A 680 kb duplication at the FTO locus in a kindred with obesity and a distinct body fat distribution

European Journal of Human Genetics

Volumn 21, Issue 12, 2013, Pages 1417-1422

  Davies, Robert W ^a   Lau, Paulina ^a   Naing, Thet ^a   Nikpay, Majid ^a   Doelle, Heather ^a   Ellen Harper, Mary ^b   Dent, Robert ^c   McPherson, Ruth ^a  

^a UNIVERSITY OF OTTAWA HEART INSTITUTE   (Canada)

^b UNIVERSITY OF OTTAWA   (Canada)

^c UNIVERSITY OF OTTAWA   (Canada)

Author keywords

CNV; FTO; obesity; RBL2

Indexed keywords

ADULT; AKTIP GENE; ARTICLE; BODY FAT DISTRIBUTION; BODY MASS; CHROMOSOME 16; CLINICAL FEATURE; CONTROLLED STUDY; COPY NUMBER VARIATION; DISEASE SEVERITY; EXON; FAT MASS AND OBESITY ASSOCIATED GENE; FEMALE; GENE; GENE DELETION; GENE DUPLICATION; GENE EXPRESSION; GENE LOCUS; GENE MAPPING; GENETIC ASSOCIATION; GENOTYPE; HUMAN; MAJOR CLINICAL STUDY; MALE; NECK CIRCUMFERENCE; OBESITY; PHENOTYPE; PRIORITY JOURNAL; RBL2 GENE; REAL TIME POLYMERASE CHAIN REACTION; RPGRIP1L GENE;

ADIPOSE TISSUE; ADULT; BODY MASS INDEX; DNA COPY NUMBER VARIATIONS; EUROPEAN CONTINENTAL ANCESTRY GROUP; FEMALE; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; HUMANS; MALE; MIDDLE AGED; OBESITY; POLYMORPHISM, SINGLE NUCLEOTIDE; PROTEINS;

EID: 84887621585     PISSN: 10184813     EISSN: 14765438     Source Type: Journal    
DOI: 10.1038/ejhg.2013.63     Document Type: Article

References (38)

1. Gerken T, Girard CA, Tung YC et al: The obesity-associated FTO gene encodes a 2- oxoglutarate-dependent nucleic acid demethylase. Science 2007; 318: 1469-1472.
2. Fredriksson R, Hagglund M, Olszewski PK et al: The obesity gene, FTO, is of ancient origin, up-regulated during food deprivation and expressed in neurons of feedingrelated nuclei of the brain. Endocrinology 2008; 149: 2062-2071.
3. Church C, Lee S, Bagg EA et al: A mouse model for the metabolic effects of the human fat mass and obesity associated FTO gene. PLoS Genet 2009; 5: e1000599.
4. Fischer J, Koch L, Emmerling C et al: Inactivation of the Fto gene protects from obesity. Nature 2009; 458: 894-898.
5. Frayling TM, Timpson NJ, Weedon MN et al: A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007; 316: 889-894.
6. Scuteri A, Sanna S, Chen WM et al: Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 2007; 3: e115.
7. Hinney A, Nguyen TT, Scherag A et al: Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants. PLoS ONE 2007; 2: e1361.
8. Dina C, Meyre D, Gallina S et al: Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet 2007; 39: 724-726.
9. Sallman AM, Rask-Andersen M, Jacobsson JA et al: Determination of the obesityassociated gene variants within the entire FTO gene by ultra-deep targeted sequencing in obese and lean children. Int J Obes (Lond) 2012; 37: 424-431.
10. Meyre D, Proulx K, Kawagoe-Takaki H et al: Prevalence of loss-of-function FTO mutations in lean and obese individuals. Diabetes 2010; 59: 311-318.
11. Cecil JE, Tavendale R, Watt P, Hetherington MM, Palmer CN: An obesity-associated FTO gene variant and increased energy intake in children. N Engl J Med 2008; 359: 2558-2566.
12. Berulava T, Horsthemke B: The obesity-associated SNPs in intron 1 of the FTO gene affect primary transcript levels. Eur J Hum Genet 2010; 18: 1054-1056.
13. van den BL, de Waal HD, Han JC et al: Investigation of a patient with a partial trisomy 16q including the fat mass and obesity associated gene (FTO): fine mapping and FTO gene expression study. Am J Med Genet 2010; 152A: 630-637.
14. Ahituv N, Kavaslar N, Schackwitz W et al: Medical sequencing at the extremes of human body mass. Am J Hum Genet 2007; 80: 779-791.
15. Dent R, Blackmore A, Peterson J et al: Changes in body weight and psychotropic drugs: a systematic synthesis of the literature. PLoS ONE 2012; 7: e36889.
16. Laakso M, Matilainen V, Keinanen-Kiukaanniemi S: Association of neck circumference with insulin resistance-related factors. Int J Obes Relat Metab Disord 2002; 26: 873-875.
17. Davies RW, Wells GA, Stewart AF et al: A genome-wide association study for coronary artery disease identifies a novel susceptibility locus in the major histocompatibility complex. Circ Cardiovasc Genet 2012; 5: 217-225.
18. Miller SA, Dykes DD, Polesky HF: A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215.
19. Howie BN, Donnelly P, Marchini J: A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet 2009; 5: e1000529.
20. Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D: Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 2006; 38: 904-909.
21. McCarroll SA, Kuruvilla FG, Korn JM et al: Integrated detection and population-genetic analysis of SNPs and copy number variation. Nat Genet 2008; 40: 1166-1174.
22. Wang K, Li M, Hadley D et al: PennCNV: an integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data. Genome Res 2007; 17: 1665-1674.
23. Stratigopoulos G, LeDuc CA, Cremona ML, Chung WK, Leibel RL: Cut-like homeobox 1 (CUX1) regulates expression of the fat mass and obesity-associated and retinitis pigmentosa GTPase regulator-interacting protein-1-like (RPGRIP1L) genes and coordinates leptin receptor signaling. J Biol Chem 2011; 286: 2155-2170.
24. Conrad DF, Pinto D, Redon R et al: Origins and functional impact of copy number variation in the human genome. Nature 2010; 464: 704-712.
25. Bochukova EG, Huang N, Keogh J et al: Large, rare chromosomal deletions associated with severe early-onset obesity. Nature 2010; 463: 666-670.
26. Walters RG, Jacquemont S, Valsesia A et al: A new highly penetrant form of obesity due to deletions on chromosome 16p11.2. Nature 2010; 463: 671-675.
27. Speliotes EK, Willer CJ, Berndt SI et al: Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet 2010; 42: 937-948.
28. Willer CJ, Speliotes EK, Loos RJ et al: Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 2009; 41: 25-34.
29. Jarick I, Vogel CI, Scherag S et al: Novel common copy number variation for early onset extreme obesity on chromosome 11q11 identified by a genome-wide analysis. Hum Mol Genet 2011; 20: 840-852.
30. Engelen JJ, de Die-Smulders CE, Vos PT, Meers LE, Albrechts JC, Hamers AJ: Characterization of a partial trisomy 16q with FISH. Report of a patient and review of the literature. Ann Genet 1999; 42: 101-104.
31. Grunnet LG, Nilsson E, Ling C et al: Regulation and function of FTO mRNA expression in human skeletal muscle and subcutaneous adipose tissue. Diabetes 2009; 58: 2402-2408.
32. Jowett JB, Curran JE, Johnson MP et al: Genetic variation at the FTO locus influences RBL2 gene expression. Diabetes 2010; 59: 726-732.
33. Classon M, Salama S, Gorka C, Mulloy R, Braun P, Harlow E: Combinatorial roles for pRB, p107, and p130 in E2F-mediated cell cycle control. Proc Natl Acad Sci USA 2000; 97: 10820-10825.
34. Wang Q, Li YC, Wang J et al: miR-17-92 cluster accelerates adipocyte differentiation by negatively regulating tumor-suppressor Rb2/p130. Proc Natl Acad Sci USA 2008; 105: 2889-2894.
35. Classon M, Kennedy BK, Mulloy R, Harlow E: Opposing roles of pRB and p107 in adipocyte differentiation. Proc Natl Acad Sci USA 2000; 97: 10826-10831.
36. Fox CS, Liu Y, White CC et al: Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. PLoS Genet 2012; 8: e1002695.
37. Mangge H, Renner W, Almer G, Weghuber D, Moller R, Horejsi R: Rs9939609 variant of the fat mass and obesity-associated gene and trunk obesity in adolescents. J Obes 2011; 2011: (Article ID 186368).
38. Pruim RJ, Welch RP, Sanna S et al: LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics 2010; 26: 2336-2337.