Methods for identification of alport syndrome

• US 7,285,388 B1
• Filed: 06/12/2006
• Issued: 10/23/2007
• Est. Priority Date: 04/07/2006
• Status: Expired due to Fees

• Current Assignee: Ashley G. Davidson, George E. Lees, Keith E. Murphy
• Original Assignee: Merlogen LLC
• Inventors: Murphy, Keith E., Lees, George E., Davidson, Ashley G.
• Primary Examiner(s): Goldberg; Jeanine A.
• Application Number:
  US11/423,650
• Publication Number:
  US 20070243538A1
• Time in Patent Office: 498 Days
• Field of Search: None
• US Class Current: 435/6.18
• 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: C12Q 2600/172 Haplotypes

Abstract

Animals with mutations in COL4a4 present with autosomal recessive Alport Syndrome (ARAS). Through sequencing of COL4a4, the mutation causative for ARAS in the English Cocker Spaniel (ECS) has been identified. The resulting protein is severely truncated due to a premature stop codon in exon 3. This nonsense mutation occurs in the 7S domain and also causes the loss of the entire collagenous and NC1 domains of the protein. Methods for the identification of animals that harbor a mutation in the COL4a4 gene are described. Mutations in the COL4a4 gene can be identified from any biological sample such as a cell or tissue that contains genomic DNA. Methods for identifying single nucleotide polymorphisms (SNPs) that are inherited with the disease are also described. A microsatellite marker that segregates with ARAS is also described that was identified using linkage disequilibrium mapping.

Claims

1. A method of detecting in a dog a mutation that causes autosomal recessive Alport Syndrome in English Cocker Spaniels comprising

a) obtaining a biological sample from the dog;

b) analyzing the biological sample for SEQ ID NO;

90;

wherein the presence of SEQ ID NO;

90 is indicative of a dog carrying a mutation that causes Alport Syndrome in English Cocker Spaniels.

2. A method of detecting in a dog a mutation that causes autosomal recessive Alport Syndrome in English Cocker Spaniels comprising

a) obtaining a biological sample from the dog;

b) analyzing the biological sample for a single nucleotide polymorphism 93 bases upstream of exon 42 in canine COL4A4;

wherein the presence of a T to A substitution 93 bases upstream of exon 42 in canine COL4A4 is indicative of a dog carrying a mutation that causes Alport Syndrome in English Cocker Spaniels.

3. A method of detecting in a dog a mutation that causes autosomal recessive Alport Syndrome in English Cocker Spaniels comprising

a) obtaining a biological sample from the dog;

b) analyzing the biological sample for a single polynucleotide polymorphism 90 bases upstream of exon 42 in canine COL4A4;

wherein the presence of a T to C substitution 90 bases upstream of exon 42 in canine COL4A4 is indicative of a dog carrying a mutation that causes Alport Syndrome in English Cocker Spaniels.

4. A method of detecting in a dog a mutation that causes autosomal recessive Alport Syndrome in English Cocker Spaniels comprising

a) obtaining a biological sample from the dog;

b) analyzing the biological sample for a single polynucleotide polymorphism 32 bases upstream of exon 3 in canine COL4A4;

wherein the presence of a T to C substitution 32 bases upstream of exon 3 in canine COL4A4 is indicative of a dog carrying a mutation that causes Alport Syndrome in English Cocker Spaniels.