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NATURALLY‐OCCURRING MISSENSE MUTATIONS IN THE CANINE CFTR GENE
Author(s) -
Spadafora Domenico,
Hawkins Eleanor C,
Ballard Stephen T
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.772.1
Subject(s) - missense mutation , bronchiectasis , cystic fibrosis , medicine , pancreatitis , mutation , pathology , gastroenterology , gene , genetics , biology , lung
Naturally‐occurring, cystic fibrosis‐causing mutations in the CFTR have not been identified in any non‐human animal species. Since domestic dogs are known to develop medical conditions associated with atypical CF in humans, (e.g. idiopathic bronchiectasis, pancreatitis, and aplasia of the vas deferens), we hypothesized that some dogs also carry CFTR mutations. Temporal temperature‐gradient gel electrophoresis (TTGE) was used to screen dogs for CFTR mutations. Canine whole blood was obtained from veterinary clinics and diagnostic laboratories. We screened DNA from 290 dogs that fell into one of three categories: dogs diagnosed with pancreatitis, dogs diagnosed with bronchiectasis, and dogs admitted to clinics for any illness (at‐large dogs). Thus far, 24 dogs have been identified with one of four missense mutations: R812W, P1281T, R1456W and P1464H. P1281T and P1464H mutations occur in relatively unconserved residues. R1456W is analogous to the human R1453W mutation, which has about 20% of normal CFTR function and is associated with pancreatitis and panbronchiolitis. R812W is in a highly conserved region of the regulatory domain. Mutation frequencies in pancreatitis and bronchiectasis animals were found at about twice the frequency of at‐large dogs. We conclude that naturally occurring CFTR mutations are relatively common in domestic dogs and can be detected with TTGE. Supported by NIH HL633002 and Cystic Fibrosis Foundation grant BALLAR07G0