Mutation recessive lethal

DMX, Drosophila melanogaster, sex-linked lethal recessive mutations DIA, DNA strand breaks/cross-links, L1220 mouse leukaemic... 

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. 

In contrast with rare, lethal recessive mutation, extensive studies in Drosophila have shown that the most frequent mutations cure those with only mild effects. In Drosophila, these cure detected as a small reduction in the probability of surviving to adulthood or a small decrease in fertility. Such mutations also are not completely recessive. Therefore, they, like their more drastic recessive counterparts, are eliminated from the population in the heterozygous state. 

Abrahamson, S., F.E. Wurgler, C. DeJongh, and H.U. Meyer. How many loci on the X-chromosome of Drosophila melanogaster can mutate to recessive lethals Environ. Mutagenesis 2 447-453, 1980. 

TK or HPRT forward mutation assays in cultured mammalian ceils Drosophila sex-linked recessive lethal assay... 

D. melanogaster/6 e afy exposure Recessive lethal somatic mutation + Tripathy et al. 1987... 

Insect systems Drosophila melanogaster (sex-linked recessive lethal test) Recessive lethal mutation + Velazquez et al. 1984... 

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

Cystic fibrosis (CF) is the most common potentially lethal autosomal recessive disease among Caucasians. The incidence is estimated to be approximately 1 in 2000 births (Bl). Since it is inherited as an autosomal recessive condition, screening to identify couples at risk has been suggested. However, CF screening is complicated because many mutations of the CF gene exist. Thus, the feasibility of screening a population for carriers of cystic fibrosis gene mutations is primarily dependent upon the frequency of the common mutation in that population. 

Duchenne and Becker muscular dystrophies (DMD and BMD) are X-linked, allelic, neuromuscular diseases. DMD/BMD are characterized by progressive muscular weakness and degeneration of skeletal muscle. DMD is the most common recessive lethal disease, with an incidence of approximately 1 in 3500 newborns, and according to estimates, one-third of the cases are linked with new mutations (M3). Clinical symptoms of the disease appear earlier, by 2 to 3 years of age, in the form of retarded motor development. Progressive symptomatic children show weakness and wasting of muscle and are usually wheelchair bound approximately by the age of 11-12 years. It has been reported that most patients die at about the age of 20 due to pneumonia, which is related to chronic respiratory insufficiency. BMD—being the rarer allelic disorder—has a milder clinical course with slower disease progression. The BMD-affected patients usually survive beyond the age of 30. 

Recessive lethal Forward mutation Forward mutation Forward mutation Forward mutation... 

Zijistra JA, Vogel EW. 1988. The ratio of induced recessive lethals to ring-x loss has prognostic value in terms of functionally of chemical mutagenesis in Drosophila melanogaster. Mutat Res 201 27-38. 

A 30-year-old man is phenotypically normal, but two of his siblings died from infantile Tay-Sachs disease, an autosomal recessive condition that is lethal by the age of five. What is the risk that this man is a heterozygous carrier of the disease-causing mutation ... 

Sex-linked recessive lethal mutations were not produced in Drosophila fed ethanol solution containing 50 ppm 1,2-diphenylhydrazine for 3 days (Yoon et al. 1985). No oral genotoxicity studies of 1,2-diphenylhydrazine in mammals were located. 

Sex-linked recessive Drosophila melanogaster/ lethal mutation feeding... 

Chalhoub, N., Benachenhou, N., Rajapurohitam, V., Pata, M., Perron, M., Frattini, A., Villa, A., and Vacher, J. (2003) Grey-lethal Mutation Induces Severe Malignant Autosomal Recessive Osteopetrosis in Mouse and Human. Nature Medicine, 399-406. 

Pangrazio, A., Poliani, P.E., Megarbane, A., Lefranc, G., Lanino, E., DiRocco, M., Rucci, F., Lucchini, F., Ravanini, M., Facchetti, F., Abinum, M., Vezzoni, P., Villa, A., and Frattini, A. (2006) Mutations in OSTMl (grey-lethal) Define a Particularly Severe Form of Autosomal Recessive Osteopetrosis with Neural Involvement. Journal of Bone and Mineral Research 21, 1098-1105. 

Vogel, E., Blijleven, W.G.H., Kortselius, M.J.H. and Zijlstra, J.A. (1981) Mutagenic activity of 17 coded compounds in the sex-linked recessive lethal test in Drosophila melanogaster, in Progress in Mutation Research, Volume 1 Evaluation of Short-Term Tests Carcinogens (eds F.J. de Serres and J. Ashby), Elsevier, Amsterdam. 

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