CFTR gene

Examples of CFTR gene in the following topics:

• Cystic Fibrosis

  • CF is caused by a mutation in the gene for the protein cystic fibrosis transmembrane conductance regulator (CFTR).
  • Ideally, gene therapy attempts to place a normal copy of the CFTR gene into affected cells.
  • Transferring the normal CFTR gene into the affected epithelium cells would result in the production of functional CFTR in all target cells, without adverse reactions or an inflammation response.
  • Studies have shown that to prevent the lung manifestations of cystic fibrosis, only 5–10% the normal amount of CFTR gene expression is needed.
  • Finally, a number of small molecules that aim at compensating various mutations of the CFTR gene are under development.

• Direct Gene Activation and the Second-Messenger System

  • Nuclear receptors function as transcription factors because they can bind to DNA and regulate gene expression.
  • Receptors can either directly influence gene expression and thus cell activity, or induce a secondary signalling cascade which will in turn influence cell activity.
  • Receptors which can directly influence gene expression are termed nuclear receptors.
  • Nuclear receptors can bind directly to DNA to regulate specific gene expression and are, therefore, classified as transcription factors.
  • Distinguish between the hormone mechanisms of direct gene activation and second-messenger system

• Congenital Defects

  • However, children with two genes for achondroplasia (one from each parent) have an even more severe skeletal disorder.
  • Genetic diseases may be divided into single-gene defects, multiple-gene disorders, or chromosomal defects.
  • Single-gene defects may arise from abnormalities of both copies of an autosomal gene (a recessive disorder) or of only one of the two copies (a dominant disorder).
  • Some conditions result from deletions or abnormalities of a few genes located contiguously on a chromosome.
  • Most of these are single gene defects, usually heritable.

• Antibodies: Classes and Affinity Maturation

  • The region (locus) of a chromosome that encodes an antibody is large and contains several distinct genes for each antibody domain— in humans the locus containing heavy chain genes (IGH) is found on chromosome 14, and the loci containing lambda and kappa light chain genes (IGL and IGK) are found on chromosomes 22 and 2.
  • The heavy chain locus contains about 65 different variable domain genes, all with differing CDRs.
  • Combining these genes with an assortment of genes for other antibody domains generates a large cavalry of antibodies (i.e., a high degree of variability).
  • SHM results in approximately one nucleotide change per variable gene, per cell division.
  • This process results in an immunoglobulin gene that encodes an antibody of a different isotype.

• Overview of Cancer

  • At the genetic level, cell proliferation can either be promoted or repressed via the expression of key genes; with alteration of these genes, expression or function via mutation, as induced by the factors discussed above, result in dysregulated proliferation.
  • Oncogenes are genes that promote cell growth and reproduction, such as the gene MYC.
  • Tumor suppressor genes are genes that inhibit cell division and survival, such as the TP53 gene.
  • Typically, changes in multiple genes are required to transform a normal cell into a cancer cell.
  • Cancer develops due to mutations in several key genes that control cell proliferation and survival.

• Autoimmune Diseases

  • In contrast to classical inherited genetic diseases, like sickle cell anemia, autoimmune diseases are not caused by the defect of a single gene, but by the dysfunction of the complex interaction of a group of genes.
  • There are over 50 publications that list gene variants that are associated with a certain autoimmune disease.
  • Interestingly, a lot of these genes are located in the same regions on the chromosomes, the so called susceptibility regions.
  • However, defects of one or more of these genes do not cause an autoimmune disease, but only predispose a person for an autoimmune disease.
  • Studies with monogenetic twins have revealed that genetic influences only account for 25–40% of the disease risk making gene-environment interactions or environmental influences the predominant factors.

• Phenylketonuria (PKU)

  • Phenylketonuria (PKU) is an autosomal recessive metabolic genetic disorder due to a mutation in the phenylalanine hydroxylasegene gene.
  • The PAH gene is located on chromosome 12 in the bands 12q22-q24.1.
  • More than 400 disease-causing mutations have been found in the PAH gene.
  • Because PKU is an autosomal recessive genetic disorder, both parents must have at least one mutated allele of the PAH gene.
  • Tetrahydrobiopterin deficiency can be caused by defects in four different genes.

• Vitiligo

  • Although there is no significant proof or evidence, many doctors believe that it can be caused by defects in several different genes.
  • Variations in genes that are part of the immune system or part of melanocytes have both been associated with vitiligo.
  • These genes are also associated with other autoimmune disorders, adding weight to the theory.

• Albinism

  • It results from inheritance of recessive gene alleles and is known to affect all vertebrates.
  • Most forms of albinism are the result of the biological inheritance of genetically recessive alleles (genes) passed from both parents of an individual, though some rare forms are inherited from only one parent.
  • However, because organisms can be carriers of genes for albinism without exhibiting any traits, albinistic offspring can be produced by two non-albinistic parents.

• Polycystic Kidney Disease

  • There are three genetic mutations in the PKD-1, PKD-2, and PKD3 gene with similar phenotypical presentations.
  • Gene PKD-1 is located on chromosome 16, and codes for a protein involved in regulation of cell cycle and intracellular calcium transport in epithelial cells; it is responsible for 85% of the cases of ADPKD.
  • PKD3 recently appeared in research papers as a postulated 3rd gene.
  • Under the function of gene defect, epithelial cells of renal tubule turn into epithelial cells of cyst wall after phenotype change and begin to have the function of secreting cyst fluid, which leads to continuous cysts enlargement.