Polymorphism in regulatory gene sequences 英文参考文献.docVIP

/2000/2/1/comment/2001.1 Opinion Polymorphism in regulatory gene sequences N A Mitchison Address: Department of Immunology, Windeyer Institute of Medical Science, University College London Medical School, Cleveland Street, London W1P 6DB, UK. E-mail: n.mitchison@ucl.ac.uk Published: 20 December 2000 GenomeBiology 2000, 2(1):comment2001.1–2001.6 The electronic version of this article is the complete one and can be found online at /2000/2/1/comment/2001 ? GenomeB (Print ISSN 1465-6906; Online ISSN 1465-6914) Abstract The extensive polymorphism revealed in non-coding gene-regulatory sequences, particularly in the immune system, suggests that this type of genetic variation is functionally and evolutionarily far more important than has been suspected, and provides a lead to new therapeutic strategies. Considerable attention recently has focused on polymor- phisms and their potential subtly to alter protein function in ways that might prove biologically or clinically important. But increasing numbers of polymorphisms are also being identified in the regulatory regions of genes, and here I con- sider the significance of these. Reflecting my perspective as an immunologist, this article takes as its starting point the posy of recently discovered polymorphisms associated with autoimmunity, atopy and resistance to infection that are shown in Table 1. I use the word ?posy? to indicate that, in spite of my effort to make the survey comprehensive, it may well be incomplete. To make sense of the distribution of polymorphisms, I focus here on ?introvert? genes, which have been defined as genes encoding proteins that handle self molecules, as opposed to ?extrovert? genes, which encode proteins that handle foreign molecules that enter the body from outside [1,2]. In the former, non-coding variation pre- dominates, as distinct from extrovert genes, in which the reverse applies, at