Globin gene

The stable RN A species are represented by repetitive genes. Indeed some species are known to duplicate these genes into extra-chromosomal copies during periods of development. Thus the amphibian, Xempus sp. contains 500 copies of the sequence coding for ribosomal RNA and several thousand copies of the genes for5SRNA.  

The Structure of Genes.— What is known of the gene structure is summarized by using the most extensively studied genes as examples. 

Globin Genes. Globin mRNA species and, with the exception of histone mRNA, all messenger species so far subjected to detailed investigation, are longer than they need to be to code for their protein This is partly because of the 3 poly A 

All the P related globin genes are closely linked on the DNA and separated from each other by non-transcribed spacers as indicated below. 

These intergene regions are apparently never transcribed but are likely to contain sequences which control transcription. 

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Triplex forming bis-PNA Globin gene (dsDNA) Electroporation None Monkey kidney CVl mRNA level (RT-PGR) [76]... 

Wang G., Xu X., Pace B., Dean D.A., Giazer P.M., Chan P., Goodman S.R., Shokolenko I. Peptide nucleic acid (PNA) binding-mediated induction of human y-globin gene expression. Nucleic Acids Res. 1999, 27 2806-2813. 

Some of this differential expression is achieved by having different regions of chromatin available for transcription in cells from various tissues. For example, the DNA containing the P-globin gene cluster is in active chromatin in the reticulocyte but in inactive chromatin in muscle cells. All the factors involved in the determination of active chromatin have not been elucidated. The presence of nucleosomes and of complexes of histones and DNA (see Chapter 36) certainly provides a barrier against the ready association of transcription fac-... 

Sickle cell disease again provides an excellent example of how recombinant DNA technology can be applied to the smdy of human disease. The substitution of T for A in the template strand of DNA in the P-globin gene changes the sequence in the region that corresponds to the sixth codon from... 

P-Thalassemla (MIM 141900) A very wide variety of mutations in the p-globin gene, including deletions, nonsense and frameshift mutations, and others affecting every aspect of its structure (eg, splice sites, promoter mutants)... 

This is known to be true of globin genes however, because of the possibility of RNA editing, divergence at the amino acid sequence level need not necessarily imply diversity at the DNA sequence level. 

Razin SV, Petrov P, Hancock R (1991) Precise localization of the alpha-globin gene cluster within one of the 20- to 300-kilobase DNA fragments released by cleavage of chicken chromosomal DNA at topoisomerase 11 sites in vivo evidence that the fragments are DNA loops or domains. Proc Natl Acad Sci USA 88(19) 8515-8519... 

RFLP analysis of the p-globin gene for genetic testing has been replaced, by PCR In combination with ASO probes on dot blots. The blot shown here corresponds to the family whose pedigree is shown in Figure T7-9. In the mutant allele, glutamate (E) at codon 6 is replaced by valine (V). 

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