Uncovered: New Gene Linked to Type 1 Diabetes in Children

A mutation can dramatically increase the chances of developing the chronic form of diabetes

By Nikhil Swaminathan

A research team has identified a new gene that likely affects a child's chances of developing type 1 diabetes.
The chronic disease—which affects about 20.8 million people in the U.S. and is diagnosed in 13,000 children each year—is an autoimmune disorder, in which disease-fighting cells attack pancreatic cells that produce insulin, a hormone that regulates the level of glucose (sugar) in the blood. A deficit of insulin causes blood glucose levels to spike, which can lead to, among other things, kidney failure, retina damage, heart disease and, in some cases, death. The ability to assess a child's risk of developing the disease or to speed its diagnosis is crucial to managing the illness.


"[Type 1 diabetes] is clearly is one of these complex genetic disorders," involving mutations in several genes acting in concert to predispose someone to the condition, says Hakon Hakonarson, director of The Children's Hospital of Philadelphia's Center for Applied Genomics and lead author of the new study, published this week in the online edition of Nature. "The notion is that people believe that about approximately half of it is explained by genetics and half of it is environmental."
Hakonarson's team conducted a genome-wide scan of about 1,000 pediatric diabetes patients, 1,200 healthy children and 1,000 parents of diabetics to track down any links between the illness and 550,000 known mutations found in their genetic code. They turned up many previously implicated genes—at least eight had been fingered prior to this study—as well as three previously undiscovered changes in one gene on chromosome 16 (of each cell's 23 pairs) that appeared to be related to the condition. "There were three markers in this KIAA0350 gene," Hakonarson says, "all sitting in the middle of the gene."

The researchers successfully replicated their findings in a separate, independent sample of 1,600 diabetes patients in whom they also discovered these three so-called flavors or flaws. According to Hakonarson, two of the gene variations—acting alone—appear to increase one's odds of developing diabetes by 50 percent. Ironically, the third mutation discovered appeared to shield against the disease, decreasing the risk by as much as 50 percent.

Hakonarson says that the function of the protein produced by KIAA0350 is unknown, but that there will likely "be a race among multiple labs [(his included)] to find [that] out." He speculates that it is involved with the mechanism that activates cells that trigger the immune system to destroy insulin-producing cells.

"This was what you call a sort of fast-track phase," Hakonarson says about the new study, in which he and his team identified and characterized only the strongest signals in the genome-wide analysis. Next up: researchers are set examine the 2,000 strongest signals to see if they can identify a "gene network" that may be behind type 1 diabetes.

发现：新的基因相连的1型糖尿病儿童


一个突变可以大大提高的机会，发展慢性型糖尿病

由nikhil swaminathan

一个研究小组已经发现一种新的基因可能会影响一个孩子的机会，发展的1型糖尿病。
慢性病ª影响约20.8万人在美国被确诊为13,000儿童每年ª是一种自身免疫性疾病，而疾病战斗攻击细胞的胰岛细胞产生胰岛素，荷尔蒙监管水平的葡萄糖（糖）在血液中。赤字导致胰岛素，血糖，以穗，可导致除其他事项外，肾功能衰竭，视网膜损伤，心脏病，并在某些病例中，死亡。能够衡量一个孩子的风险开发疾病或加快其诊断的关键是管理疾病。


" [ 1型糖尿病]显然是一个复杂的遗传性疾病， "涉及的突变基因数行事音乐会易患别人的情况，内容缺失hakonarson主任儿童医院的76人的中心应用基因组学与主要作者新的研究，发表在本周网络版的性质。 "的概念是，人们相信约有大约有一半是由解释遗传学和一半是环境" 。
hakonarson队进行了全基因组扫描约1000小儿糖尿病患者， 1200名健康儿童和1000名家长，糖尿病追查任何联系，疾病和550,000已知突变发现其遗传密码。他们把许多以前牵连基因ª至少八个已指在此之前的研究ª以及三个先前未被发现的变化，在一个基因对16号染色体（每个单元的23对） ，似乎受到相关条件。 "有三个标志kiaa0350这个基因， " hakonarson说， "所有坐在中间的基因" 。

科学家成功复制的结果，在一个单独的，独立样本1600糖尿病患者中他们还发现，这三个所谓的香料或缺陷。据hakonarson两个基因变异ª单独行事ª堂，以增加其中的赔率，而罹患糖尿病的50 ％ 。讽刺的是，第三次发现的突变似乎抵挡疾病，降低风险高达百分之五十。

hakonarson表示功能的蛋白质产生kiaa0350不明，但有可能会"的竞赛中多次实验室[ （包括自己） ]找到[ ]列" 。他推测，这是参与机制，激活细胞，触发免疫系统破坏的胰岛素分泌细胞。

"这是你们称之为一种快车道阶段， " hakonarson说，对新的研究，在他和他的团队发现和特点只有最强信号，在全基因组分析。下一步：研究者正在研究一套二千最强信号，看看他们能否找出一个"基因网络" ，可背后的1型糖尿病。