據(jù)physorg網(wǎng)站2006年7月25日報道，雙胞胎同吃同睡,，很多都無法把他們區(qū)分開來,。一模一樣的雙胞胎一同成長，他們分享著幾乎同樣的東西,，包括他們的基因,。但是，有些時候當從遺傳學上來預測,，他們倆人都應當有健康問題的時候往往只一位會面臨健康問題,。
美國密歇根大學醫(yī)學院科學家們正著手對有著驚人相似的雙胞胎為何在面臨一些像風濕性關節(jié)炎之類的疾病時有如此大的差異展開研究。
美國密歇根大學醫(yī)學院研究人員在風濕性關節(jié)炎或者風濕病中發(fā)現(xiàn)了三種過量表達基因,，研究人員先前并不知道這三種基因與這些疾病有關,。他們同時還發(fā)現(xiàn)非基因因素也影響著這三種基因的表現(xiàn)。雙胞胎體內(nèi)這三種基因表現(xiàn)形勢的差異導致雙胞胎中只有一個會得風濕病,。美國密歇根大學醫(yī)學院研究人員的研究論文刊登在《關節(jié)炎和風濕病》期刊的7月版中,。
風濕病是一種慢性炎癥性疾病，它會對關節(jié)造成損害,。風濕病會引發(fā)疼痛,、令人喪失行動能力和導致骨骼畸形。210萬美國人正忍受著風濕病的折磨,。有很多遺傳因素會令人們存在患風濕病的高風險性,。只有約15%的雙胞胎能夠同時避免風濕病,。
科學家對11對單卵雙胞胎的基因表現(xiàn)方式進行了對比，這些雙胞胎共享著同一個卵子,，具有同樣的遺傳,。他們中只有一個患有風濕病。他們發(fā)現(xiàn)這三種基因在患有風濕病的雙胞胎體內(nèi)的量遠遠高于沒有患風濕病的雙胞胎,。這是首次有關在單卵雙胞胎中檢測基因表現(xiàn)方式來研究風濕病的報道,。
該研究的參與者之一,，美國密歇根大學醫(yī)學院內(nèi)科助理教授約瑟夫?胡洛西特茲醫(yī)學博士說,，“我們正在努力解答風濕病中的一種關鍵問題,，即兩個具有同樣基因的患者為什么會得不同的疾病,。一模一樣的雙胞胎為我們提供了解答此項問題的最佳途徑,。”雙胞胎研究的優(yōu)勢在于他們具有嚴格相同的基因信息,。因此,，基因表現(xiàn)的差異性就完全應當歸功于不同的環(huán)境因素,，而不是遺傳,。這些環(huán)境因素引發(fā)一個隨機基因突變或者影響脫氧核糖核酸的打包方式,。
胡洛西特茲說，“這令患有嚴格相同疾病,、具有嚴格相同癥狀和反應的病人在接受治療時存在很大的可變性,。由環(huán)境因素引發(fā)的基因表現(xiàn)方式的差異性會對脫氧核糖核酸進行修改，從而引發(fā)出大量可變性,。”
科學家將蛋白質(zhì)中最顯著的三種過量基因代碼稱之為laeverin,。laeverin是一種酶,，它可以破壞某種蛋白質(zhì)類型,。科學家們猜測laeverin是通過使軟骨和骨骼退化來加重風濕病對關節(jié)組織損傷的,。另一種以前沒有確認的蛋白質(zhì)基因代碼11β-HSD2,，11β-HSD2可以幫助抑制考的索激素,?？嫉乃骷に乜梢詫毫ψ龀龇磻?，同時還具備抵抗炎癥影響的能力。該研究發(fā)現(xiàn)11β-HSD2在風濕病患者體內(nèi)過量能對風濕病患者的共有特征作出解釋,。胡洛西特茲說,，“很久以前我們就知道風濕病患者體內(nèi)缺乏考的索,。”
美國密歇根大學醫(yī)學院科學家研究發(fā)現(xiàn)的第三種基因代碼為Cyr61,，Cyr61在血管新生過程中扮演著角色,，血管新生是指一個區(qū)域新血管重生的過程。
在風濕病初期階段,，關節(jié)組織開始生長和分裂成一個類似于良性腫瘤的瘤。這個不斷生長的塊分泌使組織退化的蛋白質(zhì),，并利用血管新生來恢復新的血管為這個瘤提供營養(yǎng),。血管新生過程中的Cyr61可能也與這個過程有關,。
胡洛西特茲說,，“我們進行的這項研究只是對該方法可能揭示出來的東西進行了初步研究,。在雙胞胎體內(nèi)還存在大量表現(xiàn)存在差異的基因,。我們僅僅開始著手對風濕病是如何以不同的方式影響人類展開研究,。我們所新發(fā)現(xiàn)的基因?qū)α私饧膊〉谋拘?，推動風濕病新治療策略的制定非常重要,。”
此項研究得到了美國國家衛(wèi)生研究院,、關節(jié)炎基金會,、研究和發(fā)展辦公室和退伍軍人事務部的資助,。
此項研究的主要研究人員為美國密歇根大學醫(yī)學院內(nèi)科系研究員克里斯蒂安?S?哈阿斯醫(yī)學博士和美國密歇根大學醫(yī)學院病理學系助理研究員查德?J?克瑞通,。輔助研究人員為美國密歇根大學醫(yī)學院風濕病系研究員徐軍霹醫(yī)學博士和物理學博士,、病理學系副研究員艾拉?馬因里博士,、風濕病學和內(nèi)科教授艾麗薩?E?科赫醫(yī)學博士,、內(nèi)科系研究調(diào)查員宋寧博士,、病理學和泌尿?qū)W助理教授阿魯爾?M?切奈陽醫(yī)學博士和物理學博士和西北大學醫(yī)學院肯尼恩?海因斯醫(yī)學博士,。
英文原文：
How can identical twins be genetically different?
They sleep together, eat together, and most people find it impossible to tell them apart. Identical twins who grow up together share just about everything, including their genes. But sometimes only one twin will have health problems when genetics predicts both of them should.
Scientists at the University of Michigan Medical School are just beginning to understand how two people who are so similar biologically can be so different when it comes to the development of diseases like rheumatoid arthritis.
U-M researchers have discovered three genes that are over-expressed in rheumatoid arthritis, or RA, that were not known to be associated with the disease before. They also found that non-genetic factors influenced the expression of these genes and that the expression patterns varied between identical twins where only one twin had RA. Results of the U-M study were published in the July issue of Arthritis and Rheumatism.
RA is a chronic inflammatory disease that damages joints. RA causes pain, loss of movement, and bone deformities. It affects 2.1 million Americans. There are many genetic factors that put people at a high-risk for developing RA, yet only 15 percent of identical twins will both develop it.
Scientists compared gene expression patterns of 11 pairs of monozygotic twins, who shared the same egg and were genetically identical, but only one of them had RA. They found three new genes that were significantly over-expressed in the twin with RA compared to the one without the disease. This is the first report for RA that examines gene expression patterns in monozygotic twins.
“This is the crux of the issue we are trying to address in RA -- how two patients can have the same genes but different disease outcomes. Identical twins represent the best experimental system to address this question,” says Joseph Holoshitz, M.D., an associate professor of internal medicine at U-M Medical School and co-author of the study.
The advantage of studying twins is that they start out with the exact same genetic information. Therefore, differences in gene expression are attributable to different environmental factors rather than genetics. Such factors could cause a random genetic mutation or affects how DNA is packaged.
“There’s a lot of variability in the severity of the disease, symptoms, and the response a patient will have to treatment. Differences in the expression of genes caused by environmental factors that modify DNA have a lot to do with this variability,” says Holoshitz.
The most significantly over-expressed of the three genes codes for a protein called laeverin. This is an enzyme that destroys certain types of proteins. Scientists hypothesize that laeverin promotes the tissue damage of the joint found in RA by degrading cartilage and bone.
Another previously unidentified gene codes for a protein called 11β-HSD2 that helps deactivate the hormone cortisol. This hormone is involved in the response to stress and also has anti-inflammatory effects. The discovery that 11β-HSD2 is over-expressed in patients may explain a common characteristic of RA patients.
“It has been known for a long time that there is a deficiency of cortisol in RA patients,” says Holoshitz.
The third gene U-M scientists discovered codes for Cyr61, which plays a role in angiogenesis, a process that recruits new blood vessels to an area.
In the early stages of RA, the tissue in the joint begins to grow and divide similarly to a benign tumor. The growing mass, which secretes proteins that degrade tissue, uses angiogenesis to recruit new blood vessels to supply it with nutrients. The angiogenic factor Cyr61 could be involved with this process.
“This paper describes only a glimpse of what this approach might reveal. There are many other categories of genes where expression varies between twins. We are just beginning to understand how RA is able to affect people in different ways. The newly discovered genes provide important insights into the nature of the disease and facilitate the design of novel treatment strategies for RA,” says Holoshitz.
The study was supported by the National Institutes of Health, the Arthritis Foundation, and the Office of Research and Development, Department of Veterans Affairs.
The lead authors were Christian S. Haas, M.D., a research fellow in the department of internal medicine at U-M Medical School; and Chad J. Creighton, a research assistant in the department of pathology at U-M Medical School. Additional contributing authors from the U-M Medical School were Xiujun Pi, M.D., Ph.D., a research fellow in the department of rheumatology; Ira Maine, Ph.D., research associate in the department of pathology; Alisa E. Koch,M.D., professor of rheumatology and internal medicine, Song Ling, Ph.D., a research investigator in the department of internal medicine; Arul M Chinnaiyan, M.D., Ph.D., an associate professor of pathology and urology. G. Kenneth Haines, III, M.D. from Northwestern University Feinberg Medical School also contributed.
