【word】 严重隐性遗传性儿童疾病的新型遗传学测试

【word】 严重隐性遗传性儿童疾病的新型遗传学测试 严重隐性遗传性儿童疾病的新型遗传学测 试 中华妇幼临床医学杂志(电子版)2011年2月第7卷第1期?67? 28MellorAI,ChandlerP,BabanB,eta1.Specificsubsetsofmurlne14999-50004. dendriticcellsacquirepotentTcellregulatoryfunctionsfollowing31MunirS,IreNouenC,I,uongoC,eta1.Nonstructuralproteins1 CTIA4mediatedinductionofindoleamine2,3dioxygenase[J].and2ofrespiratorysyncytialvirussuppressmaturationofhuman Intlmmunol,2004,16(1o):1391—1401.dendriticcells[J].JVirol,2008,82(17):8780—8796. 29HouW,LiS,WuY,eta1.Inhibitionofindoleamine2,3-dioxy一 32RothoeftT,FischerK,ZawatzkiS,ela1.Differentialresponseof genasemediatedtryptophancatabolismacceleratescrescenticglohumannaiveandmemory/effector,rcellstodendriticcellsinfected meru1onephritis_J].ClinExpImmunol,2009,156(2):363, 372.byrespiratorysyncytialvirus[J].ClinExpImmunol,2007,150 30GonzdlezPA.PradoCE,IeivaED.eta1.Respiratorysyncytial(2):263—27 3. virusimpairsTcellactivationbypreventingsynapseassemblywith(收稿Et 期:2010—0918修回日期:2010—12—10) dendriticcells[J].ProcNatlAcadSciUSA,2008,105(39): 翟松会,王峥.树突状细胞在呼吸道合胞病毒免疫逃逸中的作用研究进展[J/CD3.中华妇幼临床医学杂志:电子版,zol1,7(1): 66—69. 严重隐性遗传性儿童疾病的新型遗传学测试 ? 消息? 题为”CarrierTestingforSevereChildhoodRecessiveDiseasesbyNext—GenerationSequencing”论文发在《科学》出版社旗下的 《科学转化医学》(ScienceTranslationalMedicine)杂志上(2001年1月12日出版),由美国国家基因组资源中心(NationalCenterfor GenomeResources)的研究人员领导的一个科研小组开发了一种新型遗传学测试方法,可用于对怀孕前夫妇进行儿童严重隐性遗传 性疾病筛查.将这项新技术与遗传咨询相结合,可降低严重隐性儿童遗传性疾病发病率,并帮助在新生儿中加速对这些疾病的诊 断.新型遗传检测技术通过基因组分析改善当前医疗服务,降低儿童严重隐性遗传性疾病发病率.然而,在普通大众中开展该妊娠 前疾病携带者筛检测试导致的受试者心理负担及与生殖动力学相关问题,尚需彻底解决.就个人而言,儿童遗传性疾病患儿在普 通大众中并不常见,但这些疾病约占所有婴儿死亡率的2O及所有儿 科疾病住院率的lO却不容忽视. 在过去的数1O年中,有超过1000例与这些疾病有关基因已经被找 到.但在美国,只有5种该类疾病被建议在特定人群中进行 孕前筛检,包括脆性X综合征,在白种人中的囊性纤维化及在阿什克 纳齐犹太后裔中的泰一萨克斯疾病等.目前研发的这种孕前隐 性遗传性疾病携带者测试技术,可同时对数百个DNA样品进行448 种儿童隐性遗传性疾病筛检.该测试基于包括靶基因捕捉和 富集,新一代测序技术及复杂精密生物信息学分析.本研究对约100 例不相关个体进行筛检发现,平均而言,每1例被测试者携带 2或3种儿童严重隐性遗传性疾病突变基因.在常用儿童隐性遗传性 疾病数据库中,约1O这些疾病基因突变错误,因此尚需对该 数据库做仔细审查.尽管本研究数据只是初步的,但在一般人群中 2,3种基因突变表观随机分布,是应对个体进行综合性孕前筛 检测试的证据,而不能仅在标靶人群中对少数特定疾病进行筛检.由 于多数人都可能携带2,3种隐性基突变,他们或许会希望 其伴侣也同时接受检测,以确定其是否可能携带相同隐性突变.假如 出现这种情况,则意味他们有更高几率孕育遗传病患儿. BellCJ,DinwiddieDL.MillerNA,eta1.CarrierTestingforSevereChildhood RecessiveDiseasesbyNext—Generation Sequencing[J].SciTranslMed,20113:65ra4. Of7028disorderswithsuspectedMendelianinheritance,l139arerecessivea ndhaveanestablishedmolecularbasis.Although individuallyuncommon,Mendeliandiseasescollectivelyaccountfort20ofinfantmortalityand10ofpediatrichospitalizati0ns. Preconceptionscreening,togetherwithgeneticcounselingofcarriers,hasresultedinremarkabledeclinesintheincidenceofseveral severerecessivediseasesincludingTay—Sachsdiseaseandcysticfibrosis.H owever,extensionofpreconceptionscreeningtomost severediseasegeneshashithertobeenimpractica1.Here,wereportapreconceptioncarrierscreenfor448severerecessivechildhood diseases.Ratherthancostly,completesequencingofthehumangenome,7717regionsfrom437targetgeneswereenrichedbyhybrid captureormicrodropletpolymerasechainreaction,sequencedbynext_generationsequencing(NGS)toadepthofupto2.7 gigabases,andassessedwithstringentbioinformaticfilters.Ataresultant160×averagetargetcoverage,93ofnucleotideshadat least20×coverage,andmutationdetection/genotypinghad, 95sensitivityand,100specificityforsubstitution,insertion/ deletion,splicing,andgrossdeletionmutationsandsingle-nucleotidepolymorphisms.In104unrelatedDNAsamples,theaverage genomiccarrierburdenforseverepediatricrecessivemutationswas2.8andrangedfrom0to7.Thedistributionofmutationsamong sequencedsamplesappearedrandom.Twenty-sevenpercentofmutationscitedintheliteraturewerefoundtobecommon polymorphismsormisannotated,underscoringtheneedforbettermutationdatabasesaspartofacomprehensivecarriertesting strategy.Giventhemagnitudeofcarrierburdenandthelowercostoftestingcomparedtotreatingtheseconditions,carrierscreening byNGSmadeavailabletothegeneralpopulationmaybeaneconomicalwaytoreducetheincidenceofandamelioratesuffering associatedwithsevererecessivechildhooddisorders.