Related Experiment Video
Updated: May 22, 2026
09:34
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Functional analysis of nonsynonymous single nucleotide polymorphisms in human SLC26A9
An-Ping Chen1, Min-Hwang Chang, Michael F Romero
1Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, 200 First St SW, Rochester, Minnesota, USA.
Human Mutation
|May 1, 2012
Summary
Investigating SLC26A9 gene variants reveals altered anion transport functions. These genetic changes impact Slc26a9 protein activity and expression, potentially influencing diseases like cystic fibrosis.
Area of Science:
- Molecular Biology
- Physiology
- Genetics
Background:
- Slc26 anion transporters are vital for Cl(-) absorption and HCO(3)(-) secretion.
- Mutations in Slc26 proteins are linked to various diseases.
- Slc26a9, a Cl(-) channel and Cl(-)--HCO(3)(-) exchanger, interacts with CFTR; Slc26a9(-/-) mice show reduced gastric acid secretion.
Purpose of the Study:
- To investigate the functional consequences of nonsynonymous coding single nucleotide polymorphisms (cSNPs) in the human SLC26A9 gene.
- To determine how specific SLC26A9 cSNPs affect its channel and exchanger activities.
- To explore the potential pathophysiological implications of SLC26A9 genetic variations.
Main Methods:
- Utilized two-electrode voltage-clamp electrophysiology to measure ion transport.
- Employed anion-selective electrodes to quantify transport rates.
- Analyzed eight documented SLC26A9 cSNPs: Y70N, T127N, I384T, R575W, P606L, V622L, V744M, and H748R.
Main Results:
- The Y70N variant exhibited increased channel activity and Cl(-)--HCO(3)(-) exchange.
- The T127N variant showed reduced halide currents, except for SCN(-).
- V622L and V744M variants decreased plasma membrane expression and reduced whole-cell currents, with V622L transport diminished by approximately 50%.
Conclusions:
- SLC26A9 polymorphisms result in diverse functional modifications, including altered activity and protein expression.
- These functional changes could contribute to a range of diseases.
- Understanding SLC26A9 genetics is crucial for comprehending and potentially managing diseases associated with its mutations, such as cystic fibrosis.
Related Concept Videos
01:16Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters
The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
02:26Comparing Copy Number Variations and SNPs
Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
01:05Single Nucleotide Polymorphisms-SNPs
A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
01:27Principles of Pharmacogenetics: Types of Genetic Variants
The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
01:11Genome-wide Association Studies-GWAS
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
01:29Pharmacogenomics: Identification of New Drug Targets
Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...