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US 20070021589A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2007/0021589 A1 Collier et al. (43) Pub. Date: Jan. 25, 2007 (54) OBESITY-RELATED GENES (52) U.S. Cl. .......................... 530/350; 514/12: 435/69.1; (76) Inventors: Greg Collier, Ocean Grove (AU); Ken 435/320.1; 435/325; 536/23.5 Walder, Ocean Grove (AU); David Segal, Ocean Grove (AU); Victoria C. Foletta, Ocean Grove (AU) (57) ABSTRACT Correspondence Address: SCULLY, SCOTT, MURPHY & PRESSER The present invention relates generally to a nucleic acid 4OO GARDEN CITY PLAZA molecule which is expressed in at least red gastrocnemius SUTE 3OO muscle or its equivalent under particular physiological con GARDEN CITY, NY 11530 (US) ditions. It is proposed that the nucleic acid molecule is (21) Appl. No.: 10/541,998 differentially expressed under differing conditions of healthy state, myopathy, obesity, anorexia, weight maintenance, (22) PCT Filed: Jan. 13, 2004 diabetes, disorders associated with mitochondrial dysfunc (86). PCT No.: PCT/AUO4/OOO43 tion, genetic disorders, cancer, heart disease, inflammation, S 371(c)(1), disorders associated with the immune system, infertility, (2), (4) Date: Jan. 17, 2006 disease associated with the brain and/or metabolic energy levels. The subject nucleic acid molecule and/or its expres (30) Foreign Application Priority Data sion product is proposed to be used in therapeutic and diagnostic protocols for conditions such as healthy state, Jan. 13, 2003 (US)........................................... 60439767 myopathy, obesity, anorexia, weight maintenance, diabetes, Publication Classification disorders associated with mitochondrial dysfunction, (51) Int. Cl. genetic disorders, cancer, heart disease, inflammation, dis C07K I4/705 (2007.01) orders associated with the immune system, infertility, dis A6 IK 38/17 (2007.01) ease associated with the brain and/or metabolic energy C7H 2L/04 (2006.01) levels or as targets for the design and/or identification of CI2P 2/06 (2006.01) modulators of their activity and/or function. US 2007/0021589 A1 Jan. 25, 2007 OBESTY-RELATED GENES 0008. In Australia, the recent AusLiab study estimated that 7.5 million Australians (60%) aged 25 years and over BACKGROUND OF THE INVENTION were overweight or obese. Of these, 2.6 million (21%) were obese (BMI>30) (Dunstan et al., Diabetes Res. Clin. Pract. 0001) 1. Field of the Invention 57: 119-129, 2002). Similarly, the prevalence of obesity in 0002 The present invention relates generally to a nucleic the U.S. increased substantially between 1991 and 1998, acid molecule which is expressed in at least red gastrocne increasing from 12% to 18% in Americans during this period mius muscle or its equivalent under particular physiological (Mokdad et al., JAMA 282(16): 1519-1522, 1999). conditions. It is proposed that the nucleic acid molecule is 0009. The high and increasing prevalence of obesity has differentially expressed under differing conditions of healthy serious health implications for both individuals and society state, myopathy, obesity, anorexia, weight maintenance, as a whole. Obesity is a complex and heterogeneous disorder diabetes, disorders associated with mitochondrial dysfunc and has been identified as a key risk indicator of preventable tion, genetic disorders, cancer, heart disease, inflammation, morbidity and mortality as obesity increases the risk of a disorders associated with the immune system, infertility, number of other metabolic conditions including type 2 disease associated with the brain and/or metabolic energy diabetes mellitus and cardiovascular disease (Must et al., levels. The subject nucleic acid molecule and/or its expres JAMA 282(16): 1523-1529, 1999: Kopelman, Nature 404: sion product is proposed to be used in therapeutic and 635-643, 2000). Alongside obesity the prevalence of diabe diagnostic protocols for conditions such as healthy state, tes continues to increase rapidly. The AusLiab Survey esti myopathy, obesity, anorexia, weight maintenance, diabetes, mated that close to 1 million Australians aged 25 years and disorders associated with mitochondrial dysfunction, over have type 2 diabetes (Dunstan et al., 2002). This genetic disorders, cancer, heart disease, inflammation, dis represents approximately 7.5% of the population. In the orders associated with the immune system, infertility, dis U.S., the number of adults with diabetes increased by 49% ease associated with the brain and/or metabolic energy between 1991 and 2000 (Marx, Science 686-689, 2002). It levels or as targets for the design and/or identification of has been estimated that about 17 million people in the U.S. modulators of their activity and/or function. have type 2 diabetes and an equal number are thought to be pre-diabetic (Marx, 2002). In Australia, the annual costs of 0003 2. Description of the Prior Art obesity associated with diabetes and other disease conditions 0004 Bibliographic details of references provided in the has been conservatively estimated to be AUS$810 million subject specification are listed at the end of the specification. for 1992-93 (National Health and Medical Research Coun cil, Acting on Australia's weight. A strategy for the preven 0005 Reference to any prior art in this specification is tion of overweight and obesity. Canberra: National Health not, and should not be taken as, an acknowledgment or any and Medical Research Council, 1996). The direct costs of form of Suggestion that this prior art forms part of the diabetes and its complications in Australia in 1993-94 were common general knowledge in any country. estimated at S681 million, or 2.2% of total health system 0006 The increasing sophistication of recombinant DNA costs in that year (Australian Institute of Health and Welfare technology is greatly facilitating research and development (AIWH), Australia's Health, 2002, Canberra: AIWH). in the medical, veterinary and allied human and animal 0010. A genetic basis for the etiology of obesity is health fields. This is particularly the case in the investigation indicated inter alia from Studies in twins, adoption studies of the genetic bases involved in the etiology of certain and population-based analyses which suggest that genetic disease conditions. One particularly significant condition effects account for 25-80% of the variation in body weight from the stand point of morbidity and mortality is obesity in the general population (Bouchard, 1994, Supra; Kopelman and its association with type 2 diabetes (formerly non et al., Int. J. Obesity 18: 188-191, 1994; Ravussin, Metabo insulin-dependent diabetes mellitus or NIDDM) and cardio lism 44(3): 12-14, 1995). It is considered that genes deter vascular disease. mine the possible range of body weight in an individual and then the environment influences the point within this range 0007 Obesity is defined as a pathological excess of body where the individual is located at any given time (Bouchard, fat and is the result of an imbalance between energy intake 1994). However, despite numerous studies into genes and energy expenditure for a Sustained period of time. thought to be involved in the pathogenesis of obesity, there Obesity is the most common metabolic disease found in affluent societies. The prevalence of obesity in these nations have been Surprisingly few significant findings in this area. is alarmingly high, ranging from 10% to upwards of 50% in In addition, genome-wide scans in various population Some Sub-populations (Bouchard. The genetics of Obesity, groups have not produced definitive evidence of the chro Boca Raton: CRC Press, 1994). Of particular concern is the mosomal regions having a major effect on obesity. fact that the prevalence of obesity appears to be rising 0011) A number of tissues have been implicated in the consistently in affluent Societies and is now increasing pathophysiology of obesity and type 2 diabetes, and of rapidly in less prosperous nations as they become more particular interest is the muscle. Skeletal muscle is the affluent and/or adopt cultural practices similar to those in principle site of insulin-stimulated glucose disposal, more affluent countries (Zimmet, Diabetes Care 15: 232 accounting for approximately 75% of total glucose uptake. 252, 1992). The escalating rates of obesity globally have Skeletal muscle is also the major site of peripheral insulin resulted in the World Health Organisation declaring an resistance. Skeletal muscle also oxidizes free fatty acids for obesity epidemic worldwide (World Trade Organisation. fuel, to meet its energy requirements. In healthy individuals, Obesity. Preventing and managing the global epidemic. the muscle has the capacity to utilize both carbohydrate and Report of a WHO Consultation on Obesity. Geneva: World lipids for energy and to fluctuate between these fuels in Health Organisation, 1998). response to a range of signals including insulin concentra US 2007/0021589 A1 Jan. 25, 2007 tions. This metabolic flexibility is central to the role the both known genes and unknown transcripts. Using cDNA muscle plays in whole body fuel metabolism and with microarrays, comparative estimates can be obtained of the diseases such as obesity and type 2 diabetes, this flexibility level of gene expression of large numbers of genes (up to may be lost. 20,000 per microarray) in each sample. cDNA microarrays generally involve a large number of DNA “spots” in an SUMMARY OF THE INVENTION orderly array chemically coupled to the surface of a solid Substrate, usually but not exclusively an optically flat glass 0012 Throughout this specification, unless the context microscope slide. Fluorescently labeled cDNAs are gener requires otherwise, the word “comprise', or variations such ated from experimental and reference RNA samples and as “comprises” or “comprising, will be understood to imply then competitively hybridized to the gene chip. The experi the inclusion of a stated element or integer or group of mental and reference cDNAs are labeled with a different elements or integers but not the exclusion of any other fluorescent dye and the intensity of each fluor at each DNA element or integer or group of elements or integers.
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