Mutation spectrum

Non-Jewish. Because Ashkenazi Jews tend to partner with others from their ethnic group, the mutation spectrum for common hereditary disease is often confined within that population. Mating tendencies cause certain alleles to become more prevalent within the inbred population than in the country as a whole. Therefore, mutation coverage and risk-reduction statistics are specific for a particular ethnicity. As a consequence, an Ashkenazi Jewish individual with a negative CF test by DNA and no family history has a significantly diminished risk of being a carrier (1/801) compared with a Caucasian non-Jew (1/241) with the same assay result. 

It is necessary to compare the mutation spectrum induced by ion beams with that by the low-LET radiation to figure out a special feature of ion beams as an effective mutagen. Mutation... 

Recently, mutation spectrum of flower color and flower shape of carnation was also investigated by Okamura et al. [108]. In the carnation variety Vital (spray-type, cherry pink flowers with frilly petals) tested, flower color mutants such as pink, white, and red were obtained by X-ray irradiation, whereas the color spectrum of the mutants obtained by carbon ion irradiation was wide such as pink, light pink, salmon, red, yellow, and complex and striped types. Furthermore, many kinds of round shape of petals were induced in addition to flower colors. These indicate that ion beams can induce novel flower color and shape with high frequency. 

Table 3 Mutation Spectrum of Flower Color in Chrysanthemum...

Other Plants. As already described in Mutation Spectrum, complex and striped types of flower color have been obtained in chrysanthemum. A higher mutation frequency... 

The large number of known sequences of the p53 gene from tumor patients was particularly valuable for interpretation of the crystal structure since a spectrum could be assembled for p53 mutation in association with tumor formation. The mutation spectrum shown in Fig. 14.9 shows hotspots , positions at which p53 mutations are seen particularly frequently in tumor patients. 

Comparison of the mutation spectrum with the structure of the p53-DNA complex indicates that the positions of frequent mutations coincide with the conserved structu-... 

Fig. 14.9. Mutation spectrum of the p53 protein in tumors. The linear strnctnre is shown of p53 and the frequency of mutations found in tumors. The black bars indicate the approximate position and the relative frequency of the p53 mutations. The frequency of mutations in the region of the DNA binding domain is of note. The sites of the most frequent mutations coincide with positions of the p53 protein that are directly involved in interactions with the DNA sequence (see Fig. 14.8). According to Cho et al., (1994), with permission.

Overall, comparison of the structure data with the natural mutation spectrum of p53 shows that specific DNA binding is closely associated with the function as a tumor suppressor. A disruption of specific DNA binding apparently has serious effects on the tumor suppressing fimction of p53. 

Mandey SH, Schneiders MS, et al. (2006) Mutational spectrum and genotype-phenotype correlations in mevalonate kinase deficiency. Hum Mutat 27 796-802... 

In a study by Sisk et al. (1994), male B6C3Fj lad transgenic mice were exposed by inhalation to 0, 62.5, 625 or 1250 ppm [0, 138, 1380 or 2760 mg/m ] butadiene for four weeks (6 h per day, five days per week). Animals were killed 14 days after the last exposure and lad mutants were recovered from the DNA according to established protocols. A 2.5- and 3-fold increase in the lad mutant frequency was observed in the bone marrow of mice exposed to 625 or 1250 ppm butadiene, respectively, compared with air-exposed control mice. DNA sequence analysis of lad mutants recovered from the bone marrow of mice exposed to 625 ppm butadiene demonstrated that there was a shift in the spectrum of base substitution mutations at A T base pairs in butadiene-exposed mice (6/26, 23%), compared to air control mice (2/45, 4%). Recio and Meyer (1995) examined the lad mutational spectrum in the bone marrow of mice exposed to 1250 ppm butadiene in the above study. DNA sequence analysis of lad mutants revealed an increase in mutations at A T base pairs (9/49, 20%) similar to that observed by Sisk et al. (1994). 

Recio et al. (1998) also examined the lad mutagenicity and mutational spectrum in the spleen of mice exposed to butadiene in the above study. The authors reported three-and four-fold increases in the lad mutant frequency in mice exposed to 625 or 1250 ppm butadiene, respectively, compared with air control mice. DNA sequence analysis of lad mutants recovered from the spleen of mice exposed to 1250 ppm butadiene once again revealed an increase in mutations at A T base pairs (10/57, 18%) in butadiene-exposed mice compared with air control mice (3/41, 7%). In addition, an increased frequency of... 

G CMA T transitions occurred at non-5 CpG-3 sites in butadiene-exposed mice. The increased frequency of specific mutations at G C base pairs was not observed in bone marrow from the same animals there seem therefore to be tissue-specific differences in the butadiene mutational spectrum. 

Redo, L., Meyer, K.G., Pluta, L.J., Moss, O.R. Saronko, C. (1996) Assessment of 1,3-butadiene mutagenicity in the bone marrow of B6C3F1 lad transgenic mice (big blued A review of mutational spectrum and lad mutant frequency after a 5-day 625 ppm 1,3-butadiene exposure. Environ, mol. Mutag., 28, 424-429... 

Graves, R.J., Trueman, P, Jones, S. Green, T. (1996) DNA sequence analysis of methylene chloride induced HPRT mutations in CHO cells comparison with the mutation spectrum obtained for 1,2-dibromomethane and formaldehyde. Mutagenesis, 11, 229-233... 

Mutazyme operates under optimum PCR conditions and has a different mutational spectrum from standard polymerases Stratagene... 

Smela ME, Currier SS, Bailey EA, Essigman JM. The chemistry and biology of aflatoxin Bi from mutational spectrum to carcinogenesis. Carcinogenesis 2001 22 535-545. 

Tkeshelashvili, L., McBride, T, Spence, K, and Loeb, L. A. (1991). Mutation spectrum of coppe induced DNA damage. J- Sial. Chem. 266, 6401-6406,... 

Campion D, Dumanchin C, Hannequin D, Dubois B, Belliard S, Puel M et al. (1999) Early-onset autosomal dominant Alzheimer disease prevalence, genetic heterogeneity, and mutation spectrum. Am J Hum Genet 65 664-670... 

Trout experimentally exposed to DEN, administered in the diet, also display K-ras mutations82. Seven DEN-induced liver tumors were examined for evidence of K-ras-activating mutations. Of these, a high proportion (6/7) carried a codon 12 GGA to AGA mutation82. The pattern of mutational spectrum for this compound, again,... 

The data accumulated for trout clearly indicates that both the type of inducing compound and the tissue investigated affect the ras mutational spectrum and incidence observed (Table 2). Furthermore, these extensive studies using trout also show that the ras mutational profile differs from that observed in rodent models. There are no reports as yet of p53, or any other tumor suppressor gene, mutations in trout tumor tissue despite readily available methods". While an apparent lack of similarity in mutational profiles may exclude trout as a viable model of mammalian carcinogenesis at the molecular mechanistic level, there still remains the enormous potential by virtue of their induced triploidy status in the development of trout as a model of heritable disease where tumor suppressor genes are implicated. 

Dryja TP, Hahn LB, Cowley GS, Mcgee TL, Berson EL. 1991. Mutation spectrum of the rhodopsin gene among patients with autosomal dominant retinitis pigmentosa. Proc Natl Acad Sci USA 88 9370-9374,... 

Bennett WP, Hussein SP, Vahakangas KH, et al. Molecular epidemiology of human cancer risk Gene-environment interactions andp53 mutations spectrum in human lung cancer. J Pathol 1999 187 8-18. 

Mutation spectrum for some assays (e.g., transgenic models, hprt). 

Comparison of the mutation spectrum with the structure of the p53-DNA complex indicates that the positions of frequent mutations coincide with the conserved structural elements of the DNA-binding domains. It is particularly noticeable that the most frequently mutated position in tumors, namely Arg248, is also the position at which the p53 protein forms a specific contact to recognition sequences. 

Fig. 14.11 Mutation spectrum of the p53 protein in tumors. The linear structure is shown of p53 and the frequency of mutations found in tumors. The black bars indicate the approximate position and the relative frequency of the p53 mutations. The fre-...

Li EE, Culp SJ, Beland FA. 1994. Tumor mutational spectrum in relation to DNA adduct profile in forestomachs of mice fed coal tar or benzo[a]pyrene. Proc Am Assoc Cancer Res 35 148. 

Feki A, Irminger-Finger I (2004) Mutational spectrum of p53 mutations in primary breast and ovarian tumors. Crit Rev Oncol Hematol 52 103-116... 

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