Molecular Biology for Oncologists by John R. Yarnold (auth.), John R. Yarnold, Michael R.

By John R. Yarnold (auth.), John R. Yarnold, Michael R. Stratton, Trevor J. McMillan (eds.)

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The APC gene was then localized to Sq by linkage analysis in a larger number of polyposis families. 9 GENES ARE CLONED AFTER THEIR CHROMOSOMAL LOCATIONS ARE DISCOVERED The region in a chromosome where the gene lies is narrowed down to a few million base pairs using linkage analysis studies. So-called 'recombinants' are very useful in fulfilling this task; these are patients with the disease due to a predisposition gene, but who have had a recombination event between the genetic marker and the disease gene.

There is usually at least one polymorphic site close to any gene locus. The significance of polymorphisms lies in the fact that they enable homologous (maternal and paternal) chromosomal loci to be distinguished by these minor sequence variations using simple molecular techniques. Individuals who are heterozygous for a polymorphism in a genetic marker appear homozygous if one of the alleles is lost. 4). LOH therefore provides a clue as to the sites of tumour suppressor genes. g. 4 Loss of heterozygosity (allele loss).

R. Stratton and T. J. McMillan. Published in 1996 by Chapman & Hall, London. ISBN 0 412 71270 9 Follicular lymphoma Chronic myeloid leukaemia Some ALL ~cute promyelocytic leukaemia Ewing's sarcoma Melanoma Acute leukaemias t(14;18)(q32;q21) t(9;22)(q34;q 11) t(15; 17)(q21;q22) t(ll;22)(q24;q12) t(12;22)(q13;q12) 11q23/various MLL (llq23) ATFI (12q13) EWS (22q12) FLll (llq24) EWS (22q12) PML (15q21) RARA (17q22) abl (9q34) bcr (22qll) bc/-2 (18q21) IG (14q32) myc (8q24) /G(14q32) Genes involved MLL fusion proteins ATFJ-EWS fusion protein FL/1-EWS fusion protein PML-RARA fusion protein bcr-abl fusion protein Deregulated bcl-2 expression bc/-2 mutation Deregulated myc expression myc mutation Molecular outcome This table demonstrates only a fraction of the recurrent chromosomal translocations that have been cloned in ret:ent years.

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