Mutations disease

RyR2 mutations Disease References RyR2 mutations Disease References... 

Stmctural defects at the receptor level are determinant for a number of receptor diseases. In nephrogenic diabetes insipidus, where patients void large volumes of dilute urine even in the presence of vasopressin (antidiuretic hormone) (105), the disease is linked to mutations in three discrete regions of the G-protein-linked vasopressin (V2) receptor (106,107). 

Defects in the LDL receptor have been particularly well explored as a basis of the disease familial hypercholesterolemia (93,111). A number of defects that collectively impair LDL receptor trafficking, binding, or deUvery underHe this disease where LDL and semm cholesterol rise to levels that mediate early cardiovascular mortaUty. Studies of the population distribution of this defect can determine the source of the original mutation. Thus, in Quebec, about 60% of the individuals suffering from familial hypercholesterolemia have a particular 10-kdobase deletion mutation in the LDL gene (112). This may have arisen from an original founder of the French Canadian settiement in the seventeenth century. 

Cystic fibrosis, a disease of the Caucasian population, is associated with defective CL regulation and is essentially a disorder of epithehal cells (113,114). The defect arises at several levels in the CL ion transporter, ie, the cystic fibrosis transmembrane regulation (CFTR), and is associated with defective CL transport and defective processing, whereby the protein is not correctiy incorporated into the cell membrane. The most common mutation, affecting approximately 60% of patients, is termed F 608 and designates the loss of phenylalanine at this position. This mutation appears to be at least 50,000 years old, which suggests that its survival may have had evolutionary significance (115). 

S Greenland. Probability logic and probability induction. Epidemiology 9 322-332, 1998. GM Petersen, G Parmigiam, D Thomas. Missense mutations in disease genes A Bayesian approach to evaluate causality. Am J Hum Genet. 62 1516-1524, 1998. 

Sickle-cell anemia is the classic example of an inherited disease that is caused by a change in a protein s amino acid sequence. Linus Pauling proposed in 1949 that it was caused by a defect in the hemoglobin molecule he thus coined the term molecular disease. Seven years later Vernon Ingram showed that the disease was caused by a single mutation, a change in residue 6 of the P chain of hemoglobin from Glu to Val. 

We thus have here a case where a mutation on the surface of the globin fold, replacing a hydrophilic residue with a hydrophobic one, changes important properties of the molecule and produces a lethal disease. Why has the... 

A mutagen is a chemical that can induce alterations in the DNA. Mutations occurring in germ cells are inheritable and may lead to genetic diseases. If mutations take place in somatic cells, carcinogenesis may be initiated. 

Organ specific autoimmune disease Constitutively activating somatic mutation in TSH... 

Knocking out genes and identification of mutations in the human genes provide information on the role of AQPs in normal physiology. The lack of some AQPs directly results in a disease phenotype, while the physiological role of many becomes clear when the putative function is challenged. 

Mutations in two genes directly lead to a disease. Mutations in the AQPO gene lead to dominantly inherited cataract. Single amino acid substitution in the AQPO gene in both mice and humans result in proteins with impaired trafficking to the plasma membrane and cataract formation, due to loss of the integrity of the lens. 

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