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By Dudoit S., Speed T. P.

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Extra resources for A score test for the linkage analysis of qualitative and quantitative traits based on identity [...]

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Human DNA has overall only 40% G + C and the frequency of the dinucleotide CpG is only 20% of that expected. In addition, many cytosine residues are methylated and this can prevent restriction endonuclease digestion. Thus the enzyme NotI, which recognizes the sequence GCGGCCGC, cuts human DNA into fragments of average size 1000– 1500 kb rather than the 65 kb expected. 1 (Smith et al. 1987). Again, the Schizosaccharomyces pombe genome, which is slightly smaller than that of Saccharomyces cerevisiae, is cut into only 14 fragments (Fan et al.

Nothing could be further from the truth. DNA is dynamic and is constantly subjected to rearrangements, insertions and deletions as a result of the activity of transposable elements. For example, LINE insertions have been found to be responsible for certain cases of haemophilia, thalassaemia, Duchenne muscular dystrophy and chronic granulomatous disease. A particularly striking example is a LINE insertion in the APC gene of adenocarcinoma cells from a colon cancer patient, but not in the surrounding normal tissue (Miki et al.

The behaviour of satellite DNA on density gradient centrifugation frequently is anomalous. When the base composition of a satellite is determined by chemical means it often is different to that 24 Chapter 2 predicted from its buoyant density. One reason is that it is methylated which changes its buoyant density. Once isolated, satellite DNA can be radioactively labelled in vitro and used as a probe to determine where on the chromosome it will hybridize. In this technique, known as in situ hybridization, the chromosomal DNA is denatured by treating cells that have been squashed on a cover slip.

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A score test for the linkage analysis of qualitative and quantitative traits based on identity [...] by Dudoit S., Speed T. P.

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