Genetic diseases phenotypic expression

If only one copy of an allele is required for its phenotypic expression, the allele is dominant (i.e., it is observable in the heterozygous state). If two copies of the allele are required for its expression (i.e., the disease phenotype is observable only in the homozygous state), it is recessive. The expression of the recessive alleie is thus hidden in the heterozygote. The terms dominant and recessive provide a convenient classification of genetic diseases, as seen below. If two different alleles are both phenotypicaUy expressed in a heterozygous genotype, the alleles are said to be codominant. 

Most genetic diseases vary in the degree of phenotypic expression some individuals may be severely affected, whereas others are more mildly affected. This can be the result of several factors ... 

Goldberg YP, Kalchman MA, Metzler M, et al (1996) Absence of disease phenotype and intergenerational stability of the CAG repeat in transgenic mice expressing the human Huntington disease transcript. Hum Mol Genet 5 177-185... 

Interestingly, a small subset of patients with major psychoses, but without ataxia, appears to possess the SCA8 mutation (Vincent et al., 2000). Thus, additional genetic and/or environmental factors may play an important role in the expression of SCA 8 ataxia disease phenotype (Ikeda et al., 2004) or psychoses (Vincent et al.,... 

Leber hereditary optic neuropathy (LHON) is the most common mitochondrial disease and the first linked to maternal inheritance through a mutation in the mtDNA. LHON is characterized by bilateral subacute loss of central vision caused by focal degeneration of the retinal ganglion cell layer and of the optic nerve. After initial symptoms, both eyes are usually affected within 6 months. Approximately 50% to 60% of males and only 8% to 32% of females who possess the mtDNA mutation will actually develop this optic neuropathy. Nuclear-encoded factors that affect mtDNA expression, mtDNA products, or mitochondrial metabolism may modify the phenotypic expression of LHON. Genetic coimseling in LHON is complicated in that the amount of mutant mtDNA transmitted by heteroplasmic females cannot be predicted, and testing cannot predict which individuals will develop visual symptoms. ... 

Thus, one can conclude that moral forces, faith, guilt feelings, and obedience to commandments and laws result from both genetic and environmental fertors. Molecular medicine makes it possible to examine the phenotypic expression of molecular processes in the brain that interact with these forces. Molecular processes help define one s personality. These can be characterized quantitatively as deviations from normal molecular processes. Disease can be defined in terms of abnormalities in one or more regional biochemical processes. 

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