Mutations insertion, production

The answer is C. Production of a truncated protein indicates that a mutation has occurred, but this phenomenon may have arisen from a frameshift mutation (insertion or deletion) or by a nonsense mutation. The most likely possibility is a nonsense mutation because sequence analysis of the truncated protein showed that it had normal (wild-type) sequence. Insertion and deletion events often produce a stretch of garbled or abnormal protein sequence at the C-terminal end of the truncated protein arising from out-of-frame translation of the mRNA downstream of the mutation until a stop codon is encountered. 

Single-strand conformation polymorphism was originally described by Orita et al. [94] for the detection of point mutations. The idea of SSCP is to perform electrophoresis on a non-denaturing polyacrylamide gel using small PCR products after denaturation of the DNA. As the PCR product moves through the gel, it will regain a secondary structure that is sequence dependent (similar to RNA secondary structure). The mobility of the single-stranded PCR products depends on their secondary structure. Therefore, PCR products that possess sequence differences (mutations, insertions or deletions) will have different mobilities. 

An alteration in the sequence of purine and pyrimidine bases in a gene due to a change—a removal or an insertion—of one or more bases may result in an altered gene product. Such alteration in the genetic material results in a mutation whose consequences are discussed in detail in Chapter 38. 

SCF is encoded by the mouse Steel (SI) loci (Zsebo et al, 1990). The Sl-Dickie allele of mutant mice (Sf ) encodes a smaller protein due to deletions of the transmembrane and intracellular domains. SI cells exclusively express a secreted form of SCF (Flanagan et al, 1991). Another mutation of the Steel locus, Sl/Sl, results in complete loss of SCF production (Zsebo et al, 1990). Mutations of both the Steel and SI loci result in similar phenotypic disorders of hematopoiesis characterized by reduction in stem cell numbers, anemia, mast cell- and repair deficiencies (Nocka et al., 1989 McCulloch et al., 1965). Phenotypes of Sf mice show that the membrane inserted SCF must have an... 

Theoretically, mutated or nonfunctional genes could be excised and replaced, and new genes with desired functions could be permanently inserted into the genome. Stable integration of an antisense DNA might also be desirable in some circumstances. Because of the technical difficulties associated with the delivery of nucleic acid-based products selectively to specific target cells in vivo, more experimental information is available for ex vivo human gene therapy. 

The production of apurinic and apyrimidinic sites can both be caused by alkylating agents. When, for example, the N7 of guanine is alkylated, this causes the bond from base to sugar to become labile and so the base can be lost completely. Thus, apurinic sites are formed. Insertion of an incorrect base at this site can then cause a mutation. Loss of purines and pyrimidines can also occur spontaneously. 

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