生物谷报道:根据Nature Genetics 7月1日在网上提起发表的一份报告,染色体17中的2个变异影响前列腺癌,其中的一个也影响2型糖尿病。
作者说,17号染色体的长臂以前在家族相关性研究中(被认为)与前列腺癌有关,但是以前没有报道易感变异。Dr. Kari Stefansson和同事分析了17号染色体q(长臂)上的6个SNPs(单核苷酸多态性),显示与他们的基因组范围分析的前列腺癌有一定相关。2个SNPs显示与前列腺癌明显相关,rs4430796(什么意思?)的位点A可增加危险性22%,rs1859962的位点G可增加危险性20%。作者报告,SNP rs4430796定位在TCF2基因的第二个内含子,而rs1859962定位在17号染色体长臂24.3的少基因区。
Figure 1 - A schematic view of the genome-wide association results for chromosome 17q.
Shown are results from the genome-wide association analysis performed in the Icelandic study population. The results plotted are for all Illumina Hap300 chip SNPs that are located between position 30 Mb and the telomere ( 78.6 Mb; build 35) on the long arm of chromosome 17 (blue diamonds). The six SNP markers circled in red and listed in Table 2 all fall within the linkage region described in ref. 8.
原文出处:
Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes
Julius Gudmundsson, Patrick Sulem, Valgerdur Steinthorsdottir, Jon T Bergthorsson, Gudmar Thorleifsson, Andrei Manolescu, Thorunn Rafnar, Daniel Gudbjartsson, Bjarni A Agnarsson, Adam Baker, Asgeir Sigurdsson, Kristrun R Benediktsdottir, Margret Jakobsdottir, Thorarinn Blondal, Simon N Stacey, Agnar Helgason, Steinunn Gunnarsdottir, Adalheidur Olafsdottir, Kari T Kristinsson, Birgitta Birgisdottir, Shyamali Ghosh, Steinunn Thorlacius, Dana Magnusdottir, Gerdur Stefansdottir, Kristleifur Kristjansson, Yu Bagger, Robert L Wilensky, Muredach P Reilly, Andrew D Morris, Charlotte H Kimber, Adebowale Adeyemo, Yuanxiu Chen, Jie Zhou, Wing-Yee So, Peter C Y Tong, Maggie C Y Ng, Torben Hansen, Gitte Andersen, Knut Borch-Johnsen, Torben Jorgensen, Alejandro Tres, Fernando Fuertes, Manuel Ruiz-Echarri, Laura Asin, Berta Saez, Erica van Boven, Siem Klaver, Dorine W Swinkels, Katja K Aben, Theresa Graif, John Cashy, Brian K Suarez, Onco van Vierssen Trip, Michael L Frigge, Carole Ober, Marten H Hofker, Cisca Wijmenga, Claus Christiansen, Daniel J Rader, Colin N A Palmer, Charles Rotimi, Juliana C N Chan, Oluf Pedersen, Gunnar Sigurdsson, Rafn Benediktsson, Eirikur Jonsson, Gudmundur V Einarsson, Jose I Mayordomo, William J Catalona, Lambertus A Kiemeney, Rosa B Barkardottir, Jeffrey R Gulcher, Unnur Thorsteinsdottir, Augustine Kong & Kari Stefansson
Published online: 01 July 2007; | doi:10.1038/ng2062
First paragraph | Full Text | PDF (255 KB) | Supplementary information
相关基因:
TCF2
Official Symbol TCF2 and Name: transcription factor 2, hepatic; LF-B3; variant hepatic nuclear factor [Homo sapiens]
Other Aliases: FJHN, HNF1B, HNF1beta, HNF2, LFB3, MODY5, VHNF1
Other Designations: transcription factor 2
Chromosome: 17; Location: 17cen-q21.3
Annotation: Chromosome 17, NC_000017.9 (33120546..33179181, complement)
MIM: 189907
GeneID: 6928
作者简介:
KARI STEFANSSON
Kari Stefansson, M.D., Dr. Med., is president and CEO of deCode Genetics in Reykjavik, Iceland. He was previously Professor of Neurology, Pathology (Neuropathology), and Neuroscience at Harvard Medical School, and Chief of the Division o f Neuropathology at Beth Israel Hospital in Boston. Stefansson received both an M.D. and Dr. Med. from the School of Medicine at the University of Iceland. He trained in neurology and neuropathology at the University of Chicago where he joined the faculty in 1983; when he left the University in 1993 to join the faculty at Harvard, he was Professor of Neurology and Pathology (Neuropathology) and a member of the Committees on Immunology and Neurobiology.
deCode Genetics is a genomics company that searches for disease genes in the Icelandic population. Until recently, the understanding of the genetic basis of human disease was fairly limited and was confined to classic genetic diseases such as hemophilia and cystic fibrosis. Although research into genetic disease established the concept that certain DNA sequence variations could have a huge impact on individual health, this principle could not be extended to more mainstream diseases such as cancer or diabetes. With the advent of the DNA sequencing and mapping technologies (sequencing is the establishment of the order of nucleotides along a piece of DNA; mapping assigns an order to large genomic fragments so that they can be efficiently sequenced), scientists are now able to more closely study genetic variations between individuals.
The hunt for disease genes begins by choosing a target disease such as osteoporosis or schizophrenia, whose genetic contribution in unknown. Family groups are then identified in which these disease genes are statistically more prevalent than in the general populations. Blood samples are collected from these individuals and their DNA is analyzed in order to identify regions of the genome that are linked to the disease.
The Icelandic population offers an unparalleled opportunity to study disease genetics for the following reasons:
Genetically homogeneous population
Genealogy of population since 1800 available to deCode, including health records.
Broad representation of genetically based diseases, for example, certain cancers, Multiple Sclerosis and cardiovascular disease.
See Kari Stefansson's answers to Ask the Scientists questions.