2012年10月27日 訊 /生物谷BIOON/ --近日,，科研人員證實(shí)斑馬魚是一種潛在的獨(dú)特的可用于檢測人類身上個(gè)體遺傳差異的一類測試工具，并可能有助于新興領(lǐng)域個(gè)性化醫(yī)學(xué)的發(fā)展，相關(guān)研究由賓夕法尼亞州立大學(xué)醫(yī)學(xué)院科學(xué)家領(lǐng)導(dǎo)完成,。DNA差異或突變導(dǎo)致氨基酸的細(xì)微變化,，而斑馬魚可以用作模型,，來研究這些基因突變產(chǎn)生的生物效應(yīng),。
現(xiàn)代技術(shù)和工具的使用使得個(gè)性化藥物的發(fā)展，也有助于發(fā)現(xiàn)生物和個(gè)體的遺傳差異,。病理學(xué)教授Keith Cheng醫(yī)學(xué)博士說：個(gè)性化醫(yī)學(xué)的一個(gè)主要挑戰(zhàn)是缺乏一個(gè)標(biāo)準(zhǔn)來定義許多重要的在人身上發(fā)現(xiàn)的遺傳密碼基因突變,。目前很難區(qū)分DNA變化引起我們氨基酸變化后所產(chǎn)生的影響。斑馬魚是不錯(cuò)的選擇,，因?yàn)槠渥鳛榧棺祫游锱c人非常相似,，其透明度使得這個(gè)模型生物的胚胎成為強(qiáng)大的遺傳研究工具。
博士后Zurab Tsetskhladze主要測試了兩個(gè)影響皮膚顏色的基因,。Tsetskhladze將正常信使RNA（核糖核酸）注入斑馬魚導(dǎo)致其突變,，科學(xué)家們希望研究細(xì)胞信使RNA產(chǎn)生的蛋白質(zhì)。
Cheng實(shí)驗(yàn)室與斑馬魚的研究,，有助于分析人體皮膚顏色的遺傳差異,。科學(xué)家希望確定這些差異在皮膚癌發(fā)展中發(fā)揮的作用,，希望更好地防止人們罹患癌癥,。研究人員在PLoS ONE發(fā)表了他們的研究結(jié)果。（生物谷：Bioon.com）
doi:10.1371/journal.pone.0047398
PMC:
PMID:
Functional Assessment of Human Coding Mutations Affecting Skin Pigmentation Using Zebrafish
Zurab R. Tsetskhladze*, Victor A. Canfield, Khai C. Ang, Steven M. Wentzel, Katherine P. Reid, Arthur S. Berg, Stephen L. Johnson, Koichi Kawakami, Keith C. Cheng*
A major challenge in personalized medicine is the lack of a standard way to define the functional significance of the numerous nonsynonymous, single nucleotide coding variants that are present in each human individual. To begin to address this problem, we have used pigmentation as a model polygenic trait, three common human polymorphisms thought to influence pigmentation, and the zebrafish as a model system. The approach is based on the rescue of embryonic zebrafish mutant phenotypes by “humanized” zebrafish orthologous mRNA. Two hypomorphic polymorphisms, L374F in SLC45A2, and A111T in SLC24A5, have been linked to lighter skin color in Europeans. The phenotypic effect of a second coding polymorphism in SLC45A2, E272K, is unclear. None of these polymorphisms had been tested in the context of a model organism. We have confirmed that zebrafish albino fish are mutant in slc45a2; wild-type slc45a2 mRNA rescued the albino mutant phenotype. Introduction of the L374F polymorphism into albino or the A111T polymorphism into slc24a5 (golden) abolished mRNA rescue of the respective mutant phenotypes, consistent with their known contributions to European skin color. In contrast, the E272K polymorphism had no effect on phenotypic rescue. The experimental conclusion that E272K is unlikely to affect pigmentation is consistent with a lack of correlation between this polymorphism and quantitatively measured skin color in 59 East Asian humans. A survey of mutations causing human oculocutaneous albinism yielded 257 missense mutations, 82% of which are theoretically testable in zebrafish. The developed approach may be extended to other model systems and may potentially contribute to our understanding the functional relationships between DNA sequence variation, human biology, and disease.
