Human elongase genes and uses thereof

• US 20040086899A1
• Filed: 11/20/2003
• Published: 05/06/2004
• Est. Priority Date: 11/29/2000
• Status: Active Grant

• Current Assignee: Quantanova Canada, Ltd., Xenon Pharmaceuticals Inc.
• Original Assignee: Xenon Pharmaceuticals Inc.
• Inventors: Ponton, Andre, Knickle, Leah Christine, Goldberg, Y Paul, Jenkins, D Kenneth, Nwaka, Solomon O, Haardt, Martin, Winther, Michael David, De Antueno, Roberto Justo, Allen, Stephen John
• Granted Patent: US 7,297,523 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/32 Alcohol-abuse
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C12N 9/1029 : transferring groups other than amino-acyl groups (2.3.1)

Abstract

The present invention relates to elongase genes, their polypeptides and their control regions, and the use of such genes, polypeptides and control regions in determining compositions for use in the treatment of disease. The identified compositions regulate the expression of the elongase genes or modulate the activity of their protein products. The nucleotide and amino acid sequences are taught for ELG4, ELG6 and ELG7. The control sequences and function are taught for ELG1, ELG2, ELG3, ELG4, ELG5, ELG6 and ELG7.

Claims

1. An isolated polynucleotide sequence, comprising a polynucleotide sequence which is selected from the group consisting of:

(a) a sequence comprising SEQ ID NO;

4;

(b) a sequence comprising SEQ ID NO;

8;

(c) a sequence comprising SEQ ID NO;

11;

(d) a sequence which is at least 80% homologous with a sequence of any of (a) to (c);

(e) a sequence which is at least 90% homologous with a sequence of any of (a) to (c);

(f) a sequence which is at least 95% homologous with a sequence of any of (a) to (c);

(g) a sequence which is at least 98% homologous with a sequence of any of (a) to (c);

(h) a sequence which is at least 99% homologous with a sequence of any of (a) to (c); and

;

(i) a sequence which hybridizes to any of (a) to (h) under stringent conditions.

2. An isolated polynucleotide sequence of claim 1, wherein the isolated polynucleotide sequence is cDNA.

3. A vector comprising a polynucleotide sequence of claim 1 in a suitable vector.

4. A host cell comprising a polynucleotide sequence of claim 1 in a host cell which is heterologous to said sequence.

5. An isolated polynucleotide fragment selected from the group consisting of:

(a) a sequence having at least 15 sequential bases of nucleotides of a sequence of claim 1;

(b) a sequence having at least 30 sequential bases of nucleotides of a sequence of claim 1;

and

(c) a sequence having at least 50 sequential bases of nucleotides of a sequence of claim 1.

6. A vector comprising a polynucleotide sequence of claim 5 contained in a vector which is heterologous to said sequence.

7. A vector of claims 3 or 6, wherein said vector contains or encodes a tag.

8. An isolated polynucleotide sequence, comprising a polynucleotide sequence which retains substantially the same biological fimction or activity as or is a functional derivative of a polynucleotide of claim 1.

9. A method for identifying a compound which inhibits or promotes the activity of a polynucleotide sequence of claim 1, comprising the steps of:

(a) selecting a control animal having said sequence and a test animal having said sequence;

(b) treating said test animal using a compound; and

,

(c) determining the relative quantity of an expression product of said sequence, as between said control animal and said test animal.

10. A method of claim 9, wherein said animals are mammals.

11. A method of claim 10, wherein said mammals are rats.

12. A method for identifying a compound which inhibits or promotes the activity of a polynucleotide sequence of claim 1, comprising the steps of:

(a) selecting a host cell of claim 4;

(b) cloning said host cell and separating said clones into a test group and a control group;

(c) treating said test group using a compound; and

(d) deterning the relative quantity of an expression product of said sequence, as between said test group and said control group.

13. A method for identifying a compound which inhibits or promotes the activity of a polynucleotide sequence of claim 1, comprising the steps of:

(a) selecting a test group having a host cell of claim 4 or a part thereof, and selecting a suitable control group;

(b) treating said test group using a compound; and

(c) determining the relative quantity or relative activity of a product of said sequence or of the said sequence, as between said test group and said control group.

36. A composition for treating a PUFA disorder comprising a compound which modulates a sequence according to claims 1, 14 or 23 and a pharmaceutically acceptable carrier.

37. A composition as claimed in claim 36, wherein said disorder is selected from the group consisting eczema, cardiovascular, inflammation, Sjö

gren'"'"'s syndrome, gastrointestinal disorders, viral diseases and postviral fatigue, body weight disorders, psychiatric disorders, cancer, cystic fibrosis, endometriosis, pre-menstrual syndrome, alcoholism, congenital liver disease, Alzheimer'"'"'s syndrome, hypercholesterolemia, autoimmuune disorders, atopic disorders, acute respiratory distress syndrome, articular cartilage degradation, diabetes and diabetic complications.

38. A composition as claimed in claim 37, wherein said compound is selected from the group consisting of small organic molecules, peptides, polypeptides, antisense molecules, oligonucleotides, polynucleotides, fatty acids and derivatives thereof.

39. The use of a composition as claimed in claim 36 for treating PUFA disorders.

40. The use of claim 41, wherein said disorder is selected from the group consisting of eczema, cardiovascular, inflammation, Sjö

gren'"'"'s syndrome, gastrointestinal disorders, viral diseases and postviral fatigue, body weight disorders, psychiatric disorders, cancer, cystic fibrosis, endometriosis, pre-menstrual syndrome, alcoholism, congenital liver disease, Alzheimer'"'"'s syndrome, hypercholesterolemia, autoimmune disorders, atopic disorders, acute respiratory distress syndrome, articular cartilage degradation, diabetes and diabetic complications.

41. A method for diagnosing the presence of or a predisposition for a PUFA disorder in a subject by detecting a gernline alteration in a sequence of claims 1 or 23 in said subject, comprising comparing the germline sequence of a sequence of claims 1 or 23 from a tissue sample from said subject with the gerrnline sequence of a wild-type of said sequence, wherein an alteration in the germline sequence of said subject indicates the presence of or a predisposition to said PUFA disorder.

42. A method for diagnosing the presence of or a predisposition for a disorder as claimed in claim 41, wherein said disorder is selected from the group consisting of eczema, cardiovascular, inflammation, Sjö

gren'"'"'s syndrome, gastrointestinal disorders, viral diseases and postviral fatigue, body weight disorders, psychiatric disorders, cancer, cystic fibrosis, endometriosis, pre-menstrual syndrome, alcoholism, congenital liver disease, Alzheimer'"'"'s syndrome, hypercholesterolemia, autoimmune disorders, atopic disorders, acute respiratory distress syndrome, articular cartilage degradation, diabetes and diabetic complications.

43. The method of claims 41 to 42, wherein said comparing is performed by a method selected from the group consisting of immunoblotting, immunocytochemistry, enzyme-linked immunosorbent assay, DNA fingerprinting, in situ hybridization, polymerase chain reaction, reverse transcription polymerase chain reaction, radioiimmunoassay immunoradiometric assay and immunoenzymatic assay.

94. A composition as claimed in claim 36, wherein said compound is selected from the group in claim 90.

96. The use of a composition as claimed in any one of claims 94 to 95 for treating a PUFA disorder.

97. The use of claim 96, wherein said disorder is selected from the group consisting of eczema, cardiovascular, inflamnnation, Sjö

gren'"'"'s syndrome, gastrointestinal disorders, viral diseases and postviral fatigue, body weight disorders, psychiatric disorders, cancer, cystic fibrosis, endometriosis, pre-menstrual syndrome, alcoholism, congenital liver disease, Alzheimer'"'"'s syndrome, hypercholesterolemia, autoimmune disorders, atopic disorders, acute respiratory distress syndrome, articular cartilage degradation, diabetes and diabetic complications.

98. A compound identified by the methods of any one of claims 9 to 13, 18 to 22, 31 to 35, 47 to 61 or 76 to 82.

99. The use of a compound as claimed in claim 98 for treating a PUFA disorder.

100. The use as claimed in claim 99, wherein said disorder is selected from the group consisting of eczema, cardiovascular, inflammation, Sjö

gren'"'"'s syndrome, gastrointestinal disorders, viral diseases and postviral fatigue, body weight disorders, psychiatric disorders, cancer, cystic fibrosis, endometriosis, pre-menstrual syndrome, alcoholism, congenital liver disease, Alzheimer'"'"'s syndrome, hypercholesterolemia, autoimmune disorders, atopic disorders, acute respiratory distress syndrome, articular cartilage degradation, diabetes and diabetic complications.

107. The composition as claimed in any one of claims 37 and 65, wherein the cardiovascular disorder is selected from the group consisting of hype glyceridemia, dyslipideria, atherosclerosis, coronary artery disease, cerebrovascular disease and peripheral vascular disease.

108. The use as claimed in any one of claims 40, 68, 86, 97, 100, and 104, wherein the cardiovascular disorder sseeted from the group consisting of hypertriglyceridemia, dyslipidemia, atherosclerosis, coronary artery disease, cerebrovascular disease and peripheral vascular disease.

109. The method as claimed in any one of claims 42, 45, 71, 74, and 88, wherein the cardiovascular disorder is selected from the group consisting of hypertriglyceridemia, dyslipidemia, atherosclerosis, coronary artery disease, cerebrovascular disease and peripheral vascular disease.

110. The composition as claimed in any one of claims 37 and 65, wherein the inflammation is selected from the group consisting of sinusitis, asthma, pancreatitis, osteoarthritis, rheumatoid arthritis and acne.

111. The use as claimed in any one of claims 40, 68, 86, 97, 100, and 104, wherein the inflammation is selected from the group consisting of sinusitis, asthma, pancreatitis, osteoarthritis, rheumatoid arthritis and acne.

112. The method as claimed in any one of claims 42, 45, 71, 74, and 88, wherein the inflannation is selected from the group consisting of sinusitis, asthma, pancreatitis, osteoarthritis, rheumatoid arthritis and acne.

113. The composition as claimed in any one of claims 37 and 65, wherein the body weight disorder is selected from the group consisting of obesity, cachexia and anorexia.

114. The use as claimed in any one of claims 40, 68, 86, 97, 100, and 104, wherein the body weight disorder is selected from the group consisting of obesity, cachexia and anorexia.

115. The method as claimed in any one of claims 42, 45, 71, 74, and 88, wherein the body weight disorder is selected from the group consisting of obesity, cachexia and anorexia.

14. An isolated polypeptide comprising an isolated polypeptide selected from the group consisting of:

(a) a sequence comprising SEQ ID NO;

5;

(b) a sequence comprising SEQ ID NO;

9;

(c) a sequence comprising SEQ ID NO;

12;

(d) a sequence which is at least 80% homologous with a sequence of any of (a) to (c);

(e) a sequence which is at least 90% homologous with a sequence of any of (a) to (c);

(f) a sequence which is at least 95% homologous with a sequence of any of (a) to (c);

(g) a sequence which is at least 98% homologous with a sequence of any of (a) to (c); and

(h) a sequence which is at least 99% homologous with a sequence of any of (a) to (c).

15. A host cell comprising a polypeptide sequence of claim 14 in a host cell which is heterologous to said sequence.

16. A process for producing a polypeptide sequence of claim 14 comprising the step of culturing the host cell of claim 15 under conditions sufficient for the production of said polypeptide.

17. An isolated polypeptide sequence, comprising a polypeptide sequence which retains substantially the same biological function or activity as a polypeptide of claim 14.

18. A method for identifying a compound which inhibits or promotes the activity of a polypeptide sequence of claim 14, comprising the steps of:

(a) selecting a control animal having said sequence and a test animal having said sequence;

(b) treating said test animal using a compound;

(c) determining the relative quantity or relative activity of an expression product of said sequence or of the said sequence, as between said control animal and said test animal.

19. A method of claim 18, wherein said animals are mammals.

20. A method of claim 19, wherein said mamnmrals are rats.

21. A method for identifying a compound which inhibits or promotes the activity of a polypeptide sequence of claim 14, comprising the steps of:

(a) selecting a host cell of claim 15;

(b) cloning said host cell and separating said clones into a test group and a control group;

(c) treating said test group using a compound; and

(d) determining the relative quantity or relative activity of an expression product of said sequence or of the said sequence, as between said test group and said control group.

22. A method for identifying a compound which inhibits or promotes the activity of a polypeptide sequence of claim 14, comprising the steps of:

(a) selecting a test group having a host cell of claim 15 or a part thereof, and selecting a suitable control group;

(b) treating said test group using a compound; and

(c) determining the relative quantity or relative activity of a product of said sequence or of the said sequence, as between said test group and said control group.

44. A method for diagnosing the presence of or a predisposition for a PUFA disorder in a subject, comprising comparing the sequence of a polypeptide of claim 14 from a tissue sample from said subject with the sequence of a wild-type of said polypeptide, wherein an alteration in the sequence of said subject as compared to said wild-type indicates the presence of or a predisposition to said PUFA disorder.

45. A method for diagnosing the presence of or a predisposition for a disorder as claimed in claim 44, wherein said disorder is selected from the group consisting of eczema, cardiovascular, inflammnation, Sjö

gren'"'"'s syndrome, gastrointestinal disorders, viral diseases and postviral fatigue, body weight disorders, psychiatric disorders, cancer, cystic fibrosis, endometriosis, pre-menstrual syndrome, alcoholism, congenital liver disease, Alzheimer'"'"'s syndrome, hypercholesterolemia, autoimmune disorders, atopic disorders, acute respiratory distress syndrome, articular cartilage degradation, diabetes and diabetic complications.

46. The method of claims 44 to 45, wherein said comparing is performed by a method selected from the group consisting of blotting, immunocytochemistry, enzyme-linked immunosorbent assay, DNA fingerprinting, radioimmunoassay, imnmunoradiometric assay, immunoenzymatic assay and polypeptide microarrays.

90. An antibody immunoreactive with a polypeptide of claim 14 or an immunogenic portion thereof.

92. A method for screening a medium for an elongase polypeptide of claim 14 or selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6 and ELG7, comprising;

(a) labelling an antibody of any one of claims 90 to 91 with a marker molecule to form a conjugate;

(b) exposing said conjugate to said medium; and

(c) determining whether there is binding between said conjugate and a biomolecule in said medium, wherein said binding indicates the presence of said polypeptide.

93. A method for screening a medium for an elongase polypeptide of claim 14 or selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6 and ELG7, comprising:

(a) exposing an antibody of claims 91 to 92 to said medium;

(b) exposing said antibody to a marker molecule; and

(c) detemining whether there is binding between said marker molecule and a biomolecule in said medium, wherein said binding indicates the presence of said polypeptide.

23. An isolated polynucleotide sequence, comprising a polynucleotide sequence which is selected from the group consisting of:

(a) a sequence comprising SEQ ID NO;

1;

(b) a sequence comprising SEQ ID NO;

2;

(c) a sequence comprising SEQ ID NO;

3;

(d) a sequence comprising SEQ ID NO;

6;

(e) a sequence comprising SEQ ID NO;

7;

(f) a sequence comprising SEQ ID NO;

10;

(g) a sequence comprising SEQ ID NO;

13;

(h) a sequence which is at least 80% homologous with a sequence of any of (a) to (g);

(i) a sequence which is at least 90% homologous with a sequence of any of (a) to (g);

(j) a sequence which is at least 95% homologous with a sequence of any of (a) to (g);

(k) a sequence which is at least 98% homologous with a sequence of any of (a) to (g);

(l) a sequence which is at least 99% homologous with a sequence of any of (a) to (g); and

;

(m) a sequence which hybridizes to any of (a) to (l) under stringent conditions.

24. An isolated polynucleotide sequence of claim 23, wherein the isolated polynucleotide sequence is genomic DNA.

25. A vector comprising a polynucleotide sequence of claim 23 in a suitable vector.

26. A host cell comprising a polynucleotide sequence of claim 23 in a host cell which is heterologous to said sequence.

27. A process for producing a polypeptide encoded by a gene operably linked to a polynucleotide sequence of claim 23 comprising the step of culturing the host cell of claim 26 under conditions sufficient for the production of said polypeptide.

28. An isolated polynucleotide fragment selected from the group consisting of:

(a) a sequence having at least 15 sequential bases of nucleotides of a sequence of claim 23;

(b) a sequence having at least 30 sequential bases of nucleotides of a sequence of claim 23;

and

(c) a sequence having at least 50 sequential bases of nucleotides of a sequence of claim 23.

29. A vector comprising a polynucleotide sequence of claim 28 contained in a vector which is heterologous to said sequence.

30. An isolated polynucleotide sequence, comprising a polynucleotide sequence which has substantially the same biological function or activity or is a functional derivative of a sequence of claim 23.

31. A method for identifying a compound which inhibits or promotes the activity of a polynucleotide sequence of claim 23, comprising the steps of:

(a) selecting a control animal having said sequence and a test animal having said sequence;

(b) treating said test animal using a compound; and

,

(c) determining the relative quantity of an expression product of an operably linked polynucleotide to said sequence, as between said control animal and said test animal.

32. A method of claim 31, wherein said animals are mammals.

33. A method of claim 32, wherein said mammals are rats.

34. A method for identifying a compound which inhibits or promotes the activity of a polynucleotide sequence of claim 23, comprising the steps of:

(a) selecting a host cell of claim 26;

(b) cloning said host cell and separating said clones into a test group and a control group;

(c) treating said test group using a compound; and

(d) determining the relative quantity of an expression product of an operably linked polynucleotide to said sequence, as between said test group and said control group.

35. A method for identifying a compound which inhibits or promotes the activity of a polynucleotide sequence of claim 23, comprising the steps of:

(a) selecting a test group having a host cell of claim 26 or a part thereof, and selecting a suitable control group;

(b) treating said test group using a compound; and

(c) determining the relative quantity of an expression product of an operably linked polynucleotide to said sequence, as between said test group and said control group.

47. A method for identifying a compound which modulates a PUFA disorder, comprising identifying a compound which modulates the activity of a polynucleotide, wherein the polynucleotide is a coding sequence selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6 and ELG7, comprising the steps of:

(a) selecting a control animal having said polynucleotide and a test animal having said polynucleotide;

(b) treating said test animal using a compound; and

,

(c) detenrmining the relative quantity of an expression product of said polynucleotide, as between said control animal and said test animal.

48. A method of claim 47, wherein said animals are mammnals.

49. A method of claim 48, wherein said mammals are rats.

50. A method for identifyring a compound which modulates a PUFA disorder, comprising identifying a compound which modulates the activity of a polynucleotide, wherein the polyncleotide is acoding sequence selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6 and ELG7, comprising the steps of:

(a) selectingahost cell having said polynucleotide, wherein said host cell is heterologous to said polynucleotide;

(b) cloning said host cell and separating said clones in to a test group and a control group;

(c) treating said test group using a compound; and

(d) determining the relative quantity of an expression product of said polynucleotide, as between said test group and said control group.

51. A method for identifying a compound which modulates a PUFA disorder, comprising identifying a compound which modulates the activity of a polynucleotide, wherein the polynucleotide is a coding sequence selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6 and ELG7, comprising the steps of:

(a) selecting a test group having a host cell with said polynucleotide or a portion of said host cell, and selecting a suitable control group;

(b) treating said test group using a compound; and

(c) determining the relative quantity or relative activity of a product of said polynucleotide or of the said polyiiucleotide, as between said test group and said control group.

52. A method for identifyig a compound modulates a PUFA disorder, comprising identifying a compound which modulates the activity of a polypeptide selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6 and ELG7, comprising the steps of:

(a) selecting a control animal having said polypeptide and a test animal having said polypeptide;

(b) treating said test animal using a compound;

(c) determining the relative quantity or relative activity of an expression product of said polypeptide or of the said polypeptide, as between said control animal and said test animal.

53. A method of claim 52, wherein said animals are mammals.

54. A method of claim 53, wherein said mammals are rats.

55. A method for identifying a compound which modulates a PUFA disorder, comprising identifying a compound which modulates the activity of a polypeptide selected from the group consisting of ELG 1, ELG2, ELG3, ELG4, ELG5, ELG6 and ELG7, comprising the steps of:

(a) selecting a host cell comprising said polypeptide wherein said host cell is heterologous to said polypeptide;

(b) cloning said hostcell and sepirating said clones into a test group and a control group;

(c) treating said test group using a compound; and

(d) determining the relative quantity or relative activity of an expression product of said polypeptide or of the said polypeptide, as between said test group and said control group.

56. A method for identifying a compound which modulates a PUFA disorder, comprising identifying a compound which modulates the activity of a polypeptide selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6 and ELG7, comprising the steps of:

(a) selecting a test group having a host cell with said polynucleotide or a portion of said host cell, and selecting a suitable control group;

(b) treating said test group using a compound; and

(c) determining the relative quantity or relative activity of a product of said polypeptide or of the said polypeptide, as between said test group and said control group.

57. A method for identifying a compound which modulates the activity of a polynucleotide, wherein the polynucleotide is a control region of a gene selected from the group consisting of ELG1, ELG2, ELG3, ELG4,ELG5, ELG6 and ELG7, comprising the steps of:

(a) selecting a control animal having said polynucleotide and a test animal having said polynucleotide;

(b) treating said test animal using a compound; and

,

(c) determining the relative quantity of an expression product of an operably linked polynucleotide to said polynucleotide, as between said control animal and said test animal.

58. A method of claim 57, wherein said animals are mammals.

59. A method of claim 58, wherein said maimnals are rats.

60. A method for identifying a compound which modulates the activity of a polynucleotide, wherein the polynucleotide is a control region of a gene selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6 and ELG7, comprising the steps of:

(a) selecting a host cell comprising said polynucleotide, wherein said host cell is heterologous to said polynucleotide;

(b) cloning said host cell and separating said clones into a test group and a control group;

(c) treating said test group using a compound; and

(d) determining the relative quantity of an expression product of an operably linked polyriucleotide to said polynucleonde, as between said test group and said control group.

61. A method for identifying a compound which modulates the activity of a polynucleotide, wherein the polynucleotide is a control region of a gene selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6 and ELG7, comprising the steps of:

(a) selecting a test group having a host cell with said polynucleotide or a portion of said host cell, and selecting a suitable control group;

(b) treating said test group using a compound; and

(c) determining the relative quantity of an expression product of an operably linked polynucleotide to said polynucleotide, as between said test group and said control group.

62. A composition for treating a PUFA disorder comprising a compound which modulates a polynucleotide from the coding sequence selected from the grpup consisting of ELG1, ELG2, ELG3, ELG4, ELGS, ELG6, and ELG7, and a pharmaceutically acceptable carrier.

65. A composition as claimed in any one of claims 62 to 64, wherein said disorder is selected from the group consisting of eczema, cardiovascular, inflammation, Sjö

gren'"'"'s syndrome, gastrointestinal disorders, viral diseases and postviral fatigue, body weight disorders, psychiatric disorders, cancer, cystic fibrosis, endometriosis, pre-menstrual syndrome, alcoholism, congenital liver disease, Alzheimer'"'"'s syndrome, hypercholesterolemia, autoimmune disorders, atopic disorders, acute respiratory distress syndrome, articular cartilage degradation, diabetes and diabetic complications.

66. A composition as claimed in any one of claims 62 to 64, wherein said compound is selected from the group consisting of small organic molecules, peptides, polypeptides, antisense molecules, oligonucleotides, polynucleotides, fatty acids and derivatives thereof.

67. The use of a composition as claimed in any one of claims 62 to 64 for treating PUFA disorders.

68. The use of claim 67, wherein said disorder is selected from the group consisting of eczema, cardiovascular, inflammation, Sjö

gren'"'"'s syndrome, gastrointestinal disorders, viral diseases and postviral fatigue, body weight disorders, psychiatric disorders, cancer, cystic fibrosis, endometriosis, pre-menstrual syndrome, alcoholism, congenital liver disease, Alzheimer'"'"'s syndrome, hypercholesterolemia, autoimmune disorders, atopic disorders, acute respiratory distress syndrome, articular cartilage degradation, diabetes and diabetic complications.

95. A composition as claimed in any one of claims 62 to 64, wherein said compound is selected from the group consisting of antibodies against ELG1, ELG2, ELG3 and ELG5.

63. A composition for treating a PUFA disorder comprising a compound which modulates a polypeptide selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6, and ELG7, and a pharmaceutically acceptable carrier.

64. A composition for treating a PUFA disorder comprising a compound which modulates a polynucleotide from the control region selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6, and ELG7, and a pharmaceutically acceptable carrier.

69. A method for diagnosing the presence of or a predisposition for a PUFA disorder in a subject by detecting a germline alteration in a polynucleotide representing .the coding sequence selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6, and ELG7, from said subject, comprising comparing the germline sequence of said polynucleotide from a tissue sample from said subject with the germline sequence of a wild-type of said polynucleotide, wherein an alteration in the germline sequence of said subject indicates the presence of or a predisposition to said PUFA disorder.

71. A method for diagnosing the presence of or a predisposition for a disorder as claimed in any one of claims 69 to 70, wherein said disorder is selected from the group consisting of eczema, cardiovascular, inflammation, Sjö

gren'"'"'s syndrome, gastrointestinal disorders, viral diseases and postviral fatigue, body weight disorders, psychiatric disorders, cancer, cystic fibrosis, endometriosis, pre-menstrual syndrome, alcoholism, congenital liver disease, Alzheimer'"'"'s syndrome, hypercholesterolemia, autoimmune disorders, atopic disorders, acute respiratory distress syndrome, articular cartilage degradation, diabetes and diabetic complications.

72. The method of claims 69 to 71, wherein said comparing is performed by a method selected from the group consisting of ininunoblotting, immunocytochemistry enzyme-linked immunosorbent assay, DNA fingerprinting, in situ hybridization, polymerase chain reaction, reverse transcription polymerase chain reaction, radioimmunoassay, immunoradiometric assay and immunoenzymatic assay.

70. A method for diagnosing the presence of or a predisposition for a PUFA disorder in a subject by detecting a germline alteration in a polynucleotide representing the control region selected from the group consisting of ELG1, ELG2, ELG3 and ELG5 in said subject, comprising comparing the gerinline sequence of said polynucleotide from a tissue sample from said subject with the germline sequence of a wild-type of said polynucleotide, wherein an alteration in the germline sequence of said subject indicates the presence of or a predisposition to said PUFA disorder.

73. A method for diagnosing the presence of or a predisposition for a PUFA disorder in a subject, comprising comparing the sequence of a polypeptide selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6, and ELG7, from said subject with the sequence of a wild-type of said polypeptide, wherein an alteration in the sequence of said subject as compared to said wild-type indicates the presence of or a predisposition to said PUFA disorder.

74. A method for diagnosing the presence of or a predisposition for a disorder as claimed in claim 73, wherein said disorder is selected from the group consisting of eczema, cardiovascular, inflammation, Sjö

gren'"'"'s syndrome, gastrointestinal disorders, viral diseases and postviral fatigue, body weight disorders, psychiatric disorders, cancer, cystic fibrosis, endometriosis, pre-menstrual syndrome, alcoholism, congenital liver disease, Alzheimer'"'"'s syndrome, hypercholesterolemia, autoimmune disorders, atopic disorders, acute respiratory distress syndrome, articular cartilage degradation, diabetes and diabetic complications.

75. The method of claims 73 to 74, wherein said comparing is performed by a method selected from the group consisting of immunoblotting, immunocytochemistry, enzyme-linked immunosorbent assay, DNA fingerprinting, radioimmunoassay, immunoradiometric assay, immunoenzymatic assay and polypeptide microarrays.

76. A method for identifying a compound which inhibits or promotes the overall activity of two or more polynucleotides, wherein the polynucleotides are control regions of two or more different genes selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6 and ELG7, comprising the steps of:

(a) selecting a host cell having said polynucleotides, wherein said host cell is heterologous to said polynucleotides;

(b) cloning said host cell and separating said clones into a test group and a control group;

(c) treating said test group using a compound; and

(d) determining the relative quantities of expression products of operably linked polynucleotides to said poly ucleotides, as between said test group and said control group.

77. A method for Identifying a compound which inhibits or promotes the overall activity of two or more polynucleotides, wherein the polynucleotides are from control regions of said polynucleotides, selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6 and ELG7, comprising the steps of:

(a) selecting a test group having a host cell with said polynucleotide or a portion of said host cell, and selecting a suitable control group;

(b) treating said test group using a compound; and

(c) determining the relative quantities of expression products of operably linked polynucleotides to said polynucleotides, as between said test group and said control group.

78. A method for identifying a compound which inhibits or promotes the activity of two or more polynucleotides, wherein the polynucleotides are coding sequences selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELGS, ELG6 and ELG7, operably associated with promoter regions, wherein the promoter regions are effective to initiate, terminate or

(a) selecting a host cell having said polynucleotides, wherein said host cell are heterologous to said polynucleotides;

(b) cloning said host cell and separating said clones into a test group and a control group;

(c) treating said test group using a compound; and

(d) determining the relative quantity or relative activity of an expression product of said polynucleotide, as between said test group and said control group.

79. A method for identifying a compound which inhibits or promotes the activity of two or more polynucleotides, wherein the polynucleotides are coding sequences selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6 and ELG7, operably associated with promoter regions, wherein the promoter regions are effective to initiate, terminate or regulate the level of expression of the nucleic acid sequence, comprising the steps of:

(a) selecting a test group having a host cell with said polynucleotide or a portion of said host cell, and selecting a suitable control group;

(b) treating said test group using a compound; and

(c) determining the relative quantity or relative activity of an expression product of said polynucleotide, as between said test group and said control group.

80. A method for identifying a compound which inhibits or promotes the activity of a mammalian delta-5-desaturasenzyme and one or more enzymes selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6, or ELG7, within the same host system, comprising the steps of:

(a) providing a host system containing nucleic acid sequences which encode for a mammalian delta-5-desaturase and one or more mammnualian elongase enzymes selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6 or ELG7, operably associated with promoter regions, wherein the promoter regions are effective to initiate, terminate or regulate the level of expression of the nucleic acid sequence;

(b) contacting the host system with a test component;

(c) simultaneously evaluating the enzymatic activities of the delta-5-desaturase and the elongase enzymes, wherein a measurable difference in a level of lipid metabolites or associated cofactors in the presence of the test component compared to a control under identical conditions but in the absence of the test component is an indicator of the ability of the test component to modulate delta-5-desaturase and/or elongase enzyme activity; and

(d) identifying as said compound a test component which exhibits said ability.

81. A method for identifyjng a compound which inhibitsr promotes the activity of a mammalian delta-6-desaturase enzyme and one or more enzymes selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6 or ELG7, within the same host system, comprising the steps of:

(a) providing a host system containing nucleic acid sequences which encode for a mammalian delta-6-desaturase and one or more manunalian elongase enzymes selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6 or ELG7, operably associated with promoter regions, wherein the promoter regions are effective to initiate, terminate or regulate the level of expression of the nucleic acid sequence;

(b) contacting the host system with a test component;

(c) simultaneously evaluating the enzymatic activities of the delta-6-desaturase and the elongase enzymes, wherein a measurable difference in a level of lipid metabolites or associated cofactors in the presence of the test component compared to a control under identical conditions but in the absence of the test component is an indicator of the ability of the test component to modulate delta-6-desaturase and/or elongase enzyme activity; and

(d) identifying as said compound a test component which exhibits said ability.

82. A method for identifying a compound which inhibits or promotes the activity of a mammalian delta-5- and delta-6-desaturase enzyme and/or one or more enzymes selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6 or ELG7, within the same host system, comprising the steps of:

(a) providing a host system containing nucleic acid sequences which encode simultaneously for a mammalian delta-5-desaturase, a mammalian delta-6-desaturase and one or more mammalian elongase enzymes selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6 or ELG7, operably associated with promoter regions, wherein the promoter regions are effective to initiate, terminate or regulate the level of expression of the nucleic acid sequence;

(b) contacting the host system with a test component;

(c) simultaneously evaluating the enzymatic activities of the delta-5-desaturase, the delta-6-desaturase and the elongase enzymes, wherein a measurable difference in a level of lipid metabolites or associated cofactors in the presence of the test component compared to a control under identical conditions but in the absence of the test component is an indicator of the ability of the test component to modulate delta-5- and/or delta-6-desaturase and/or elongase enzyme activity; and

(d) identifying as said compound a test component which exhibits said ability.

83. A cpition for treating a PUFA disorder comprising a compound which modulates two or more human polynucleotides from control regions selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6, ELG7, delta-5-desaturase, delta-6-desaturase and a pharmaceutically acceptable carrier.

84. A composition as claimed in claim 83, wherein said compound is selected from the group consisting of small organic molecules, peptides, polypeptides, antisense molecules, oligonucleotides, polynucleotides, fatty acids and derivatives thereof.

85. The use of a composition as claimed in claim 84 for treating PUFA disorders.

86. The use of claim 85, wherein said disorder is selected from the group consisting of eczema, cardiovascular, inflammation, Sjö

gren'"'"'s syndrome, gastrointestinal disorders, viral diseases and postviral fatigue, body weight disorders, psychiatric disorders, cancer, cystic fibrosis, endometriosis, pre-menstrual syndrome, alcoholism, congenital liver disease, Alzheimer'"'"'s syndrome, hypercholesterolemia, autoimmune disorders, atopic disorders, acute respiratory distress syndrome, articular cartilage degradation, diabetes and diabetic complications.

87. A method for detecting the presence of or the predisposition for a PUFA disorder, said method comprising determining the level of expression of two or more expression products of genes selected from the group onsisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6, ELG7, delta-5-desaturase, delta-6-desaturase, in a subject relative to a predetermined control level of expression, wherein any modified expression of said expression products as compared to said control is indicative of the presence of or the predisposition for a PUFA disorder.

88. A method of claim 87, wherein said disorder is selected fom a group consisting of eczema, cardiovascular inflammation, Sjö

gren'"'"'s syndrome gastrointestinal disorders viral diseases and postviral fatigue, body weight disorders, psychiatric disorders, cancer, cystic fibrosis, endometriosis, premenstrual syndrome, alcoholism, congenital liver disease, Alzheimer'"'"'s syndrome, hypercholesterolemia, autoimmune disorders, atopic disorders, acute respiratory distress syndrome, articular cartilage degradation, diabetes and diabetic complications.

89. A method of claims 87 to 88, wherein said method is selected from the group consisting of immunoblotting, immunocytochemistry, enzyme-linked immunosorbent assay, in situ hybridization, reverse transcription polymerase chain reaction, radioimmunoassay, immunoradiometric assay, immunoenzymatic assay and polynucleotide and polypeptide microarrays.

91. An antibody immunoreactive with an elongase polypeptide selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6 and ELG7, or an immunogenic portion thereof.

101. A method for diagnosing the presence of or a predisposition for a PUFA disorder in a subject by detecting alterations as compared to wild-type in the elongation of PUFA in a peripheral blood leukocyte obtained from said subject.

102. A method for monitoring the development of a PUFA disorder in a subject by detecting alterations as compared to previous samples in the elongation of PUFA in a peripheral blood leukocyte obtained from said subjects.

103. A method for assessing the efficacy of test compounds on a PUFA disorder in a subject by assessing alterations as compared to previous samples in the elongation of PUFA in a peripheral blood leukocyte obtained from said subject.

104. The use of pebulate sulphoxide for the treatment of a disease selected from the group consisting of eczema, cardiovascular, inflammation, Sjö

gren'"'"'s syndrome, gastrointestinal disorders, viral diseases and postviral fatigue, body weight disorders, psychiatric disorders, cancer, cystic fibrosis, endometriosis, pre-menstrual syndrome, alcoholism, congenital liver disease, Alzheimer'"'"'s syndrome, hypercholesterolemia, autoimmune disorders, atopic disorders, acute respiratory distress syndrome, articular cartilage degradation, diabetes and diabetic complications.

105. A method for idenitiying a compound which modulates a biological activity of a polypeptide selected from the group consisting of ELG1, ELG2, ELG3, ELG4, ELG5, ELG6 and ELG7, comprising the steps of:

(a) providing an assay which measures a biological activity of the selected polypeptide;

(b) treating the assay with a compound; and

(c) identifying a change in the biological activity of the selected polypeptide, wherein a difference between the treated assay and a control assay identifies the compound as modulator of the polypeptide.

106. The method of claim 105, wherein the selected polypeptide is provided in an assay format selected from among a purified protein, reconstituted protein, cell extract and a whole cell assay.