By Robert Nussbaum MD

ISBN-10: 1416030808

ISBN-13: 9781416030805

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Decondensed chromatin Condensation as \ rn~tosisbeg~ns - , Chromosome replication Meiosis I Four haploid gametes A simplified representation of the essential steps in meiosis, consisting of one round of DNA replication Figure 2-14 w followed by two rounds of chromosome segregation, meiosis I and meiosis 11. pairing or synapsis is normally precise, bringing corresponding DNA sequences into alignment along the length of the entire chromosome. Although the molecular basis of synapsis is not completely understood, electron microscopy reveals that the chromosomes are held together by a synaptonemal complex, a ribbon-like protein-containing structure (Fig.

3-7). The 3' sequence consists of about a dozen nucleotides, of which, again, two, the AG located immediately 5' to the intron-exon boundary, are obligatory for normal splicing. The splice sites themselves are unrelated to the reading frame of the RoshanKetab +98(21) 66963783-8 Thompson &Thompson GENETICS IN MEDV'*" particular mRNA. In some instances, as in the case of intron 1 of the P-globin gene, the intron actually splits a specific codon (see Fig. 3-7). The medical significance of RNA splicing is illustrated by the fact that mutations within the conserved sequences at the intron-exon boundaries commonly impair RNA splicing, with a concomitant reduction in the amount of normal, mature P-globin mRNA; mutations in the GT or AG dinucleotides mentioned earlier invariably eliminate normal splicing of the intron containing the mutation.

Other genes have a number of alternative polyadenylation sites, selection among which may influence the stability of the resulting mRNA and thus the steady-state level of each mRNA. O GENE REGULATION A N D CHANGES I N ACTIVITY OF T H E GENOME Most examples of changes in gene expression are accomplished by alterations in the level of transcription, alternative splicing, or post-translational modification. The activation or repression of a given gene in a given tissue or at a given time during development usually involves changes in transcriptional control, carried out by combinations of specific transcription factors and other proteins interacting with the gene regulatory machinery in response to developmental, spatial, or environmental cues or stimuli.

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Thompson & Thompson Genetics in Medicine, Seventh Edition by Robert Nussbaum MD


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