Dominant mutation

MODY is a type of non-insulin-dependent diabetes mellitus caused by rare autosomal-dominant mutations. Presently there are six known forms of the disease which are all due to ineffective insulin production or... 

Research on radiation-induced recessive lethal mutations — the predominant type of radiation-induced mutation — and dominant mutation systems (Sankaranarayanan 1991c)... 

Autosomal dominant mutations in COL1A1 or COL1A2 The majority result from dominant mutations in COL1A1 or C0L1A2... 

X-Iinked dominant inheritance (choice D) is excluded because affected males can transmit X-linked dominant mutations to their daughters. 

Down syndrome (choice D) typically is the result of a new mutation. When it is transmitted by an affected female, it acts like a dominant mutation and thus would not be affected by consanguinity. 

If a mutation is lethal, a homozygote will not survive and will be lost in an early (and usually undetected) spontaneous abortion. Healthy individuals carry as many as ten lethal recessive mutations as well as at least 3-5 autosomal recessive mutations of a seriously harmful type. Harmful dominant mutations are also frequent in the population. These include an elevated lipoprotein content of the blood and an elevated cholesterol level which are linked to early heart disease. 

Two types of inherited disorders caused by mutations of genes related to BH4 are known. Autosomal dominant mutations in the GCH gene are causative for DOPA-responsive dystonia (DRD) [157,158]. Malignant hyperphenylalaninemia or atypical phenylketonuria (PKU) is caused by recessive mutations of genes encoding BH4-biosynthetic or recycling enzymes [159]. 

Seburn, K. L., Nangle, L. A., Cox, G. A., Schimmel, P. and Burgess, R. W. (2006) An active dominant mutation of glycyl-tRNA synthetase causes neuropathy in a Charcot-Marie-Tooth 2D mouse model. Neuron 51, 715-726. 

By this approach, positive clones are expected to arise from overexpression of wild-type genes conferring resistance or from frans-dominant mutations giving a mutant (resistant) phenotype (14). To identify loss-of-function recessive mutations the method should be reversed P-RES resistant clones should be transformed with a genomic library constructed with the DNA of the wild-type HB101, and clones with restored peptide susceptibility analyzed. 

Chromosomes occur in pairs of each pair, one member is contributed by the mother and one by the father. Therefore, genes also occur in pairs. A gene that produces its characteristic effect (its phenotype) when only one of its type is present is dominant. If two are required, the gene is recessive. If a mutant gene is recessive, hundreds of generations may pass before it chances to encounter a partner like itself, which permits its effect to be expressed. In contrast, a dominant mutation may be expressed in the generation immediately after it occurs. 

Severe dominant mutations exert their main effects in the first few generations, in contrast with recessive mutations, which are spread out over enormous periods (as are genes with very mild effects). Thus, it is much more feasible to estimate the consequences of dominant mutations than of those whose effects are greatly diluted by time and by space (because of migration, a mutation may be expressed in a different part of the world from that in which it occurred). 

About one-fifth of human dominant diseases listed in McKusick s compendium279 have skeletal effects, but the true proportion of all dominant mutations having skeletal effects is probably closer to one-tenth.1 73 About half the dominant skeletal mutations in mice have severe... 

Chapter 6 described methods for estimating the increase in the rate of dominant mutations from environmental chemicals on the basis of data on skeletal defects and cataracts in the mouse and estimates of the fraction of all severe human diseases that affect the skeleton or cause cataracts. Thus, we are in a position to make a tenuous estimate of the percentage by which the rate of human dominant mutation would be increased by some environmental mutagen. If penetrance is complete, the mutant genes will be expressed in the next and in ensuing generations until (as described in Chapter 3) they are eliminated by a decrease in the survival or fertility of their carriers. 

UNSCEAR473 based its quantitative risk estimates mainly on severe dominant diseases. Recessive and complexly inherited diseases were regarded as too poorly understood and too diluted by time to be considered. The BEIR reports302 303 included disease of complex inheritance by making arbitrary assumptions about the extent to which the incidence is mutationally caused and about the time distribution. We agree with the policy of placing major emphasis on severe dominant mutations, but will treat the subject in a more systematic way. 

In one strain of mice, treating the parents with radiation or urethane produced an increase in cancers, primarily in the lung, in the progeny. These were inherited as though they were dominant mutations with about 40% penetrance. Whether these results can be generalized to other species, or even to other strains of mice, will not be clear until more experiments are done.325... 

Unfortunately, the most important discrepancy between the Irish and Canadian studies is in the dominant category— probably the most important, in view of the prompt egression of dominant mutations. One cause of disagreement is that the earlier Stevenson study classified as... 

For estimating the risk from dominant phenotypes, the Committee favors a dominant-mutation test in mice as most relevant to the human situation. If the risk is primarily chromosomal breakage, the heritable-translocation test is preferred. 

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