Comparative genomic sequence analysis of the human and mouse cystic fibrosis transmembrane conductance regulator genes

Ellsworth, Rachel E.; Jamison, D. Curtis; Touchman, Jeffrey W.; Chissoe, Stephanie L.; Maduro, Valerie V.; Bouffard, Gerard G.; Dietrich, Nicole; Beckstrom-Sternberg, Stephen M.; Iyer, Leslie M.; Weintraub, Lauren; Cotton, Marc; Courtney, Laura; Edwards, Jennifer; Maupin, Rachel; Ozersky, Philip; Rohlfing, Theresa; Wohldmann, Patricia; Miner, Tracie L.; Kemp, K.; Kramer, Jason; Korf, Ian F; Pepin, Kimberlie; Antonacci-Fulton, Lucinda; Fulton, Robert S.; Minx, Patrick; Hillier, LaDeana W.; Wilson, Richard K.; Waterston, Robert H.; Miller, Webb; Green, Eric D.

doi:10.1073/pnas.97.3.1172

Cited by 64 publications

(39 citation statements)

References 67 publications

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“…The murine CFTR gene spans approximately 152 kb with all 27 exons being highly similar to the human homologue (Ellsworth et al 2000). The murine CFTR protein is very similar to the human (78% identity) and the majority of known CF mutations occur in well-conserved regions suggesting conservation of function across species.…”

Section: Cf Mice Models and Lung Diseasementioning

confidence: 99%

Animal models of chronic lung infection with Pseudomonas aeruginosa: useful tools for cystic fibrosis studies

Kukavica-Ibrulj

Levesque

2008

Lab Anim

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SummaryCystic fibrosis (CF) is caused by a defect in the transmembrane conductance regulator (CFTR) protein that functions as a chloride channel. Dysfunction of the CFTR protein results in salty sweat, pancreatic insufficiency, intestinal obstruction, male infertility and severe pulmonary disease. In most patients with CF life expectancy is limited due to a progressive loss of functional lung tissue. Early in life a persistent neutrophylic inflammation can be demonstrated in the airways. The cause of this inflammation, the role of CFTR and the cause of lung morbidity by different CF-specific bacteria, mostly Pseudomonas aeruginosa, are not well understood. The lack of an appropriate animal model with multi-organ pathology having the characteristics of the human form of CF has hampered our understanding of the pathobiology and chronic lung infections of the disease for many years. This review summarizes the main characteristics of CF and focuses on several available animal models that have been frequently used in CF research. A better understanding of the chronic lung infection caused particularly by P. aeruginosa, the pathophysiology of lung inflammation and the pathogenesis of lung disease necessitates animal models to understand CF, and to develop and improve treatment.

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Section: Cf Mice Models and Lung Diseasementioning

confidence: 99%

Animal models of chronic lung infection with Pseudomonas aeruginosa: useful tools for cystic fibrosis studies

Kukavica-Ibrulj

Levesque

2008

Lab Anim

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“…The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene located on chromosome 7q31.2, which when mutated causes CF, spans approximately 190 kb of genomic DNA (Ellsworth et al 2000). Several research groups constructed 1.5Mb Yeast Artificial Chromosome (YAC) contigs encompassing the CFTR genomic locus.…”

Section: Cftr Gene Structure and Organisationmentioning

confidence: 99%

The Phenotypic Consequences of CFTR Mutations

Rowntree¹,

Harris²

2003

Annals of Human Genetics

298

215

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SummaryCystic fibrosis is a common autosomal recessive disorder that primarily affects the epithelial cells in the intestine, respiratory system, pancreas, gall bladder and sweat glands. Over one thousand mutations have currently been identified in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene that are associated with CF disease. There have been many studies on the correlation of the CFTR genotype and CF disease phenotype; however, this relationship is still not well understood. A connection between CFTR genotype and disease manifested in the pancreas has been well described, but pulmonary disease appears to be highly variable even between individuals with the same genotype. This review describes the current classification of CFTR mutation classes and resulting CF disease phenotypes. Complex disease alleles and modifier genes are discussed along with alternative disorders, such as disseminated bronchiectasis and pancreatitis, which are also thought to result from CFTR mutations.

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“…The initial shotgun phase of BAC sequencing was performed by using well-established methods (Wilson and Mardis 1997a,b;Ellsworth et al 2000;DeSilva et al 2002;Thomas et al 2003). In brief, plasmid subclones containing 3-to 5-kb inserts (produced by physically shearing purified BAC DNA) were derived from each BAC, and sequence reads were generated from both ends of randomly selected subclones (forward and reverse "read pairs") to provide at least eightfold average coverage in high-quality (Phred Q20) bases.…”

Section: Generation Of Comparative-grade Finished Sequencementioning

confidence: 99%

An intermediate grade of finished genomic sequence suitable for comparative analyses

Blakesley

Hansen²,

Mullikin³

et al. 2004

Genome Res.

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Although the cost of generating draft-quality genomic sequence continues to decline, refining that sequence by the process of "sequence finishing" remains expensive. Near-perfect finished sequence is an appropriate goal for the human genome and a small set of reference genomes; however, such a high-quality product cannot be cost-justified for large numbers of additional genomes, at least for the foreseeable future. Here we describe the generation and quality of an intermediate grade of finished genomic sequence (termed comparative-grade finished sequence), which is tailored for use in multispecies sequence comparisons. Our analyses indicate that this sequence is very high quality (with the residual gaps and errors mostly falling within repetitive elements) and reflects 99% of the total sequence. Importantly, comparative-grade sequence finishing requires ∼40-fold less reagents and ∼10-fold less personnel effort compared to the generation of near-perfect finished sequence, such as that produced for the human genome. Although applied here to finishing sequence derived from individual bacterial artificial chromosome (BAC) clones, one could envision establishing routines for refining sequences emanating from whole-genome shotgun sequencing projects to a similar quality level. Our experience to date demonstrates that comparative-grade sequence finishing represents a practical and affordable option for sequence refinement en route to comparative analyses.

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Comparative genomic sequence analysis of the human and mouse cystic fibrosis transmembrane conductance regulator genes

Cited by 64 publications

References 67 publications

Animal models of chronic lung infection with Pseudomonas aeruginosa: useful tools for cystic fibrosis studies

Animal models of chronic lung infection with Pseudomonas aeruginosa: useful tools for cystic fibrosis studies

The Phenotypic Consequences of CFTR Mutations

An intermediate grade of finished genomic sequence suitable for comparative analyses

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