Rare protection against type 1 diabetes 英文参考文献.docVIP

Minireview Rare protection against type 1 diabetes Robert M Plenge Address: Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. Email: rplenge@ Published: 15 May 2009 Genome Biology 2009, 10:219 (doi:10.1186/gb-2009-10-5-219) The electronic version of this article is the complete one and can be found online at /2009/10/5/219 ? 2009 BioMed Central Ltd Abstract A large population study using ultra-high-throughput DNA sequencing to re-sequence a genetic locus associated with type 1 diabetes reveals rare protective alleles. Unlike inherited Mendelian diseases such as cystic fibrosis, the common complex diseases such as diabetes and heart disease have no single predisposing genetic factor. But, over the years, alleles at various genetic loci that either decrease or increase the risk of developing such diseases, in relation to their incidence in the general population, have been uncovered. Geneticists have made the somewhat artificial distinction between ‘common’ and ‘rare’ when describing alleles at polymorphic genetic loci. Classically, ‘common’ variants are those occurring at a frequency of more than 1% in any one continental population (for example, Europeans, Asians or Africans), whereas ‘rare’ variants are present at a frequency of less than 1%. has generated a catalog of more than 3 million variants in three continental populations (Europeans, Asians and Africans) [2,3]. On the basis of the number of individuals genotyped (n = 90 in each continental population), the HapMap Project was calibrated to study DNA variants of greater than 5% frequency. Phase III of HapMap, which is nearly complete, will push the allele-frequency spectrum to 1% (by genotyping more individuals), and extend the project to other continental populations (by genotyping individuals of different ancest