Mutations in different genes

The most informative genetic studies were performed on cells containing two copies of the lac operon with point mutations in different genes. Partial diploids (merodiploids) of this sort are constructed by mating experiments in which a second copy of the lac region is incorporated into the test cell by mating. For this purpose the F factor plasmid is a... 

McLellan A, Phillips HA, Rittey C, Kirkpatrick M, Mulley JC, Goudie D, Stephenson JB, Tolmie J, Scheffer IE, Berkovic SF, Zuberi SM (2003) Phenotypic comparison of two Scottish families with mutations in different genes causing autosomal dominant nocturnal frontal lobe epilepsy. Epilepsia 44 613-617... 

Inherited sensory neuropathies caused by mutations in different genes (HSN l-V)... 

Complementation analysis determines whether recessive mutations are in the same or different genes. Complementation tests in yeast are performed by mating haploid a and a cells carrying different recessive mutations to produce diploid cells. In the analysis of cdc mutations, pairs of different haploid temperature-sensitive cdc strains were systematically mated and the resulting diploids tested for growth at the permissive and nonpermissive temperatures. In this hypothetical example, the cdcX and cdcY mutants complement each other and thus have mutations in different genes, whereas the cdcX and cdcZ mutants have mutations in the same gene. 

Figure 49-10. Simplified scheme of the causation of malignant hyperthermia (MIM 145600). At least 17 different point mutations have been detected in the RYRl gene, some of which are associated with central core disease (MIM 117000). It is estimated that at least 50% of families with members who have malignant hyperthermia are linked to the RYRl gene. Some individuals with mutations in the gene encoding DHPR have also been detected it is possible that mutations in other genes for proteins involved in certain aspects of muscle metabolism will also be found.

Although African Americans and whites share many of the same genetic susceptibilities, some racial differences in the incidence or significance of certain disease predictions may exist. In some cases, African Americans may have a risk that whites do not. For example, researchers have recently found that a mutation in the gene coding for a protein essential for blood clotting... 

Mutation screening methods involve testing for specific (previously selected) mutations in a gene. This approach is relatively inexpensive and may be useful for disorders that are caused by one or few common mutations. It is important to take the origin of the patient into consideration, since the frequency of mutations differs markedly between populations. As an example for such a method we discuss restriction enzyme analysis in more detail in this chapter. 

Antenatal diagnosis of PKU Classic PKU is a family of diseases caused by any of forty or more different mutations in the gene that codes for phenylalanine hydroxylase PAH). The frequency of any given mutation varies among populations, and the disease is often doubly heterozygous, that is, the PAH gene has a different mutation in each allele. Despite this complexity, the majority of PKU cases in most populations are caused by a small number of mutations (six to ten). A fetus can be tested in vitro to determine if it carries a PKU mutation (see p. 458). 

The role of the initial binding RNA in Figure 6.1 is now fulfilled by aminoacyl-synthetases which were selected from a number of proteins of suitable activity. An inordinately large number of this type of structural motif is found in different genes which supports the basic concept of function selection (13) as opposed to the development of function by targeted mutations. 

---