Mendelian patterns of inheritance

Alzheimer s disease exists in two major forms, the so-called early and late onset types. The former follows typical Mendelian inheritance while the latter shows a more complex, non-Mendelian, pattern of inheritance. The early onset form of the disease has permitted the identification of several genes which are causally related to the condition. 

A few strokes are clearly familial with a simple Mendelian pattern of inheritance of the underlying cause (Table 3.2). Some of these genetic causes of stroke are described below ... 

About 10% of ALS cases are familial (FALS), with a Mendelian pattern of inheritance. About 20% of these cases are associated with mutations in the copper/zinc superoxide dismutase 1 gene (SODl) (Valdmanis and Rouleau 2008). To date, more than 100 different mutations within all exons of the SODl gene and its introns have been identified as being involved in the development of chromosome 21q-linked... 

The rules of segregation of alleles originally defined by Gregor Mendel explained mnch of the phenomena associated with inheritance and have been dogmatically applied in the field of genetics. However, there are situations in which the rules of Mendelian inheritance cannot explain observed phenomena. A variety of molecular mechanisms have been identified that explain certain phenomena that are not easily explained by traditional Mendelian patterns of inheritance. These non-Mendelian mechanisms differ on a molecnlar basis, but can be described as a group by the term nontraditional mechanisms of inheritance or nontraditional inheritance. Stated simply, nontraditional inheritance refers to the pattern of inheritance of a trait or phenotype that occurs predictably, recurrently, and in some cases familiaUy, but does not follow the rules of typical Mendelian antosomal or sex chromosome inheritance. 

Within a population there is a proportion of individuals who are predisposed to develop cancer, either as an apparently sporadic disease or in response to an environmental challenge, such as exposure to tobacco smoke or ionising radiation. The abnormally high frequency of some tumor types within related members of large famihes provided evidence that cancer is, in some circumstances, a heritable disease. Genetic linkage studies of these famihes has revealed that a number of these cancer syndromes occur as simple Mendelian traits, usuaUy with a highly penetrant dominant pattern of inheritance. 

A disease whose pattern of familial aggregation differs from that expected fi om the Mendelian inheritance of a single genetic defect. 

Mitochondria are unique organelles in that they contain their own DNA (mtDNA), which, in addition to ribosomal RN A (rRNA) and transfer RN A (tRNA)-coding sequences, also encodes 13 polypeptides which are components of complexes I, III, IV, and V (Anderson et al., 1981). This fact has important implications for both the genetics and the etiology of the respiratory chain disorders. Since mtDNA is maternally-inherited, a defect of a respiratory complex due to a mtDNA deletion would be expected to show a pattern of maternal transmission. However the situation is complicated by the fact that the majority of the polypeptide subunits of complexes I, III, IV, and V, and all subunits of complex II, are encoded by nuclear DNA. A defect in a nuclear-coded subunit of one of the respiratory complexes would be expected to show classic Mendelian inheritance. A further complication exists in that it is now established that some respiratory chain disorders result from defects of communication between nuclear and mitochondrial genomes (Zeviani et al., 1989). Since many mitochondrial proteins are synthesized in the cytosol and require a sophisticated system of posttranslational processing for transport and assembly, it is apparent that a diversity of genetic errors is to be expected. 

Not all hereditary traits follow the Mendelian patterns expected for chromosomal genes. Some are inherited directly from the maternal cell because their genes are carried in the cytoplasm rather than the nucleus. There are three known locations for cytoplasmic genes the mitochondria, the chloroplasts, and certain other membrane-associated sites.285 286 An example of the last is found in "killer" strains of yeast. Cells with the killer trait release a toxin that kills sensitive cells but are themselves immune. The genes are carried in double-stranded RNA rather than DNA, but are otherwise somewhat analogous to the colicin factors of enteric bacteria (Box 8-D). Similar particles (kfactors) are found in Paramecium.287... 

Data on asthma are a good example of the complexities of interacting genes, diseases, and drugs. First, there is no universally accepted definition of asthma. Twin studies suggest that asthma is to 0.72%-0.8% a genetic disease,but inheritance does not follow a clear Mendelian pattern, and environmental factors modulate the clinical expression. " Thus, asthma is multifactorial. Disease expression is influenced by interactions between multiple major and minor genes, and modulated by environmental factors. " ... 

Inheritance of HLA characteristics follows a simple Mendelian pattern. The genetic loci controlling the various HLA subregions are contained within the major histocompatibility complex on chromosome 6 (Fig. 1). Each individual inherits one chromosome 6 from one parent and one from the other parent, each chromosome coding for one HLA-A gene, one HLA-B gene, one HLA-C gene, and so on. The HLA-A locus will be occupied by one of the alleles listed in Table 1 under the column headed HLA-A , the HLA-B locus will be occupied by one of the alleles listed under HLA-B , and so on. 

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