETIC;

EID: 23644448601     PISSN: 10184813     EISSN: None     Source Type: Journal    
DOI: 10.1038/sj.ejhg.5201433     Document Type: Article

References (36)

1. Leibel RL, Chung WK, Chua Jr SC: The molecular genetics of rodent single gene obesities. J Biol Chem 1997; 272: 31937-31940.
2. Chagnon YC, Rankinen T, Snyder EE, Weisnagel SJ, Perusse L, Bouchard C: The human obesity gene map: the 2002 update. Obes Res 2003; 11: 313-367.
3. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM: Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 425-432.
4. Tartaglia LA, Dembski M, Weng X et al: Identification and expression cloning of a leptin receptor, OB-R. Cell 1995; 83: 1263-1271.
5. Clement K, Vaisse C, Lahlou N et al: A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 1998; 392: 398-401.
6. Montague CT, Farooqi IS, Whitehead JP et al: Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997; 387: 903-908.
7. Cheung CC, Clifton DK, Steiner RA: Proopiomelanocortin neurons are direct targets for leptin in the hypothalamus. Endocrinology 1997; 138: 4489-4492.
8. Yaswen L, Diehl N, Brennan MB, Hochgeschwender U: Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin. Nat Med 1999; 5: 1066-1070.
9. Jackson RS, Creemers JW, Ohagi S et al: Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet 1997; 16: 303-306.
10. Krude H, Biebermann H, Luck W, Horn R, Brabant G, Gruters A: Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet 1998; 19: 155-157.
11. Lee YS, Poh LK, Loke KY: A novel melanocortin 3 receptor gene (MC3R) mutation associated with severe obesity. J Clin Endocrinol Metab 2002; 87: 1423-1426.
12. Vaisse C, Clement K, Guy-Grand B, Froguel P: A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat Genet 1998; 20: 113-114.
13. Yeo GS, Farooqi IS, Aminian S, Halsall DJ, Stanhope RG, O'Rahilly S: A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat Genet 1998; 20: 111-112.
14. Cummings DE, Schwartz MW: Melanocortins and body weight: a tale of two receptors. Nat Genet 2000; 26: 8-9.
15. Holder Jr JL, Butte NF, Zinn AR: Profound obesity associated with a balanced translocation that disrupts the SIM1 gene. Hum Mol Genet 2000; 9: 101-108.
16. Michaud JL, Boucher F, Melnyk A et al: Sim1 haploinsufficiency causes hyperphagia, obesity and reduction of the paraventricular nucleus of the hypothalamus. Hum Mol Genet 2001; 10: 1465-1473.
17. Gallagher D, Heymsfield SB, Heo M, Jebb SA, Murgatroyd PR, Sakamoto Y: Healthy percentage body fat ranges: an approach for developing guidelines based on body mass index. Am J Clin Nutr 2000; 72: 694-701.
18. Dib C, Faure S, Fizames C et al: A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature 1996; 380: 152-154.
19. Schwartz S, Zhang Z, Frazer KA et al: PipMaker - a web server for aligning two genomic DNA sequences. Genome Res 2000; 10: 577-586.
20. Abeysinghe SS, Chuzhanova N, Krawczak M, Ball EV, Cooper DN: Translocation and gross deletion breakpoints in human inherited disease and cancer I: nucleotide composition and recombination-associated motifs. Hum Mutat 2003; 22: 229-244.
21. Chuzhanova N, Abeysinghe SS, Krawczak M, Cooper DN: Translocation and gross deletion breakpoints in human inherited disease and cancer II: potential involvement of repetitive sequence elements in secondary structure formation between DNA ends. Hum Mutat 2003; 22: 245-251.
22. Giguere V, McBroom L, Flock G: Determinants of target gene specificity for ROR alpha 1: monomeric DNA binding by an orphan nuclear receptor. Mol Cell Biol 1995; 15: 2517-2526.
23. Vu-Dac N, Gervois P, Grotzinger T et al: Transcriptional regulation of apolipoprotein A-I gene expression by the nuclear receptor RORalpha. J Biol Chem 1997; 272: 22401-22404.
24. Delerive P, Chin WW, Suen CS: Identification of Reverb(alpha) as a novel ROR(alpha) target gene. J Biol Chem 2002; 277: 35013-35018.
25. Zannis VI, Kan HY, Kritis A, Zanni EE, Kardassis D: Transcriptional regulatory mechanisms of the human apolipoprotein genes in vitro and in vivo. Curr Opin Lipidol 2001; 12: 181-207.
26. Lau P, Nixon SJ, Parton RG, Muscat GE: RORalpha regulates the expression of genes involved in lipid homeostasis in skeletal muscle cells: caveolin-3 and CPT-1 are direct targets of ROR. J Biol Chem 2004; 279: 36828-36840.
27. Sundvold H, Lien S: Identification of a novel peroxisome proliferator-activated receptor (PPAR) gamma promoter in man and transactivation by the nuclear receptor RORalpha1. Biochem Biophys Res Commun 2001; 287: 383-390.
28. Fryns JP, de Muelenaere A, van den Berghe H: Interstitial deletion of the long arm of chromosome 15. Ann Genet 1982; 25: 59-60.
29. Martin F, Platt J, Tawn E, Burn J: A de novo interstitial deletion of 15(g21.2q22.1) in a moderately retarded adult male. J Med Genet 1990; 27: 637-639.
30. Yip MY, Selikowitz M, Don N, Kovacic A, Purvis-Smith S, Lam-Po-Tang PR: Deletion 15g21.1-q22.1 resulting from a paternal insertion into chromosome 5. J Med Genet 1987; 24: 709-712.
31. Liehr T, Starke H, Heller A et al: Evidence for a new microdeletion syndrome in 15q21. Int J Mol Med 2003; 11: 575-577.
32. Thiebault K, Mazelin L, Pays L et al: The netrin-1 receptors UNC5 H are putative tumor suppressors controlling cell death commitment. Proc Natl Acad Sci USA 2003; 100: 4173-4178.
33. Choi YS, Hong SB, Jeon HK et al: Insertional mutation in the intron 1 of Unc5h3 gene induces ataxic, lean and hyperactive phenotype in mice. Exp Anim 2003; 52: 273-283.
34. Matysiak-Scholze U, Nehls M: The structural integrity of ROR alpha isoforms is mutated in staggerer mice: cerebellar coexpression of ROR alpha1 and ROR alpha4. Genomics 1997; 43: 78-84.
35. Kleinjan DJ, van Heyningen V: Position effect in human genetic disease. Hum Mol Genet 1998; 7: 1611-1618.
36. Gabrielsson BL, Carlsson B, Carlsson LM: Partial genome scale analysis of gene expression in human adipose tissue using DNA array. Obes Res 2000; 8: 374-384.