Genes mutations encoding proteins

To date, the genetic origin of low HDL cholesterol has been unraveled only to a minor degree. Family studies in humans have identified at least 30 quantitative trait loci that cover almost all chromosomes. Most known mutations underlying monogenic forms of HDL deficiency have been found in genes that encode proteins involved in the formation, maturation, and catabolism of HDL. 

There is increasing evidence that iron is involved in several neurodegenera-tive diseases. Conditions such as neuroferritinopathy and Friedreich ataxia are associated with mutations in genes that encode proteins that are involved in iron metabolism. As the brain ages, iron accumulates in regions that are affected in AD and PD. High concentrations of reactive iron can increase... 

I 3. The answer is a. (Murray, pp 412-434. Scriver, pp 769-784. Sack, pp 3-29. Wilson, pp 99—121.) One ol the most common types of inherited cancers is nonpolyposis colon cancer [HNPCC (114500)]. Most cases are associated with mutations of either of two genes that encode proteins critical in the surveillance of mismatches. Mismatches are due to copying errors leading to one- to five-base unmatched pieces of DNA. Two- to five-base-long unmatched bases form miniloops. Normally, specific proteins survey newly formed DNA between adenine methylated bases within a GATC sequence. 

Synthetic lethal mutations also can reveal nonessential genes whose encoded proteins function in redundant pathways for producing an essential cell component. As depicted in Figure 9-9c, if either pathway alone is inactivated by a mutation, the other pathway will be able to supply the needed product. However, if both pathways are inactivated at the same time, the essential product cannot be synthesized, and the double mutants will be nonviable. 

Table 46-9. Some disorders due to mutations in genes encoding proteins involved in intracellular membrane transport. ...

Various Disorders Result From Mutations in Genes Encoding Proteins Involved in Intracellular Transport... 

Gleeson JG, Allen KM, Fox JW et al 1998 doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein. Cell 92 63-72... 

Adrenoleukodystrophy is an X-linked dysmyelinative disorder caused by mutations in the ABCD1 gene, which encodes the peroxisomal integral membrane ALD protein, a member of the ATP binding cassette transporter family. These mutations result in impaired clearance of plasma very-long-chain fatty acids. Affected males may present with symmetrical distal axonal polyneuropathy, adrenocortical insufficiency or CNS demyelination, while occasional heterozygous women demonstrate deficits suggestive of multiple sclerosis [56]. Manipulation of dietary fatty acid intake has some minimal therapeutic effect, while bone marrow transplantation has diminished deficits in a few patients. (See in Ch. 41.)... 

Mutations in one nuclear gene (ATP12), encoding an ATPase assembly protein, have been associated with complex V deficiency in an infant with congenital lactic acidosis and a rapidly fatal disorder affecting brain, liver, heart, and muscle [19]. 

Inhibition of the lipid modification cascade provides an alternative way to block aberrant signaling pathways and that opportunity can be exploited in anticancer therapy. As part of the growth factor, signaling of the false activation is transmitted by the mutated ras gene encoded proteins (Ras) and ultimately leads to uncontrolled cell growth. These typical GTP binding proteins are also subject to membrane anchoring and the biosynthesis of those Ras proteins can be blocked at the posttranslational prenylation step. 

CF is caused by the absence of a protein called cystic fibrosis transmembrane conductance regulator (CFTR). This protein is required for the transport of chloride ions across cell membranes. On the molecular level, there is a mutation in the gene that encodes for CFTR. As a result, CFTR cannot be processed properly by the cell and is unable to reach the exocrine glands to assume its transport function. 

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