遗传分析课件

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析发育生物学研究所吴晓晖

xiaohui_wu@.cn遗

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析什么是遗传学？遗传分析有什么用？教学安排遗

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析什么是遗传学？遗传分析有什么用？教学安排遗传与变异遗传：世代间相似的现象变异：个体间的差异什么是遗传学？“Theobjectoftheendowmentwasthepromotionofinquiriesintothephysiologyofheredity

andvariation,astudynowspokenofasGenetics.”

-WilliamBateson,1908

“Fromancienttimesheredityhasbeenlookeduponasoneofthecentralproblemsofbiologicalphilosophy.”

-ThomasHunterMorgan孟德尔之前泛生论：获得性、混合式希波克拉底

(HippokratesofKos,460-370B.C.)达尔文

(CharlesRobertDarwin,1809-1882)亚里斯多德

(Aristotle,384-322B.C.)父精为形，母血为质“Libyaalwaysbearssomethingnew”莫佩尔蒂

(Pierre-LouisMoreaudeMaupertuis,1698-1759)白化病、多趾症克尔路德(JosephGottliebKolreuter,

1733-1806)植物(烟草)育种化学模式孟德尔

(1822-1884)植物杂交实验“Experienceofartificialfertilization,suchasiseffectedwithornamentalplantsinordertoobtainnewvariationsincolor,hasledtotheexperimentswhichwillherebediscussed.Thestrikingregularitywithwhichthesamehybridformsalwaysreappearedwheneverfertilizationtookplacebetweenthesamespeciesinducedfurtherexperimentstobeundertaken,theobjectofwhichwastofollowupthedevelopmentsofthehybridsintheirprogeny.”

-GregorJohanMendel,1865“...now,aftereightyears'pursuit,concludedinallessentials.”/分离定律性状

(character)

紫红花:显性

(dominant)

白花:隐性

(recessive)颗粒式遗传自由分离AAaaAaAaAa,AAaaP0xF1705224xF2杂交单元

(hybridunion)

A a A AA Aa a Aa aaAB,母本

ab,父本A,圆籽粒 a,皱籽粒B,黄色胚乳

b,绿色胚乳ABxabABABAbaBab31510810132ABABbAaBAaBb自由组合定律“在最初两种亲本中，决定每种性状差异的杂交单元是相互独立的。”38 plantswiththesign AB35 ” ” “ Ab28 ” ” " aB30 ” ” " ab65 ” ” ” ABb68 ” ” ” aBb60 ” ” " AaB67 " ” ” Aab138 ” ” ” AaBbaBaBbAbAabab孟德尔定律的重新发现

“IthoughtthatIhadfoundsomethingnew.ButthenIconvincedmyselfthattheAbbotGregorMendelinBrünn,had,duringthesixties,notonlyobtainedthesameresultthroughextensiveexperimentswithpeas,whichlastedformanyyears,asdiddeVriesandI,buthadalsogivenexactlythesameexplanation,asfarasthatwaspossiblein1866.” -CarlErichCorrens,1900

“FromtheseandothernumerousexperimentsIconcludethatthelawofsegregationofhybridsasdiscoveredbyMendelforpeashasaverygeneralapplicationintheplantkingdom,andhasabasicsignificanceforthestudyoftheunitsofwhichthespecificcharactersarecomposed.”-HugoMariedeVries,1900“CorrenshasjustpublishedexperimentswhichalsodealwithartificialhybridizationofdifferentvarietiesofPisumsativumandobservationsofthehybridslefttoself-fertilizationthroughseveralgenerations.Theyconfirm,justasmyown,Mendel’steachings.Thesimultaneous“discovery”ofMendelbyCorrens,deVries,andmyselfappearstomeespeciallygratifying.Eveninthesecondyearofexperimentation,ItoostillbelievedthatIhadfoundsomethingnew.” -EricvonTschermak-Seysenegg,1900摩尔根

(1866-1945)植物杂交实验

“Whythen,weareoftenasked,doyoudraginthechromosomes?OuransweristhatsincethechromosomesfurnishexactlythekindofmechanismthattheMendelianlawscallfor;andsincethereisanever-increasingbodyofinformationthatpointsclearlytothechromosomesasthebearersoftheMendelianfactors,itwouldbefollytocloseone’seyestosopatentarelation.Moreover,asbiologists,weareinterestedinhereditynotprimarilyasmathematicalformulationbutratherasaproblemconcerningthecell,theegg,andthesperm.”-T.H.Morgan,1915细胞分裂与染色体1882年，WaltherFlemming发现染色体和有丝分裂1887年，Edouard-Joseph-Louis-MarievanBeneden发现各物种染色体数目固定与减数分裂1888年，TheodorBoveri发现染色体的独立性和世代连续性1892年，AugustWeismann提出种质论，Weismannbarrier1902年，TheodorBoveri与WalterSutton提出染色体携带遗传信息有丝分裂与减数分裂TheMechanismofMendilianHeredity,1915染色体与连锁群Bateson与Punnett发现遗传连锁(1906)花色与花粉粒性状配对遗传“gameticcoupling”果蝇的染色体与连锁群TheMechanismofMendilianHeredity,1915GroupI(47)AbnormalBarBifidBow…GroupII(27)AntleredApterousArcBalloon…GroupIII(22)BandBeadedCreamIIIDeformed…GroupIV(2)BentEyeless染色体与基因行为的关联分离与自由组合常染色体遗传伴性遗传连锁与交换染色体不分离TheMechanismofMendilianHeredity,1915伴性遗传TheMechanismofMendilianHeredity,1915染色体与基因行为的关联分离与自由组合常染色体遗传伴性遗传连锁与交换染色体不分离TheMechanismofMendilianHeredity,1915

“thechromosomesfurnishexactlythekindofmechanismthattheMendelianlawscallfor;andsincethereisanever-increasingbodyofinformationthatpointsclearlytothechromosomesasthebearersoftheMendelianfactors,itwouldbefollytocloseone’seyestosopatentarelation.”分子生物学Avery:

DNA是遗传物质(1944)Watson&Crick:DNA具有双螺旋结构(1953)Nirenberg&Khorana:三联体密码(1961)Crick:中心法则(1958,1970)Roberts&Sharp:断裂基因(1977)Gilbert&Sanger:DNA测序(1977)人类基因组测序(2003)细胞染色体DNA基因………ATCGGGTATACAT………GCACCTGGAATAAACATATAA………||||||||||||||||||||||||||||||||||………TAGCCCATATGTA………CGTGGACCTTATTTGTATATT………/wiki/Central_dogma_of_molecular_biology什么是遗传学？“Theobjectoftheendowmentwasthepromotionofinquiriesintothephysiologyofheredity

andvariation,astudynowspokenofasGenetics.” WilliamBateson,1908遗传信息的组成与传递、变异与重组、实现与调控遗

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析什么是遗传学？遗传分析有什么用？教学安排什么是遗传分析？用遗传学方法解析生命基因的生物学功能？基因的作用机理？是否和疾病相关？是否有重要利用价值？哺乳类~25,000个基因遗传分析基本思路A参与眼发育破坏基因A通过基因突变个体发现验证功能通过突变相互作用解析机理框架B抑制肿瘤破坏基因BC控制体重破坏基因C……DNA复制ArthurKornberg1958 纯化DNA聚合酶

I(PolI)

体外复制DNA：DNA片段,dNTP,Mg++,聚合酶1959 诺贝尔医学奖

“发现DNA生物合成机理”疑问：1)

体外复制慢：10-20碱基/秒

2)

单链s