Application of DETECTER, an evolutionary genomic tool to analyze genetic variation, to the cystic fibrosis gene family

BMC Genomics
Eric A GaucherSteven A Benner

Abstract

The medical community requires computational tools that distinguish missense genetic differences having phenotypic impact within the vast number of sense mutations that do not. Tools that do this will become increasingly important for those seeking to use human genome sequence data to predict disease, make prognoses, and customize therapy to individual patients. An approach, termed DETECTER, is proposed to identify sites in a protein sequence where amino acid replacements are likely to have a significant effect on phenotype, including causing genetic disease. This approach uses a model-dependent tool to estimate the normalized replacement rate at individual sites in a protein sequence, based on a history of those sites extracted from an evolutionary analysis of the corresponding protein family. This tool identifies sites that have higher-than-average, average, or lower-than-average rates of change in the lineage leading to the sequence in the population of interest. The rates are then combined with sequence data to determine the likelihoods that particular amino acids were present at individual sites in the evolutionary history of the gene family. These likelihoods are used to predict whether any specific amino acid replacement...Continue Reading

References

Nov 1, 1979·Hoppe-Seyler's Zeitschrift für physiologische Chemie·G C SteffensG Buse
Jun 1, 1992·Computer Applications in the Biosciences : CABIOS·D T JonesJ M Thornton
Jan 20, 1967·Science·W M Fitch, E Margoliash
Jan 26, 1996·Science·U M ChandrasekharanA Husain
Feb 1, 1996·Molecular Biology and Evolution·R L GoodwinF G Berger
Mar 29, 1996·Journal of Molecular Biology·O LichtargeF E Cohen
Jun 25, 1996·Proceedings of the National Academy of Sciences of the United States of America·S C LiC M Deber
Sep 1, 1997·Nucleic Acids Research·S F AltschulD J Lipman
Nov 21, 1997·Computer Applications in the Biosciences : CABIOS·Z Yang
Mar 7, 2001·Human Molecular Genetics·S SunyaevP Bork
May 5, 2001·Genome Research·P C Ng, S Henikoff
Jun 28, 2001·Nature Structural Biology·A G TherienC M Deber
Mar 5, 2002·Genome Research·Pauline C Ng, Steven Henikoff
Jun 11, 2002·Journal of Molecular Biology·K Fukami-KobayashiS A Benner
Jun 19, 2002·Trends in Biochemical Sciences·Eric A GaucherSteven A Benner
Aug 30, 2002·Molecular Biology and Evolution·Belinda S W ChangThomas P Sakmar
Aug 31, 2002·Nucleic Acids Research·Vasily RamenskyShamil Sunyaev
Jan 23, 2003·Biopolymers·Anthony W PartridgeCharles M Deber
Jun 26, 2003·Nucleic Acids Research·Pauline C Ng, Steven Henikoff
Jul 2, 2003·Molecular Biology and Evolution·Simonetta GribaldoHervé Philippe
Aug 9, 2003·Nature Reviews. Drug Discovery·David B Searls
May 15, 2004·Nature Reviews. Genetics·Joseph W Thornton
Aug 19, 2004·BMC Biology·Eric A GaucherSteven A Benner

❮ Previous
Next ❯

Citations

Oct 25, 2011·Applied and Environmental Microbiology·Ian K BlabyEudes de Crécy
Feb 8, 2007·American Journal of Rhinology·Bradford A WoodworthRodney J Schlosser

❮ Previous
Next ❯

Software Mentioned

BLAST
PAUP
MasterCatalog
Perl script
PAML
SIFT
POLYPHEN
ClustalW
DETECTER
PSI

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

IEEE Engineering in Medicine and Biology Magazine : the Quarterly Magazine of the Engineering in Medicine & Biology Society
C C CollinsA Jamplosky
Enfermedades infecciosas y microbiología clínica
Ramón TeiraRamón Cisterna
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Mi Ah HanYoung-Woo Kim
© 2021 Meta ULC. All rights reserved