CYSTIC FIBROSIS GENE MUTATIONS

• US 20140178870A1
• Filed: 04/29/2013
• Published: 06/26/2014
• Est. Priority Date: 03/05/2004
• Status: Active Grant

• Current Assignee: Quest Diagnostics Investments Incorporated (Quest Diagnostics Incorporated)
• Original Assignee: Quest Diagnostics Investments Incorporated (Quest Diagnostics Incorporated)
• Inventors: McGinniss, Matthew J., Buller, Arlene M., Quan, Franklin, Peng, Mei, Sun, Weimin
• Granted Patent: US 9,228,237 B2
• Time in Patent Office: Days
• US Class Current: 435/6.11
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]

Abstract

The present invention provides novel mutations of the CFTR gene related to cystic fibrosis or to conditions associated with cystic fibrosis. Also provided are probes for detecting the mutant sequences. Methods of identifying if an individual has a genotype containing one or more mutations in the CFTR gene are further provided.

Claims

1-11. -11. (canceled)

12. A method of detecting a mutant cystic fibrosis transmembrane (CFTR) nucleic acid in an individual, comprising

a) assaying a biological sample comprising a CFTR nucleic acid from the individual, and

b) detecting a mutation in the CFTR nucleic acid wherein the mutation is selected from the group consisting of c.473G>

C, c.1072G>

A, c.1441A>

G, c.1472G>

C,

c.2817_—

2821 del, c.2846A>

T, and c.3107C>

A, and

13. The method of claim 12, wherein the assaying comprises nucleic acid sequencing.

14. The method of claim 12, comprising amplifying one or more portion(s) of the CFTR nucleic acid using primers directed to a portion of the CFTR nucleic acid sequence that contains the mutation.

15. The method of claim 13, comprising sequencing all or a portion of the CFTR gene in genomic DNA from the biological sample.

16. The method of claim 12, comprising sequencing mRNA from the biological sample or cDNA produced from the mRNA.

17. The method of claim 12, comprising performing restriction fragment length polymorphism analysis following treatment of the CFTR nucleic acid with at least one endonuclease restriction enzyme.

18. The method of claim 12, comprising performing allele specific amplification.

19. The method of claim 12, comprising performing primer extension.

20. The method of claim 12, comprising performing oligonucleotide ligation.

21. The method of claim 12, comprising performing hybridization with a detectably labeled probe.

22. The method of claim 21 wherein the probe comprises a portion of the CFTR sequence that comprises the mutation.

23. A method of determining the cystic fibrosis status of a human, comprising:

(a) assaying a biological sample comprising a CFTR nucleic acid from the human;

(b) determining the presence of a mutation in one or both alleles of the CFTR gene in the human, wherein the mutation is selected from the group consisting of c.473G>

C, c.1072G>

A, c.1441A>

G, c.1472G>

C, c.2817_—

2821 del, c.2846A>

T, and c.3107C>

A, and

(c) identifying the human;

(i) as having cystic fibrosis or being predisposed to cystic fibrosis when the human is homozygous for the mutation in the CFTR gene, thereby correlating the human with having cystic fibrosis;

or

(ii) as being a cystic fibrosis carrier when the human is heterozygous for the mutation in the CFTR gene thereby correlating the human with having a predisposition for cystic fibrosis.

24. The method of claim 23, wherein the assaying comprises nucleic acid sequencing.

25. The method of claim 23, comprising amplifying one or more portion(s) of the CFTR nucleic acid using primers directed to a portion of the CFTR nucleic acid sequence that contains the mutation.

26. The method of claim 23, comprising sequencing all or a portion of the CFTR gene in genomic DNA from the biological sample.

27. The method of claim 23, comprising sequencing mRNA from the biological sample or cDNA produced from the mRNA.

28. The method of claim 23, comprising performing restriction fragment length polymorphism analysis following treatment of the CFTR nucleic acid with at least one endonuclease restriction enzyme.

29. The method of claim 23, comprising performing allele specific amplification.

30. The method of claim 23, comprising performing primer extension.

31. The method of claim 23, comprising performing oligonucleotide ligation.

32. The method of claim 23, comprising performing hybridization with a detectably labeled probe.

33. A method of determining if a human is predisposed to cystic fibrosis comprising:

(a) assaying a biological sample comprising a CFTR nucleic acid from the human;

(b) determining the presence of a mutation in one or both alleles of the CFTR gene in the human, wherein the mutation is selected from the group consisting of c.473G>

C, c.1072G>

A, c.1441A>

G, c.1472G>

C, c.2817_—

2821del, c.2846A>

T, and c.3107C>

A, and

(c) identifying said human as;

(i) being predisposed to cystic fibrosis when the human is homozygous for the mutation in the CFTR gene, or

(ii) having no predisposition to cystic fibrosis when the human is heterozygous for the mutation in the CFTR gene.

34. A method of identifying a human as having an increased likelihood of having an offspring afflicted with cystic fibrosis, comprising:

(a) assaying a biological sample comprising a CFTR nucleic acid from the human;

(b) determining the presence of a mutation in one or both alleles of the CFTR gene in the human, wherein the mutation is selected from the group consisting of c.473G>

C, c.1072G>

A, c.1441A>

G, c.1472G>

C, c.2817_—

2821del, c.2846A>

T, and c.3107C>

A, and

(c) identifying said human as having an increased likelihood of having an offspring afflicted with cystic fibrosis when the mutation is detected in at least one allele.