giao trinh di truyen hoc _ hoang trong phan, truong thi bich phuong, tran quoc dung

Tai lieu chia se tai: wWw.SinhHoc.edu.vnMc lcLi ni u

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11Hong Trng Phn

M uI. Khi nim di truyn hc II. Lc s pht trin ca di truyn hc III. i tng v cc lnh vc nghin cu ca di truyn hc IV. Cc phng php nghin cu ca di truyn hc V.Cc nguyn tc nghin cu v phng php hc tp di truyn hc VI. Di truyn hc vi cng ngh sinh hc, tin hc v cc vn x hi 13 13 13 17 18 20 21 24 24 25 25 26 26 26 27 28 28 28 29 30 31 32 33 33 34 39

Chng 1: C s ca Di truyn hc MendelHong Trng Phn

I. Tiu s Mendel - Cha ca di truyn hc II. i tng v phng php th nghim ca Mendel 1. i tng 2. Phng php III. Lai mt tnh v nguyn l phn ly 1. Kt qu th nghim lai mt tnh 2. Gii thch v kim chng nguyn l phn ly 3. Nguyn l phn ly v tnh ph bin ca n IV. Lai hai tnh v nguyn l phn ly c lp 1. Kt qu th nghim lai hai tnh 2. Gii thch v ni dung nguyn l phn ly c lp V. S di truyn Mendel ngi 1. Cc tnh trng ln 2. Cc tnh trng tri VI. L thuyt xc sut trong d on v phn tch di truyn hc 1. Mt s khi nim v tnh cht c bn ca xc sut 2. Mt s nguyn l xc sut c bn VII. Phng php 2 (Chi-square method) trong nh gi ph hp gia cc s liu quan st v k vng

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Tai lieu chia se tai: wWw.SinhHoc.edu.vnChng 2: M rng v p dng ca Di truyn hc MendelHong Trng Phn

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I. Cc kiu quan h gia cc gene allele i vi mt tnh trng 1. Cc kiu tri hon ton, khng hon ton v ng tri 2. Tc ng ca gene gy cht (lethals) 3. Hin tng a allele (multiple allelism) II. Tnh a hiu ca gene (pleiotropy) III. Cc kiu tng tc gia cc gene khng allele 1. Tng tc b tr (complementary) 2. Tng tc t ch (epistasis) 3. Tng tc cng gp- s di truyn a gene v cc tnh trng s lng IV. Cc mi quan h kiu gene - kiu hnh 1. Thng bin v mc phn ng 2. thm nhp (penetrance) v biu hin (expressivity)

43 43 43 45 46 47 48 49 52 54 59 59 60

Chng 3: C s T bo ca s Sinh sn, Di truyn v Bin dHong Trng Phn

I. Sinh sn hu tnh v tnh n nh ca cc b nhim sc th II. Hnh thi hc nhim sc th eukaryote 1. Kch thc nhim sc th 2. Tm ng v cc kiu nhim sc th 3. Cc kiu bng nhim sc th (chromosomal bands) III. Chu k t bo v nguyn phn 1. Chu k t bo (cell cycle) 2. Nguyn phn (mitosis) IV. Gim phn, s pht sinh giao t v th tinh 1. Gim phn (meiosis) 2. S pht sinh giao t (gametogenesis) 3. S th tinh (fertilization) V. Cc bin i ca nhim sc th 1. Cc bin i v cu trc nhim sc th 2. Cc bin i v s lng nhim sc th

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Tai lieu chia se tai: wWw.SinhHoc.edu.vnChng 4: Di truyn hc Nhim sc th

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Hong Trng Phn 103

I. Trng phi Morgan vi thuyt di truyn nhim sc th 1. Tm quan trng ca rui gim Drosophila 2. Thuyt di truyn nhim sc th II. S xc nh gii tnh (sex determination) 1. S xc nh gii tnh do kiu gene (GSD) 2. S xc nh gii tnh do mi trng (ESD) III. S di truyn lin kt vi gii tnh (sex-linked inheritance) 1. c im di truyn ca cc gene trn nhim sc th X v Y 2. S bt hot ca nhim sc th X v mt s vn lin quan 3. Cc tnh trng gii hn bi gii tnh v chu nh hng ca gii tnh IV. Lin kt v ti t hp ca cc gene trn mt nhim sc th 1. Khm ph v s trao i cho rui gim 2. Lin kt gene hon ton (gim phn khng c trao i cho) V. Trao i cho v lp bn di truyn 1. Tn s ti t hp 2. Bn di truyn 3. Trao i cho bn si VI. Lp bn gene t cc php lai phn tch ba im 1. Trao i cho kp vi vic xc nh trt t v khong cch cc gene 2. nhiu v h s trng hp (coefficient of coincidence) VII. Lp bn bng phn tch b bn (tetrad analysis)

103 103 107 108 108 112 113 113 117 120 121 122 124 125 125 127 131 134 134 137 139

Chng 5: Bn cht Ho hc v Ti bn ca Vt cht Di truynHong Trng Phn 147

I. Bng chng vt cht di truyn l cc nucleic acid 1. Cc th nghim bin np vi khun 2. Tnh n nh ca hm lng DNA cc sinh vt bc cao 3. Cc th nghim virus II. Thnh phn ho hc v cu trc ca DNA 1. Cu trc ca mt nucleotide

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Tai lieu chia se tai: wWw.SinhHoc.edu.vn2. Cu trc chui polynucleotide 3. Thnh phn ho hc v cu trc ca chui xon kp DNA 4. S lc v cc c tnh ho l ca cc nucleic acid III. Kch thc b gene v tnh phc tp v mt tin ho 1. S lc v b gene ca cc virus, prokaryote v eukaryote 2. Mi quan h gia kch thc b gene v tnh phc tp v tin ho 3. Hm lng DNA v nghch l gi tr C 4. V kch thc DNA cc bo quan IV. T chc phn t ca cc nhim sc th 1. Cu trc cht nhim sc 2. S lc cc thnh phn DNA trong b gene eukaryote V. Ti bn DNA (DNA replication) 1. Cc nguyn tc v c im chung ca ti bn DNA 2. Cc enzyme tham gia ti bn DNA 3. C ch ti bn DNA VI. Ti bn ca cc b gene RNA (RNA genomes) 1. c im ti bn ca cc b gene RNA virus 2. Ti bn ca b gene RNA 3. Phin m ngc

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151 152 155 157 157 159 159 161 161 161 163 164 164 167 168 174 174 174 175

Chng 6: Gene v Qu trnh Sinh tng hp ProteinHong Trng Phn 179

I. S pht trin ca khi nim gene 1. Cc quan nim ca Mendel v Morgan v gene 2. Gi thuyt mt gene - mt enzyme ca Beadle v Tatum 3. Quan nim ca Benzer v cc n v cu trc v chc nng di truyn 4. Mi quan h gene - cistron cc prokaryote v eukaryote II. Cu trc v chc nng ca protein 1. Cu trc protein 2. Chc nng protein III. M di truyn 1. Bng chng di truyn hc v m b ba 2. Gii m di truyn

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Tai lieu chia se tai: wWw.SinhHoc.edu.vn3. Cc c tnh ca m di truyn 4. Nhng ngoi l so vi m di truyn "ph bin" 5. S linh hot trong vic kt cp anticodon-codon IV. C ch phin m (transcription) v sa i sau phin m 1. Cc RNA v c im chung ca phin m 2. Cc RNA polymerase ca prokaryote v eukaryote 3. Cc promoter cc prokaryote v eukaryote 4. Cc giai on ca qu trnh phin m 5. S sa i sau phin m i vi cc mRNA eukaryote V. Cu trc v chc nng ca cc loi RNA v ribosome 1. RNA thng tin (messenger RNA = mRNA) 2. RNA vn chuyn (transfer RNA = tRNA) 3. RNA ribosome (ribosomal RNA = rRNA) 4. Ribosome VI. C ch dch m (translation) 1. Hot ho amino acid 2. C ch ca qu trnh dch m (tng hp polypeptide)

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191 192 193 194 194 196 196 197 198 200 200 200 201 201 202 202 202

Chng 7: S iu ho Biu hin ca GeneTrng Th Bch Phng 208

I. Cc nguyn l iu ho v mc kim sot phin m II. iu ho biu hin gene prokaryote 1. Cu trc ca operon 2. iu ho dng tnh operon lactose 3. iu ho m tnh operon tryptophan 4. Phin m d (attenuation) III. iu ho biu hin gene eukaryote 1. S bin i DNA 2. Cc promoter 3. Nhng trnh t tng cng phin m (enhancer) 4. Trnh t bt hot gene (gene silencing) 5. Promoter chn lc (alternative promoter) 6. Splicing chn lc

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Tai lieu chia se tai: wWw.SinhHoc.edu.vnChng 8: t bin Gene, Ti t hp v cc Yu t Di truyn Vn ng

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Trng Th Bch Phng 223

I. t bin gene 1. Cc kiu t bin gene 2. Cc tc nhn gy t bin gene 3. C ch phn t ca cc t bin gene II. Sa cha v bo v DNA III. Cc yu t di truyn vn ng (transposable genetic elements) 1. Cc yu t di truyn vn ng prokaryote 2. Cc yu t di truyn vn ng eukaryote

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Chng 9: S Di truyn T bo chtI. S di truyn t bo cht 1. S di truyn ca cc gene lp th 2. S di truyn ca cc gene ty th 3. Hiu qu dng m ln chiu xon v c II. Lp bn ty th v lp th 1. Lp bn gene ca DNA lp th 2. Lp bn gene ca DNA ty th III. Di truyn hc phn t cc bo quan 1. Cc b gene lp th (cpDNA) 2. Cc b gene ty th (mtDNA)

Trng Th Bch Phng 245

245 245 246 249 251 251 253 254 254 255Hong Trng Phn 258

Chng 10: i cng v Cng ngh DNA Ti t hpI. Cc cng c chnh ca k thut to dng DNA ti t hp 1. Cc enzyme gii hn 2. Cc vector thng dng trong k thut di truyn 3. Thit lp phn t DNA ti t hp in vitro II. To dng gene hay DNA ti t hp 1. Nguyn tc chung 2. Quy trnh to dng gene ti t hp 3. Tng hp v to dng cDNA 258 258 260 261 263 263 264 267


Tai lieu chia se tai: wWw.SinhHoc.edu.vnIII. Cc phng php biu hin cc gene c to dng IV. ng dng ca cng ngh DNA ti t hp 1. Cng ngh DNA ti t hp vi vic nghin cu b gene 2. Cng ngh DNA ti t hp vi y-dc hc 3. K thut di truyn vi cc sinh vt bin i gene

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267 269 269 271 274

Chng 11: Di truyn hc NgiTrn Quc Dung 278

I. Cc phng php nghin cu di truyn hc ngi 1. Phng php phn tch ph h (genealogy analysis) 2. Phng php nghin cu tr sinh i 3. Phng php di truyn t bo hc ngi 4. Phng php nghin cu qun th 5. Cc k thut sinh hc phn t II. Cc phng php lp bn di truyn ngi 1. Phn tch lin kt (linkage analysis) 2. Cc phng php lp bn vt l (physical mapping) III. Nhim sc th Y v cht nhim sc gii tnh ca ngi 1. Nhim sc th Y ca ngi 2. Cht nhim sc th gii tnh ca ngi IV. S di truyn cc gene tri-ln trn nhim sc th thng v nhim sc th gii tnh 1. S di truyn cc gene tri-ln trn nhim sc th thng 2. S di truyn cc gene tri-ln trn nhim sc th gii tnh V. Di truyn y hc 1. Cc bnh di truyn do ri lon chuyn ho v cc bnh nhim sc th 2. C s di truyn ung th VI. T vn di truyn y hc

278 278 279 279 279 280 280 280 280 283 283 284 285 285 286 288 288 291 292

Chng 12: Di truyn hc Qun thHong Trng Phn 296

I. Cc khi nim c bn ca di truyn hc qun th 1. Qun th (population) 2. Cc h thng giao phi

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Tai lieu chia se tai: wWw.SinhHoc.edu.vn3. Vn gene (gene pool) 4. Tn s kiu gene v tn s allele II. Nguyn l Hardy-Weinberg v trng thi cn bng ca qun th 1. Nguyn l Hardy-Weinberg 2. Nhng ng dng ca nguyn l Hardy-Weinberg III. M rng nguyn l Hardy-Weinberg 1. a allele (multiple alleles) 2. Tn s allele sai bit gia hai gii tnh 3. Cc gene lin kt trn X IV. Ni phi (inbreeding) 1. T th tinh (self-fertilization) 2. H s ni phi (inbreeding coefficient) 3. Tnh ton h s ni phi V. Cc nhn t tc ng ln thnh phn di truyn qun th 1. t bin 2. Bin ng di truyn ngu nhin 3. Dng gene hay s di nhp c 4. Chn lc t nhin

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297 297 299 299 302 305 305 308 309 310 311 312 313 315 315 316 316 318



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Li ni un nay, di truyn hc ra i ch mi hn mt trm nm song n pht trin vi mt tc ht sc nhanh chng. c bit l, trong vng 50 nm li y k t ngy James Watson v Francis Crick khm ph ra cu trc phn t DNA, 25/4/1953. S hon thnh vic gii m di truyn bi hai nhm nghin cu ca Marshall Nirenberg v Har Gobind Khorana vo thng 6 nm 1966 v s ra i ca K thut Di truyn v Cng ngh DNA ti t hp vo gia thp nin 1970 l hai s kin ni bt nht k t sau khi sinh hc phn t ra i. K , s hon tt ca D n B gene Ngi vo thng 4 nm 2003 c xem l mt trong nhng k cng thm him v i nht ca loi ngi. Ln u tin con ngi c th c c mt cch y ton b trnh t 3.164.700.000 cp base trong b gene ca mnh. Tt c nhng s kin ni bt ny minh chng mt iu rng: S pht trin cng vi nhng thnh tu t c ca di truyn hc trong thi gian qua qu l v cng to ln! gp phn i mi ni dung gio trnh Di truyn hc theo hng cp nht kin thc cng nh phng php dy v hc b mn bc i hc, chng ti tham cu nhiu ti liu khc nhau v n lc bin son gio trnh trn tinh thn y. Chng ti hy vng rng gio trnh ny s p ng c phn no nhu cu ging dy v hc tp ca ging vin v sinh vin, v cng c th s dng nh mt ti liu tham kho b ch cho gio vin Sinh hc cc trng THPT trong bi cnh i mi gio dc hin nay. Ni dung gio trnh gm phn M u cng vi 12 chng bao qut cc kin thc i cng ca mt gio trnh Di truyn hc. Cc chng 14 cp ch yu ni dung thuc Di truyn hc c in, cc chng 5-10 tp trung vo phn Di truyn hc phn t v chng 12 c xem l phn nhp mn ca Di truyn hc qun th, cn chng 11 l s kt hp gia cc kin thc di truyn c in v hin i trn i tng l con ngi. Cui mi chng u c cc phn Cu hi v Bi tp v Ti liu Tham kho bn c tin n tp v tra cu. Gio trnh Di truyn hc c ra i trong khun kh ca D n Gio dc thuc i hc Hu, v vy mt s kin thc nng cao s c cp trong mt gio trnh ring, nh: Di truyn Vi sinh vt v ng dng,v Cng ngh DNA Ti t hp. Bn cnh , mt s thut ng khoa hc c thng nht s dng bng ting Anh gip ngi hc d dng hn trong vic tip cn vi thng tin qua sch bo nc ngoi hoc internet.



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Gio trnh ny do ThS. Hong Trng Phn (ch bin), TS. Trng Th Bch Phng v TS. Trn Quc Dung l nhng ging vin ang cng tc ti Khoa Sinh hc cc trng i hc S phm v i hc Khoa hc thuc i hc Hu bin son, vi s phn cng nh sau: ThS. Hong Trng Phn bin son phn M u v cc chng 1, 2, 3, 4, 5, 6, 10 v 12; TS. Trng Th Bch Phng bin son cc chng 7, 8 v 9; v TS. Trn Quc Dung bin son chng 11. gio trnh ny kp thi ra mt bn c, chng ti xin trn trng cm n D n Gio dc i hc Hu ti tr cho vic bin son v xut bn gio trnh trong khun kh ca D n Gio dc i hc mc B. Chng ti xin by t lng cm n c bit n GS. TS. Phan C Nhn, Trng i hc S phm H Ni, dy cng c bn tho v cho nhiu kin qu bu cng nh khch l chng ti rt nhiu k t khi cng gio trnh bt u c hnh thnh. Do kh nng cn hn ch, chc chn gio trnh cn nhiu thiu st. Chng ti rt mong nhn c s ph bnh v ch bo ca cc ng nghip v bn c gio trnh c hon chnh hn trong ln in sau. Hu, ngy 25 thng 6 nm 2005 Cc tc gi


Tai lieu chia se tai: wWw.SinhHoc.edu.vnM uI. Khi nim di truyn hc

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Theo quan nim ca Bateson (1906), di truyn hc (genetics) l khoa hc nghin cu cc c tnh di truyn v bin d vn c ca mi sinh vt cng vi cc nguyn tc v phng php iu khin cc c tnh . y, tnh di truyn (heredity) c biu hin s ging nhau gia con ci vi cha m; v tnh bin d (variability) biu hin s sai khc gia cha m v con ci cng nh gia cc con ci vi nhau. Cn lu rng, gene l khi nim cn bn ca di truyn hc cho nn ni dung ca khi nim gene khng ngng c pht trin cng vi s pht trin ca di truyn hc.

II. Lc s pht trin ca di truyn hcS ra i v pht trin ca di truyn hc gn lin vi cng trnh nghin cu ca Gregor Mendel nm 1865. Tuy nhin, trc thi Mendel c bit l t th k XVII c mt s s kin quan trng sau y: (1) S ra i ca knh hin vi s khai bi A.van Leuvenhook (1632-1723); v (2) Sinh hc bt u pht trin mnh vo th k XIX vi s ra i thuyt t bo ca M.Schleiden v T.Schwann (1838,1839) v cc thuyt tin ha ca J.B.Lamarck (1809) v c bit l ca R.C.Darwin (1859). Nhn chung, quan nim ph bin thi by gi vn l s di truyn cc tnh trng tp nhim (inheritance of acquired characters) do Lamarck xut v s di truyn ha hp (blending inheritance), ngha l s pha ln "tinh cha huyt m" con ci. 1. S ra i v pht trin ca di truyn Mendel T u H Lan (Pisum sativum), vi tng v phng php nghin cu c o, nm 1865 Gregor Mendel (Hnh 1) pht hin ra cc quy lut di truyn c s u tin v qua suy ra s tn ti tt yu ca cc n v i truyn c th - nhn t di truyn (genetic factor) - quy nh cc tnh trng c truyn t th h ny sang th h khc m sau ny gi l gene. Tuy nhin, gii khoa hc ng thi khng hiu v do khng th nh gi tm vc v i ca pht minh ny. Hnh 1 G. Mendel Mi n nm 1900, ba nh thc vt hc l Carl Correns (Germany), Hugo de Vries (Netherlands) v Erich von Tschermak (Austria) c lp nhau khm ph li cc quy lut di truyn ca Mendel. V di truyn hc chnh thc ra i t y m ngi sng lp l Mendel.



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Trong nhng nm u th k XX, nh ng dng di truyn Mendel, cc nh chn ging pht hin thm cc hin tng nh: tri khng hon ton, ng tri, gene gy cht, a allele, cc kiu tng tc gene... giai on ny, ngoi thuyt t bin ca H.de Vries nm 1901, cn c hai s kin lin quan n s ra i ca thuyt di truyn nhim sc th v di truyn hc qun th sau ny, l s khi xng "thuyt nhim sc th" bi Walter Sutton v Theodor Bovary nm 1902 v vic thit lp quy lut Hardy-Weinberg nm 1908. Mt s thut ng thng dng cng c xut trong giai an ny, nh: di truyn hc (genetics) bi W.Bateson nm 1906, gene, kiu gene (genotype) v kiu hnh (phenotype) bi W.Johannsen nm 1909. 2. S ra i v pht trin ca thuyt di truyn nhim sc th T 1910, Thomas Hunt Morgan (Hnh 2) cng vi ba cng s l Alfred H.Sturtevant, Calvin Bridges v Herman J. Muller xy dng thnh cng thuyt di truyn nhim sc th (chromosome theory of inheritance) da trn i tng nghin cu l rui gim Drosophila melanogaster. Hc thuyt ny xc nhn rng gene l n v c s ca tnh di truyn nm trn nhim sc th ( trong nhn); trn cc gene sp xp theo ng thngHnh 2 T.H.Morgan

to thnh nhm lin kt. Nhng ng gp ng k ca cc mn xut sc ca Morgan l: xy dng bn di truyn (Sturtevant 1913), ch ra c ch xc nh cc kiu hnh gii tnh rui gim (Bridges 1916) v pht trin phng php gy t bin bng tia X (Muller 1927). Vi ng gp to ln Morgan c trao gii Nobel nm 1933 v Muller nm 1946. Nm 1931, Barbara McClintock (Hnh 3) v Harriet Creighton thu c bng chng vt l trc tip v ti t hp ng. Sau , hin tng ny cng c C. Stern quan st Drosophila. Nh vy ti t hp c th c pht hin c v mt vt l ln di truyn ng vt cng nh thc vt. n 1944, McClintock pht hin cc yu t di truyn vn ng (transposable genetic elements), v b c trao gii Nobel nm 1983 v khm ph ny.Hnh 3 B.McClintock

3. S ra i v pht trin ca di truyn hc phn t S ra i ca di truyn hc phn t (molecular genetics) gn lin vi cc khm ph v DNA (deoxyribonucleic acid) t gia th k XX trn i



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tng nghin cu ch yu l cc vi sinh vt. Tuy nhin, trc Friedrich Miescher (1869) khm ph ra mt hn hp trong nhn t bo gi l nuclein m thnh phn chnh ca n sau ny c bit l DNA.

Hnh 4 Beadle, Tatum, Jacob v Monod (t tri sang)

V mi quan h gia gene v protein, t 1902 Archibald Garrod qua nghin cu bnh alcaptonuria ngi gi rng y l mt tnh trng ln Mendel, c th lin quan ti s sai hng mt enzyme. Bng cc th nghim gy t bin cc gene lin quan n cc con ng sinh ha trn nm mc Neurospora, nm 1941 George Beadle v E.L.Tatum (Hnh 4) xc nhn mi gene kim sot s tng hp mt enzyme c th. Chnh gi thuyt mt gene-mt enzyme (one gene-one enzyme hypothesis) ni ting ny m ng cho s ra i ca di truyn ha-sinh, v hai ng c trao gii Nobel cng vi Joshua Lederberg nm 1958. V sau, gi thuyt ny c chnh xc ha l mt gene xc nh ch mt chui polypeptid cu trc s cp ca cc protein, trong c cc enzyme. Vy bn cht ca gene l g? Nm 1944, Oswald Avery (Hnh 5) v cc cng s l MacLeod v McCarty bng th nghim bin np in vitro chng minh rng DNA l vt cht mang thng tin di truyn. Nm 1949, Erwin Chargaff cng b cc kt qu u tin v thnh phn ha hc ca DNA mt s loi.Hnh 5 O.T. Avery

Vic nghin cu cu trc phn t DNA c bt u t 1951 vi cc dn liu nhiu x tia X ca Rosalind Franklin v Maurice Wilkins (Hnh 6). Cc s liu ha hc v vt l ny l c s m t James Watson v Francis Crick (Hnh 7) xy dng thnh cng m hnh cu trc phn t DNA nm 1953, cn gi l chui

Hnh 6 R.Franklin (tri) v M.Wilkins



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xon kp (double helix). Pht minh v i ny m ra k nguyn mi cho s pht trin ca di truyn hc v sinh hc ni chung. Vi pht minh , Watson v Crick cng vi Wilkins c trao gii Nobel nm 1962 . Bi bo nhan "Mt cu trc cho Deoxyribose Nucleic Acid" ca Watson v Crick ng trn tp ch Nature ngy 25/4/1953 c nh giHnh 7 J.D.Watson (tri) v F.H.C.Crick

l mt bi bo khng bnh thng. Ch vn vn c 128 dng nhng ng sau bi bo l c mt bc tin lch s v i ca di truyn hc m mi dng l mt cu chuyn. Tht vy, sau cu trc chui xon kp l hng lot cc khm ph mi. Nm 1958 Matthew Meselson v Franklin Stahl chng minh s ti bn bn bo ton ca DNA; v nm 1961 Seymour Benzer hon tt cng trnh nghin cu cu trc tinh vi ca gene; Francois Jacob v Jacques Monod (Hnh 4) tm ra c ch iu ha sinh tng hp protein (gii Nobel 1965 vi Andre Lwoff); S.Brenner, Jacob v Meselson khm ph ra RNA thng tin; S.Brenner v F.Crick chng minh m ditruyn l m b ba; cng trnh gii mHnh 8 H.G.Khorana (tri) v M.Nirenberg

di truyn ny c hon thnh vo thng 6 nm 1966 bi hai nhm nghin cu ca Marshall Nirenberg v Har Gobind Khorana (gii Nobel nm 1968; Hnh 8). 4. S ra i v pht trin ca cng ngh DNA ti t hp C th ni, nn tng ca cng ngh DNA ti t hp (recombinant DNA technology) c thnh lp t 1972 khi Paul Berg (Hnh 10) to ra phn t DNA ti t hp u tin trong ng nghim (recombinant DNA in vitro). Mt nm sau Herbert Boyer v Stanley Cohen (Hnh 10) ln u tin s dng plasmid to dng DNA. Lnh vc ng dng mi ny ca sinh hc phn t to ra mt cuc cch mng mi trong sinh hc. ng gp ng k trong lnh vc ny l khm ph v cc enzyme gii hn (restriction enzyme) t 1961-1969 ca Werner Arber, Daniel Nathans v



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Hamilton Smith (gii Nobel 1978; Hnh 10); xut cc phng php xc nh trnh t base trong cc nucleic acid nm 1977 bi P.Berg, W.Gilbert

Hnh 9 Cc nh khoa hc ot gii Nobel y hc lin quan k thut gene. T tri sang: D.Nathans, H.Smith, W.Arber, P.Sharp v R.Robert.

Hnh 10 Cc nh khoa hc ot gii Nobel ha hc lin quan k thut gene. T tri sang: H.Boyer, S.Cohen, P.Berg, W.Gilbert, F.Sanger v K.Mullis.

v Frederick Sanger (gii Nobel ha hc 1980; Hnh 10); s khm ph ra cc gene phn on (split gene) nm 1977 bi Phillip Sharp v Richard Robert (gii Nobel 1993; Hnh 9); s pht minh ra phng php PCR (polymerase chain reaction) ca Kary B.Mullis nm 1985 (Hnh 10) v phng php gy t bin nh hng (site-directed mutagenesis) ca Michael Smith t 1978-1982 (gii Nobel ha hc 1993)... Cng vi nhng thnh tu ng dng ly k trong sn xut v i sng x hi, nh vic sn xut cc ch phm y-sinh hc bng cng ngh DNA ti t hp, s dng liu php gene (gene therapy) trong iu tr bnh di truyn, to cc ging sinh vt mi bng con ng bin i gene (genetically modified organisms = GMOs), d n b gene ngi (Human Genome Project = HGP)... gy ra khng t hoi nghi, tranh ci xung quanh cc vn v o l sinh hc (bioethics) v an ton sinh hc (biosafety).

III. i tng v cc lnh vc nghin cu ca di truyn hcTrong giai on u, i tng ca di truyn hc l cc thc vt, ng vt, ngi v cc vi sinh vt. T dn ti s hnh thnh cc lnh vc nghin cu tng ng l di truyn hc thc vt, ng vt, ngi v di truyn hc vi sinh vt, trong di truyn hc t bo l c s. Giai on



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ny ko di t thi Mendel cho n thp nin 1940, vi c trng l nghin cu quy lut di truyn cc tnh trng qua cc th h. V vy n thng c gi l giai on di truyn hc Mendel hay di truyn hc c in (Mendelian or classical genetics). T thp nin 1950 n nay, vi s ra i ca di truyn hc phn t (molecular genetics), i tng nghin cu l t chc, cu trc, chc nng v c ch hot ng ca cc b gene (genomes), cc gene v cc sn phm ca chng mc phn t. c bit vi s ra i ca cc k thut to dng gene (gene-cloning techniques) t thp nin 1970, vic nghin cu c bn cng nh ng dng tr nn ht sc thun li. S phn ha thnh cc chuyn ngnh lc ny l v cng phong ph v a dng, nh: di truyn hc bnh (genetics of disease), di truyn hc ung th (genetics of cancer), di truyn hc pht trin (developmental genetics), cng ngh sinh hc (biotechnology)...Gn y cn xut hin mt s lnh vc nghin cu mi nh genomics, DNA chip technology, DNA microarray technology... Mt hng khc ca di truyn hc chuyn nghin cu cu trc di truyn ca cc qun th v s bin i di truyn bn trong qun th v gia cc qun th. l nhnh di truyn hc qun th (population genetics), m nguyn l c s ca n c G.Hardy (England) v W.Weinberg (Germany) c lp a ra nm 1908. Tuy nhin, lnh vc nghin cu ny ch thc s bt u t thp nin 1930 vi cc cng trnh ca R.A.Fisher, J.B.S.Haldane v Sewall Wright. Ngy nay cc nh di truyn hc khng cn thin v nghin cu s bin i mc kiu hnh m tp trung vo s bin i phn t trong mt qun th nhm tm hiu ngha tin ha ca cc bin i . V nh th di truyn hc qun th tr thnh nn tng cho cc thuyt tin ha hin i. Qua phn tch trn cho thy ba nhnh chnh ca di truyn hc, l: di truyn hc Mendel, di truyn hc phn t v di truyn hc qun th.

IV. Cc phng php nghin cu ca di truyn hcVic nghin cu di truyn hc c tin hnh bi nhiu phng php khc nhau. Bn cnh cc phng php kinh in c th cn c s pht trin v tch hp ca cc phng php t ton hc, tin hc, vt l v ha hc c bit l trong lnh vc sinh hc phn t. 1. Cc phng php kinh in c th ca di truyn hc Trc ht l phng php t th phn dng chn cc dng thun lm b m trong cc php lai, cc phng php lai mt hoc ng thi nhiu tnh trng gia cc b m do Mendel xut. Trong bao gm c cc hnh thc lai thun nghch v lai phn tch (testcross) nhm rt



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ra quy lut, kim tra kiu gene hoc dng thit lp bn di truyn. i vi nghin cu di truyn ngi v mt s vt nui giao phi cn huyt (consanguineous), c trng l phng php phn tch ph h (pedigree analysis) nhm xc nh c im di truyn tri-ln ca mt tnh trng hoc bnh tt; nghin cu tr sinh i cng trng v khc trng nhm xc nh h s di truyn (heritability) ca tnh trng; phng php gy t bin (mutagenesis) kt hp vi lai hu tnh dng trong nghin cu v chn to ging, c bit l thc vt... 2. Phng php ton hc Trong nghin cu khoa hc ni chung v di truyn hc ni ring, vic p dng cc cng c ton thng k v l thuyt xc sut phn tch nh lng v l gii cc kt qu nghin cu l rt thit yu. Chnh iu lm cho di truyn hc tr thnh mt khoa hc chnh xc v mang tnh d bo. iu ny th hin r trong cc cng trnh nghin cu ca Mendel, Morgan cng nh trong cc nghin cu di truyn s lng v di truyn qun th. 3. Cc phng php vt l v ha hc Trong nghin cu di truyn, c bit l di truyn phn t v t bo i hi phi s dng cc k thut v phng php ca vt l v ha hc. Chng hn, trong nghin cu hnh thi nhim sc th khng th thiu cc loi knh hin vi quang hc v in t, cc k thut nhum bng (banding techniques); nghin cu thnh phn ha hc v cu trc DNA i hi cc phng php sc k v nhiu x tia X... 4. Cc phng php t bo hc Trong nghin cu di truyn t bo c rt nhiu phng php c s dng quan st hnh thi nhim sc th v thit lp kiu nhn (karyotype) ca cc loi cng nh chn on cc bnh tt lin quan n s bin i s lng v cu trc nhim sc th. Bn cnh cc k thut nui cy m v chun b nhim sc th l cc k thut nhum bng khc nhau, k thut lai hunh quang ti ch (fluorescence in situ hybridization = FISH), k thut min dch t bo hc... (xem Verma v Babu 1995). 5. Cc phng php ca sinh hc phn t - k thut di truyn S tin b nhanh chng gn y ca sinh hc phn t v cng ngh sinh hc l nh s pht trin mnh m ca cc k thut ti t hp DNA, lai phn t, s dng cc mu d v phng php nh du khc nhau, phng php PCR, cc phng php xc nh trnh t nucleic acid cng nh cc phng php bin i vt liu di truyn mi. Vi cc cng c k thut mi ny cho php i su nghin cu t



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chc ca cc gene v b gene, cc c ch iu ha v bin i di truyn mc phn t cng nh cc thnh tu ng dng mi trong y-sinh hc, nng nghip v cc lnh vc khc ca i sng-x hi. V. Cc nguyn tc nghin cu v phng php hc tp di truyn hc 1. Cc nguyn tc nghin cu ca di truyn hc Trong nghin cu di truyn hc v sinh hc ni chung c cc nguyn tc chung cn tun th nh l phng php lun, sau y: (1) Ly t bo lm n v nghin cu; (2) Thng tin di truyn cha trong b gene t bo chi phi mi biu hin sng ca n m cc gene l n v di truyn c s; (3) S hot ng ca cc gene trong qa trnh pht trin c th l c trng cho tng gene trong tng giai on c th; (4) Cc qu trnh trong cc h thng sng phi c iu ha v kim sot m bo cho s tn ti ca n l lin tc, trong ph bin l s t iu chnh bng cc c ch phn hi thng tin (feed-back mechanism); (5) S thng nht gia cu trc v chc nng biu hin tt c cc mc t chc khc nhau ca s sng; (6) Tt c cc t chc v qu trnh sng u tun theo cc quy lut vt l v ha hc; (7) S sng trn tri t tri qua qu trnh tin ha khong 3,5 t nm qua, v vy khi so snh, nhng nt tng ng gia chng cho thy tnh thng nht v mt ngun gc v nhng nt d bit cho thy tnh pht trin, s phn ha a dng tt yu ca chng. 2. Phng php hc tp mn di truyn hc Cng nh bt k mn hc no khc, vic hc tp mn di truyn i hi phi nm vng lch s mn hc, i tng, nhim v, phng php nghin cu v h thng kin thc cn bn ca n. Bn cnh cc nguyn tc ni trn vn rt cn cho t duy trong hc tp, di y nu mt s im chnh lin quan phng php hc tp c th ca b mn. (1) Nm vng cc kin thc lin mn (nh t bo hc, ha sinh hc, vi sinh hc, hc thuyt tin ha...) v lin ngnh (nh cc khi nim v nguyn l c bn ca ton thng k-xc sut, vt l v ha hu c). (2) Nm vng h thng khi nim c bn cng nh cc thut ng mi khng ngng ny sinh. Trong gene l khi nim cn bn c ni hm khng ngng pht trin, c bit l trong ba thp nin li y. (3) Hiu r bn cht ca cc nguyn l di truyn trong tng ch cng nh mi lin quan gia chng c th gii thch v vn dng trong gii quyt cc bi ton hoc tnh hung ca i sng v thc tin sn xut. (4) nm kin thc v pht trin cc k nng t duy mt cch vng chc i hi phi bit vn dng kin thc vo gii bi tp cng nh cc k nng thc hnh th nghim.



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(5) Di truyn hc l mt khoa hc thc nghim, nn thng tin thu c l nh cc quan st t th gii t nhin, v phng php khoa hc chnh l cng c hiu bit cc quan st . Ni n phng php nghin cu khoa hc l ni n cc bc tin hnh theo mt trnh t t chc cng vic cht ch sau y: Quan st Gi thuyt D on Thc nghim ( kim tra gi thuyt t ra) xut gi thuyt mi. Cng cn lu rng, c tnh ca khoa hc l hoi nghi, i hi phi c bng chng xc thc, l kt hp gia logic v tr tng tng, l gii thch v d on, khng c s c on; ngi nghin cu hay nh khoa hc phi nhn bit sng t, trung thc, v t, v ni chung l chu s chi phi ca cc nguyn tc o c c tha nhn rng ri. (6) Trong khi hc gio trnh, bn nn lm t nht mt tiu lun v mt vn cp nht mnh yu thch. iu rt l th v b ch. Bi cng vic ny i hi s say m tm ti cc thng tin mi, c bit l trn mng vit mt bi tng lun c tnh khoa hc v trnh by trong mt seminar. (7) Bi di truyn hc l mt ngnh khoa hc non tr nhng pht trin vi tc cc nhanh, nn khi lng kin thc mi tch ly c l v cng phong ph v a dng. c th cp nht thng tin v mn hc i hi phi tng cng kh nng s dng ting Anh v internet. iu quan trng l phi to cho mnh mt hoi bo hc tp, mt kh nng v phng php t hc v thnh lp cho c mt th mc tra cu. Trong ng k l cc trang web (c gii thiu trong tng chng), hoc c th s dng ngay cc t kha (key words) c cho tng ch tm kim vi cng c c th ni mnh nht hin nay l Google. VI. Di truyn hc vi cng ngh sinh hc, tin hc v cc vn x hi Nh cp, s pht trin ht sc nhanh chng ca di truyn hc trong vi thp nin qua, c bit l s tin b ca cng ngh sinh hc (biotechnology) ni chung c nhng tc ng mnh m ln nhiu ngnh khoa hc v trn mi mt ca i sng, kinh t, chnh tr v x hi phm vi ton cu. Di truyn hc c hnh dung v tr trung tm v giao thoa vi sinh hc, ha sinh hc, k ngh, y-dc, nng nghip, sinh thi hc, kinh t hc, lut, x hi hc v trit hc. Gio s danh d mn ha hc i hc Havard, F.H.Westheimer, bnh lun v sinh hc phn t nh sau:"Cuc cch mng tr tu v i nht ca 40 nm qua xy ra trong sinh hc. Liu c th tm ra mt ngi no c hc ngy nay m khng hiu bit cht g v sinh hc phn t?" (dn theo Weaver v Hedrick 1997, tr.15). Cc thnh tu t c nh ng dng di truyn hc trong nng nghip



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l v cng to ln, gp phn to nn cuc "cch mng xanh ln th hai" vi s ra i ca hng lot cc ging vt nui-cy trng c u th lai vt tri, cc sinh vt bin i gene (GMOs) mang nhng c tnh hon ton mi l. Trong y hc, l s ra i ca hng lot cc dc phm c sn xut bng k thut di truyn dng cho iu tr bnh v ci bin tr thng minh ca con ngi; l cc phng php chn on v iu tr bnh mc phn t...S thnh cng ca d n b gene ngi (HGP) vo thng 4 nm 2003 cho php chng ta ln u tin c c ton b trnh t khong 3,2 t cp nucleotide trong b gene con ngi (Homo sapiens). HGP l mt trong nhng k cng thm him v i nht trong lch s nhn loi (NHGRI 2005). Theo c tnh mi nht c cng b ngy 21/10/2004 trn tp ch Nature, b gene chng ta cha s lng gene m ha protein thp mt cch ng kinh ngc, khong 20.000 n 25.000 ch khng phi l 50.000 n 140.000 gene nh d on ban u hoc 35.000 theo d on trong vi ba nm li y (NHGRI 2005). Chnh s kt hp tin hc v my tnh trong nghin cu sinh hc phn t dn ti s ra i mt ngnh mi l sinh-tin hc (bioinformatics) cho php thu thp, t chc v phn tch s lng ln cc s liu sinh hc nh s dng mng my tnh v cc ngun d liu (databases). V mt s lnh vc nghin cu mi khc cng ra i nh: genomics - phn tch ton b genome ca mt sinh vt c chn, DNA microchip technology - xc nh cc t bin trong cc gene, DNA microarray technology - nghin cu cch thc mt s lng ln cc gene tng tc ln nhau v c ch mng li iu ha ca t bo kim sot ng thi s lng cc k ln cc gene... Nhng thch thc cho tng lai ca nghin cu khoa hc v cc b gene (genomics) i vi sinh hc, vn sc khe v x hi cng c t ra (Collins v cs 2003). S hon tt ca HGP t n khng c ngha l xong m ng hn l im khi u cho cng cuc nghin cu thm ch cn hng th hn. Cc nh nghin cu hin gi ang c gng lm sng t mt s qu trnh phc tp nht ca sinh hc, l: mt a b pht trin t mt t bo n l bng cch no, cc gene phi hp chc nng ca cc m v c quan nh th no, s tin nh bnh tt xy ra nh th no v b no ngi lm vic ra sao (NHGRI 2005). Cng vi nhng thnh tu ng dng ly k trong sn xut v i sng x hi ni trn, nhiu vn mi c t ra cho cc ngnh gio dc, lut, trit hc, x hi hc v gy khng t hoi nghi, tranh ci xung quanh cc vn v o l sinh hc, an ton sinh hc v mi sinh.


Tai lieu chia se tai: wWw.SinhHoc.edu.vnTi liu Tham kho

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Ting Vit H Hunh Thy Dng. 1997. Sinh hc Phn t. NXB Gio Dc. Phm Thnh H. 2000. Di truyn hc. Ti bn ln II, NXB Gio Dc. Phan C Nhn (ch bin), Nguyn Minh Cng, ng Hu Lanh. 1999. Di truyn hc. NXB Gio Dc. Ting Anh Collins FS, Green ED, Guttmacher AE, Guyer MS. 2003. A vision for the future of genomics research. Nature, Vol. 422, No. 6934, p.835-847. McKusick V. 1998. Mendelian Inheritance in Man. 12th ed., Johns Hopkins University Press, Baltimore. National Human Genome Research Institute (NHGRI)/ National Institute of Health (NIH). 2005: http://www.genome.gov/ http://www.ncbi.nlm.nih.gov/ Online Mendelian Inheritance in Man (OMIMTM): http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM Tamarin RH. 1999. Principles of Genetics. 6th ed, McGraw-Hill, Inc, NY. Verma RS and Babu A. 1995. Human chromosome : principles and techniques. 2nd ed, international edition, McGraw-Hill, Inc., New York. Watson JD and Crick FHC. 1953. A structure for Deoxyribose Nucleic Acid. April 25,1953, Nature, Vol.171, page 737. Weaver RF, Hedrick PW. 1997. Genetics. 3rd ed, McGraw-Hill Companies, Inc. Wm.C.Brown Publishers, Dubuque, IA. Zinnen T. 2005. JD Watson and FHC Crick - A structure for Deoxyribose Nucleic Acid - Nature, 25 April 1953. (http://www.accessexcellence.org)


Tai lieu chia se tai: wWw.SinhHoc.edu.vnChng 1

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C s ca Di truyn hc MendelCho n u th k XX, mi ngi cn cha hiu c c ch ca s di truyn, mc d vn bit rng con ci sinh ra thng ging b m. Quan nim ph bin cho n gia th k XIX c gi gn trong ci gi l thuyt di truyn ha hp (theory of blending inheritance) nhm gii thch s kin con ci mang cc c im ca c hai b m. Tuy nhin, n nm 1866 Gregor Mendel a ra thuyt di truyn gin on (theory of particulate inheritance), vi gi rng: n v di truyn c th kim sot mt tnh trng c truyn t th h ny sang th h khc tn ti di dng ht, ngy nay ta gi l gene. Cc khm ph quan trng ca Mendel t nn mng cho s ra i ca di truyn hc sau ny. Nh Thomas Hunt Morgan nhn nh: "Trong mi nm nghin cu cy u H Lan trong ngi vn ca tu vin, G. Mendel lm nn s khm ph v i nht trong sinh hc t c trong nm trm nm qua".

I. Tiu s Mendel - Cha ca Di truyn hcGregor Mendel sinh nm 1822, ln ln trang tri ca cha mnh ti mt tnh ca Austria (o). V gia nh ngho nn ng phi vo tu vin tip tc vic hc ca mnh. Trong khong thi gian ny, Mendel nghin cu vt l v ton l nhng mn hc gip ng nhiu trong cc th nghim di truyn sau ny. ng c gi ti i hc Vienna thi ly bng gio vin chnh thc, nhng khng v quay v tu vin "dy hc" trong nhiu nm.Hnh 1.1 Gregor Mendel trong ngi vn ca tu vin Brno.

Khi cn trang tri ca cha mnh, Mendel quan tm ti cc cy ci v con vt, v thng gi li nhng ci hoa, con ong v chut. Sau ny tu vin Brno ng tp trung vo cc cy u H Lan (Pisum sativum). Mendel xc nh c cc nguyn l di truyn c s t cc th nghim chn ging thc vt. Cc kt qu nghin cu ny c Mendel trnh by nm 1865 trc Hi Nghin cu Khoa hc T nhin Brno v cng b nm 1866 Germany trong mt bi bo nhan l Cc th nghim lai thc vt (Experiments on Plant Hybrids). Bi bo ny nhanh chng c mt nhiu th vin, nhng nhng ngi cng thi ng khng



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hiu c cc pht hin ca ng, c l mt phn l do ng s dng ton hc l gii cc kt qu ca mnh. Ngoi ra, hu ht cc nh nghin cu ng thi do tin hnh nhiu tnh trng ng thi dn ti cc kt qu ri bi nn khng th nhn ra c cc nguyn l di truyn c s. Mendel tr thnh tu vin trng t nm 1868 v khng cng b thm mt kt qu no v di truyn na k t sau kit tc nm 1866. Mendel qua i nm 1884 trc khi cng trnh ca ng c gii khoa hc thu hiu. Mi n nm 1900, cng trnh ca ng mi c ba nh thc vt hc c lp nhau khm ph li, l Carl Correns ca Germany, Hugo de Vries ca Netherlands v Erich von Tschermak ca Austria. y l mc khi u cho cc nghin cu di truyn hc hin i. Ngy nay, phng php th nghim ca Mendel c xem l th d kinh in v s nghin cu khoa hc c lp k hoch cn thn v bi bo ca ng l s minh ha tuyt vi ca mt thin ti khoa hc.

II. i tng v phng php th nghim ca Mendel1. i tng

(a) (b) Hnh 1.2 (a) By tnh trng tng phn u H Lan c Mendel nghin cu; dng tri nm bn tri ca mi trng hp. (b) Cu to hoa u, phng php th phn cho v cy u H Lan.



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Mendel chn u H Lan (Pisum sativum) lm i tng nghin cu v chng c hai c im c bn l sai khc nhau v nhiu tnh trng tng phn d quan st (hnh 1.2a) v sinh sn bng li t th phn. Ngoi ra, u c hoa kh ln nn thao tc d dng (hnh 1.2b); c kh nng cho s lng i con nhiu; v nhiu ging u lc by gi c gi tr kinh t cao. 2. Phng php Tnh cht c o ca phng php nghin cu Mendel th hin ch: (1) Chn cc dng thun (pure lines) khc nhau bng cch cho t th phn lin tip nhiu th h dng lm dng b m trong cc php lai; (2) Theo di trc tin kt qu di truyn ring bit ca tng tnh trng qua vi th h, trong th h cy lai th nht hay F1 sinh ra do giao phn gia hai dng b m thun chng khc nhau, cn th h cy lai th hai hay F2 sinh ra t s t th phn ca cc cy lai F1, ri sau mi tin hnh nghin cu s di truyn ng thi ca hai hoc nhiu tnh trng; (3) Khi qut v l gii cc kt qu th nghim thu c bng ton thng k v xc sut; v (4) Kim tra li mt cch cn thn cc gi thuyt khoa hc bng cc php lai thun nghch (reciprocal matings) v lai phn tch (testcross).

III. Lai mt tnh v nguyn l phn ly1. Kt qu th nghim lai mt tnh (monohybrid cross) Mendel tin hnh by php lai mt tnh khc nhau v cc kt qu thu c c trnh by Bng 1.1.Bng 1.1 Cc kt qu lai mt tnh ca Mendel F2 TT Kiu hnh P F1 1 Ht trn nhn Trn 5474 trn : 1850 nhn 2 Ht vng xanh Vng 6022 vng : 2001 xanh 3 Hoa ta trng ta 705 ta : 224 trng 4 Qu phng tp Phng 882 phng : 299 tp 5 Qu xanh vng Xanh 428 xanh : 152 vng 6 Hoa dc thn nh Dc thn 651 dc thn : 207 nh 7 Thn cao thp Cao 787 cao : 277 thp T l F2 2,96:1 3,01:1 3,15:1 2,95:1 2,82:1 3,14:1 2,84:1

T tt c cc php lai trn cho thy: Khi b m th h xut pht (P) thun chng khc nhau v mt cp tnh trng tng phn, th th h F1 tt c con lai u biu hin ch mt tnh trng ca b hoc m, tnh trng c gi l tnh trng tri (dominant) v tnh trng kia khng quan st c gi l tnh trng ln (recessive). Sau cho cc con lai F1 t th phn th th h F2 ng thu c c hai kiu hnh (phenotype) ca b m ban u vi t l xp x 3/4 tri v 1/4 ln. Ngoi ra, Mendel cng cho cc cy F2 t th phn ring r v theo di s phn ly th h F3. Kt qu cho thy 1/4 cy ca F2 sinh ra kiu hnh



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ln tt c u l cc cy ln thun chng; iu c ngha l tt c con ci ca chng l ln. Tuy nhin, trong s 3/4 biu hin kiu hnh tri th mt s l tri thun chng, cn s khc th ging nh cc c th F1 ch chng cho i con gm c tri v ln. Nhn chung, c ba kiu c th F2 l: 1/4 tri thun chng, 1/2 tri khng thun chng (cho i con vi t l 3 tri :1 ln) v 1/4 ln thun chng. 2. Gii thch v kim chng nguyn l phn ly T cc kt qu th nghim Mendel kt lun rng, thng qua cc giao t b m truyn cho con ci cc nhn t di truyn (genetic factor) m ngy nay ta gi l gene. Mendel cn gi rng cc nhn t ny tn ti di vi dng bin i (nay gi l cc allele) xc nh cc kiu hnh khc nhau ca cng mt tnh trng. ng gi nh rng mi c th c hai allele ca mi gene, mt ci nhn t giao t ca b v mt ci t giao t ca m. Mc d iu i vi chng ta by gi c v n gin, nhng thi i Mendel khng c ai hiu c n. By gi ta hy xt th nghim 2. Trc tin, quy c cc gene xc nh cc tnh trng tri v ln bng cc ch ci vit hoa v vit thng, chng hn: A - ht vng, v a - ht xanh. Nh vy c ba kiu gene (genotype), trong hai kiu ng hp t (homozygote) - c hai allele ging nhau: AA v aa, tc dng thun chng v mt kiu d hp t (heterozygote) cha hai alele khc nhau: Aa, tc dng lai. V allele vng l tri hn allele xanh, nn c th d hp t Aa c cng kiu hnh vi th ng hp tri AA. P Ht vng (AA) Ht xanh (aa) Giao t P A a F1 Aa (vng) Giao t F1 ( A : a)ci ( A : a)c Khung PunnettA A a AA Aa a Aa aa

F2

T l kiu gene 1 AA : 2 Aa : 1 aa T l kiu hnh 3 vng (A-) : 1 xanh (aa)

Hnh 1.3 S biu din kt qu lai mt tnh ca Mendel.

Trong gim phn, mi b m thun chng ht vng (AA) v ht xanh (aa) ch cho mt loi giao t mang allele tng ng l A v a. Do kt qu ca s th tinh ch to ra mt kiu d hp t Aa, ngha l tt c con lai



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F1 u c kiu hnh tri ht vng. Khi bc vo gim phn, cc c th F1 d hp t (Aa) s cho hai loi giao t (A v a) vi t l tng ng. cng l thc cht ca nguyn l phn ly (principle of segregation), hay quy lut th nht ca Mendel (Mendel's first law). Kt qu ca s t th tinh ngu nhin gia cc loi giao t c v ci ca F1 ny s cho ra bn kiu t hp F2, vi t l phn ly theo kiu gene l 1AA: 2Aa: 1aa v t l kiu hnh tng ng l 3 vng (A-): 1 xanh (aa). Lu rng thng thng ngi ta s dng khung Punnett (Punnett square) do nh di truyn hc ngi Anh R.C.Punnett a ra nm 1905 xc nh kt qu di truyn ca cc php lai. S biu din kt qu lai mt tnh c nu hnh 1.3. khng nh nguyn l phn ly, Mendel tin hnh hai th nghim: Mt l, cho cc c th d hp t F1 t th phn nh ni trn; v hai l, cho F1 lai ngc tr li vi b hoc m c kiu hnh ln. Php lai vi mt c th ln nh th c gi l lai phn tch (testcross), thay v gi l lai ngc (backcross) bi v n cho php kim tra kiu gene ca mt c th tri l d hp hay ng hp. C s di truyn ca kiu lai ny nh sau: B m Aa (ht vng) aa (ht xanh) Giao t 50% A : 50% a 100% a i con 50% Aa (vng) : 50% aa (xanh) 3. Nguyn l phn ly v tnh ph bin ca n Sau khi cc nguyn l di truyn ca Mendel c khm ph li nm 1900, tnh ph bin ca cc nguyn l Mendel ni chung v nguyn l phn ly ni ring c cc nh nghin cu khng nh bng cch lp li cc php lai ca ng (chng hn gia u ht vng v ht xanh; bng 1.2) cng nh tin hnh cc php lai tng t cc ng vt v thc vt khc.Bng 1.2 Cc kt qu lai lp li u H Lan Nh nghin cu Mendel (1866) Correns (1900) Tschermak (1900) Bateson (1905) Darbishire (1909)Tnh ton b

Vng 6.022 1.394 3.580 11.902 109.060131.958

Nhn 2.001 453 1.190 3.903 36.18643.733

T l F2 3,01:1 3,08:1 3,01:1 3,05:1 3,01:13,02:1

Ni dung chnh ca nguyn l hay quy lut phn ly c th tm lc nh sau: Cc allele l nhng dng khc nhau ca cng mt gene; trong cc th d hp t chng phn ly v cc giao t vi t l tng ng.

IV. Lai hai tnh v nguyn l phn ly c lp1. Kt qu th nghim lai hai tnh (dihybrid cross)



29

xc nh s di truyn ng thi ca nhiu cp tnh trng, Mendel tin hnh nhiu th nghim khc nhau. Bng 1.3 gii thiu kt qu lai hai tnh gia cc ging u thun chng ht vng-trn v ht xanh-nhn.Bng 1.3 Cc kt qu lai hai tnh ca Mendel Th h Ptc F1 F2 Kiu hnh ht Vng-trn xanh-nhn Vng-trn Vng-trn Vng-nhn S lng 315 101 108 32556

Xanh-trn Xanh-nhnTng =

T l F2 (quan st) 9,84 3,16 3,38 1,0

T l F2 (k vng) 9 3 3 1

Vi php lai ny, tt c con lai F1 u c kiu hnh tri kp l ht vng v trn. Khi cho F1 t th phn, F2 xut hin 4 kiu hnh l vng-trn, vng-nhn, xanh-trn v xanh-nhn vi t l xp x 9:3:3:1. 2. Gii thch v ni dung nguyn l phn ly c lp Nu xt t l phn ly ca tng tnh trng F2, ta c: 315 + 101 = 416 vng v 108 + 32 = 140 xanh, xp x 3 vng : 1 xanh. Tng t, v hnh dng ht, ta c 315 + 108 = 423 trn v 101 + 32 = 133 nhn, xp x 3 trn : 1 nhn. iu chng t mi tnh trng u tun theo quy lut phn ly 3 tri :1 ln. Bng cch p dng quy tc nhn xc sut ca cc bin c c lp (xem mc VI), ta d dng chng minh c rng s phn ly ca hai t l ny l hon ton c lp nhau nh d on ban u. Tht vy, (3 vng :1 xanh)(3 trn :1nhn) = 9 vng-trn : 3 vng-nhn : 3 xanh-trn : 1 xanh-nhn. Cn lu l t l 9:3:3:1 ny cng c Mendel tm thy trong khi lp li th nghim vi cc tnh trng khc. T ng mi xy dng nn nguyn l phn ly c lp (principle of independent assortment), cn gi l quy lut th hai ca Mendel (Mendel's second law). Ni dung ca nguyn l ny pht biu rng: Cc allele ca cc gene khc nhau th phn ly mt cch c lp vi nhau trong qu trnh hnh thnh giao t (kt qu l to ra t l 9:3:3:1 th h F2 t mt php lai hai tnh). minh ha cho nhng iu trnh by trn y, ta quy c: A - vng, a - xanh, B - trn, b - nhn. Lu : kim tra li gi thuyt phn ly c lp, Mendel tin hnh lai phn tch gia cc cy vng-trn F1 (AaBb) vi cy xanh-nhn (aabb). Kt qu thu c gm 55 vng-trn : 49 vng-nhn : 51 xanh-trn : 53



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xanh-nhn, tng ng vi t l 1:1:1:1 = (1:1)(1:1). iu chng t cc cy F1 cho bn loi giao t vi t l ngang nhau, ngha l cha hai cp gene d hp phn ly c lp. vng, trn xanh, nhn Ptc Kiu hnh Kiu gene AABB aabb Giao t AB ab F1 Kiu gene AaBb Kiu hnh vng, trn Giao t AB : Ab : aB : ab Khung Punnett AB AB Ab aB ab AABB AABb AaBB AaBb Ab AABb AAbb AaBb Aabb aB AaBB AaBB aaBB aaBb ab AaBb Aabb aaBb aabb

F2

T l kiu gene1/16 AABB + 2/16 AaBB + 2/16 AABb + 4/16 AaBb 1/16 AAbb + 2/16 Aabb 1/16 aaBB + 2/16 aaBb 1/16 aabb

T l kiu hnh= 9/16 vng, trn = 3/16 vng, nhn = 3/16 xanh, trn = 1/16 xanh, nhn

Hnh 1.4 C s di truyn hc ca nguyn l phn ly c lp.

V. S di truyn Mendel ngiCng nh u H Lan, rui gim hay mo, ngi c rt nhiu tnh trng di truyn theo cc quy lut Mendel. Chng hn, theo thng k ca Victor A.McKusick nm 1994, c 6.678 tnh trng v cc bnh n gene. Cho n ngy 8/2/2005, cc s liu v s lng gene v kiu hnh c nu bng 1.4 (OMIM 2005). Ni chung, vic xc nh phng thc di truyn ngi l tng i kh khn, v mi gia nh c t con, thng khng qu 10 ngi. khc phc iu ngi ta s dng phng php phn tch ph h (pedigree analysis). Di y nu mt s tnh trng tri v ln ngi m khng phn tch c im ca cc kiu di truyn (xem chng 11).


Tai lieu chia se tai: wWw.SinhHoc.edu.vnBng 1.4 S lng cc mc NST thng 9517 360 1512 1326 2150 14.865 Lin kt X 423 38 137 134 153 885 Lin kt Y 48 0 2 4 2 56 DNA ty th 37 0 27 0 0 64

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Gene c trnh t bit Gene c trnh t v kiu hnh r M t kiu hnh, c s ph.t r Kiu hnh hay locus Mendel, c s phn t cha bit Cc kiu hnh chnh yu khc c c s Mendel cn kh nghi Tng

Tng 10.025 398 1.678 1.464 2.305 15.870

1. Cc tnh trng ln (recessive traits) ngi, hu ht cc ri lon di truyn l ln (xem bng 1.5). i a s nhng ngi mc cc bnh ny thng c b m u bnh thng v kiu hnh, nhng li mang gene bnh trng thi d hp.Bng 1.5 Mt s ri lon n gene thuc nhim sc th thng ngi (phng theo Campbell v Reece 2001; Lewis 2003) Ri lon Cc ri lon ln Bch tng Ha x nang Galactosemia Gaucher Hemochromatosis Phenylketonuria Bnh hng cu lim (ng hp t) Bnh Tay-Sachs Cc ri lon tri Achondroplasia Bnh Alzheimer Bnh Huntington Hypercholesterolemia Khng dung np lactose Hi chng Marfan Cc triu chng (v nguy c mc phi) Thiu sc t da, tc v mt (1/22.000) Tha cht nhy phi, dch tiu ha, gan Tch ly galactose cc m; tr n; tn thng mt v gan. (1/100.000; x l bng king galactose). Gan v lch sng phng, thiu mu, xut huyt ni C th gi li st; nguy c ly nhim cao, tn thng gan, tim v ty , tha sc t da Tch ly phenylalanyl trong mu; thiu sc t da bnh thng; tr n, hn m, cht tui nh (1/10.000) Tn thng lch v nhiu c quan; nguy c ly nhim cao (1/500 ngi M gc chu Phi; ng tri) Tch ly lipid trong cc t bo no gy suy thoi thn kinh; m mu; cht thi th u Ln vi t chi ngn, u v thn bnh thng Thoi ha tm thn; thng xy ra mun mng Thoi ha tm thn v cc c ng mt kim sot Tha cholesterol trong mu; bnh tim; 1/500 l d hp Khng c kh nng phn gii ng lactose, gy ra tnh trng chut rt sau khi n loi ng ny T chi di nh vn, ngc lm, hng thy tinh th, cc ngn tay mnh khnh, ng mch ch suy yu


Tai lieu chia se tai: wWw.SinhHoc.edu.vnBnh thn a nang Tt nhiu ngn

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Cc bng trong cc qu thn, ur trong mu, huyt p cao, au bng di Tha cc ngn tay, ngn chn

Hai bnh ln in hnh l bch tng v ha x nang. Nhng ngi b bch tng (albino) l do thiu ht sc t melanin, nn da d trng bch, tc v trng en ca mt tr nn nht khc thng (hnh 1.5)... Ha x nang (cystic fibrosis) l mt bnh di truyn gy cht ph bin nht M (USA). Bnh ln ny ph bin nht nhng ngi M da trng gc Capca (Caucasians), vi tn s chung l 1/1.800, ngha l trung bnh c 25 ngi c mt ngi mang allele ln ny (Campbell v Reece 2001) hay i vi tr s sinh l 1/2.500 (Weaver v Hedrick 1997). Ngi b bnh ny c c im l tit ra mt lng d tha cht nhy dy phi, ty v cc c quan khc. Cc cht nhy ny c th lm nhiu lon s th, tiu ha v chc nng ca gan v lm cho ngi bnh ri vo nguy c vim phi v cc bnh truyn nhim khc. Nu khng c iu tr, hu ht tr em mc bnh ny s b cht tui ln nm. Theo thng k ca McKusick nm 1994, c 1.730 mc cho cc locus ln. 2. Cc tnh trng tri (dominant traits) Mc d hu ht cc allele c hi l allele ln, nhng mt s cc ri lon ngi l do cc allele tri (xem bng 1.5). Trong s c mt vi allele khng gy cht, chng hn nh tt tha cc ngn tay v chn (hnh 1.5), hoc c mng da gia cc ngn tay v chn. Cc tnh trng nh c tn nhang, di tai thng cng nh cc kh nng un li hnh ng v gp ngc li ln trn u do cc gene tri n khc nhau kim sot. Theo thng k ca McKusick nm 1994, c 4.458 mc cho cc locus tri.

Hnh 1.5 Mt s v d v di truyn Mendel ngi.T tri sang l bch tng, tt nhiu ngn v dng ln ph bin (achondroplasia).



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Th d in hnh v ri lon tri nghim trng l dng ln ph bin do thoi ha sn gi l achondroplasia (hnh 1.5), u v thn mnh pht trin bnh thng nhng tay chn ngn mt cch bt thng; t l mc bnh ny l khong 1 trn 25.000 ngi. Ch nhng ngi d hp t mi b ri lon ny; cn kiu gen ng hp t tri gy cht phi. Trng hp khc l bnh Huntington (Huntington's disease), mt dng ri lon do s suy thoi ca h thn kinh thng xy ra t sau tui trung nin. Khi bnh tin trin, n lm cho cc c ng trn mi phn ca c th mt kh nng kim sot. S mt mt cc t bo no dn ti mt tr nh v kh nng suy xt, gp phn y nhanh s suy thoi. Cui cng, mt lun cc k nng vn ng lm cho khng nut v ni nng c. Ci cht thng xy ra sau khi cc triu chng bt u biu hin khong 10-20 nm (Campbell v Reece 2001).

VI. L thuyt xc sut trong d on v phn tch di truyn hc hiu r cc pht hin ca Mendel v cc nguyn l ca di truyn hc ni chung, cng nh vn dng cc kin thc ny mt cch c hiu qu vo trong hc tp v thc tin i sng-sn xut, chng ta cn nm vng mt vi khi nim v nguyn l xc sut c bn sau y. 1. Mt s khi nim v tnh cht c bn ca xc sut (1) Mt cch n gin, xc sut (probability) c nh ngha bng s ln xy ra mt bin c hay s kin (event) c th chia cho tng s c may m bin c c th xy ra. Nu ta k hiu xc sut ca bin c A l P(A), m l s ln xut hin ca A v n l tng s php th hay ton b s kh nng c th c, khi : P(A) = m / n; trong 0 m n, v n > 0. Nh vy, 0 P(A) 1. (2) Php th l vic thc hin mt nhm cc iu kin xc nh, v d mt th nghim tung ng xu hay gieo ht xc xc hoc mt php lai c th. Cc kt cc khc nhau c th c t php th gi l cc bin c, c k hiu bng cc ch ci in hoa A, B, C...V d: Khi tung mt ng xu, s kin xy ra ch c th l mt sp (S) hoc nga (N) vi xc sut tng ng l 0,5. Tng t, kiu gene d hp Aa c th to ra hai loi giao t mang A v a vi xc sut ngang nhau l 0,5 trong khi cc kiu gene ng hp nh aa chng hn ch cho mt loi giao t mang a; v vy i con ca php lai phn tch Aa aa c t l k vng l 0,5 Aa : 0,5 aa. Khi thc hin php th c th xut hin mt trong cc loi bin c sau: -Bin c ngu nhin (A) l s kin c th xy ra nhng cng c th khng, 0 P(A) 1. -Bin c chc chn ( ) l s kin nht thit xy ra, P() = 1.



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-Bin c khng th c () l s kin nht thit khng xy ra, P() = 0. -Bin c xung khc: Hai bin c A v B gi l i xung khc vi nhau nu tch ca chng l mt bin c khng th c: AB = P(AB) = 0 v P(AB) = P(A) + P(B). -Bin c i lp: "khng A" () c gi l bin c i lp ca bin c A khi = \ A v A= . Khi P() = 1 P(A). -Nhm y cc bin c hay khng gian bin c s cp () l tp hp ton b cc bin c s cp () ca mt php th m khi c thc hin th nht thit mt trong chng phi xy ra, v c hin tng xung khc tng i. V d, dy cc bin c B1, B2,..., Bn lp thnh mt nhm y nu tho mn hai iu kin: (i) Tng ca chng l mt bin c chc chn: B1 B2 ... Bn = ; v (ii) Chng xung khc tng i mt: BiBj = ; ij (i, j = 1,2,...,n). 2. Mt s nguyn l xc sut c bn 2.1. Quy tc cng Quy tc cng pht biu rng: xc sut kt hp ca hai (hoc nhiu) s kin xung khc tng i xy ra l tng cc xc sut ring r ca chng. (i) Vi A, B l hai bin c bt k, ta c P(AB) = P(A) + P(B) P(AB) (ii) Nu A v B l hai bin c xung khc, th: P(AB) = P(A) + P(B) (iii) H qu: Nu l bin c i lp ca A, th P() = 1 P(A). V d, vi kiu gene Rr, nu ta k hiu xc sut ca loi giao t mang allele R l P(R) v ca loi giao t mang allele a l P(r), theo l thuyt ta c: P(R hoc r) = P(R) + P(r) = 1/2 + 1/2 = 1. 2.2. Xc sut iu kin nh ngha: Nu A, B l hai bin c bt k v P(A) > 0, th xc sut iu kin ca bin c B vi iu kin bin c A xy ra l: P(B/A) = P(AB) : P(A). V d: T kt qu th nghim lai gia hai th u thun chng ht vng v ht xanh ca Mendel, hy tm xc sut mt cy u ht vng F2 l th d hp (Vv). Bng lp lun thng thng ta thy trong s bn kiu t hp F2 c 3 kiu t hp cho kiu hnh ht vng (V-) nhng ch c 2 kiu l d hp (Vv). V vy xc sut cn tm l 2/3. Nu gii theo nh ngha xc sut, ta k hiu: A l s kin ht vng F2 v B l s kin ht vng d hp. Theo l thuyt, F2 c 4 s kin ng kh nng vi t l l 1VV: 2Vv: 1vv. y P(A) = 3/4 v P(A.B) = P(B) = 2/4 P(B/A) = P(AB) : P(A) = 2/4 : 3/4 = 2/3.B B



35

2.3. Quy tc nhn T nh ngha v xc sut iu kin, ta i n nh ngha v hai bin c c lp nh sau: Hai bin c A v B c gi l c lp vi nhau nu P(B/A) = P(B) hoc P(A/B) = P(A). Ngha l s xy ra hay khng xy ra ca bin c ny khng nh hng n s xy ra ca bin c kia. Khi , quy tc nhn c pht biu nh sau: Xc sut trng hp ca c hai bin c c lp bng tch cc xc sut ring r ca chng. Ngha l, nu A v B l cc bin c c lp th: P(AB) = P(A).P(B) V d: Khi gieo mt ng xu hai ln lin tip hoc gieo hai ng xu cn i v ng cht cng mt lt th c 4 kh nng xy ra l (SS), (SN), (NS), (NN) vi xc sut ngang nhau. Tht vy, xc sut xut hin c hai mt sp hoc nga l: P(S,S) = P(N,N) = 1/2 1/2 = 1/4; cn xc sut xut hin mt mt sp v mt mt nga l P(S,N) = 2 1/2 1/2 = 1/2; v tng cc xc sut ca tt c cc s kin ng nhin bng 1. T y ta c th xy dng c s ca "php th c lp", nguyn tc gii bi ton lai hai tnh v cc phng php biu din kt qu lai nh sau: (i) Mnh "php th c lp" di y c thit lp da trn quy tc nhn xc sut, ch yu dng kim tra xem quy lut di truyn chi phi ng thi c hai tnh trng no trong mt php lai l c lp hay lin kt (nu l lin kt th lin kt hon ton hay khng hon ton), hoc mt tnh trng no c lin kt vi gii tnh hay khng. Mnh ny c pht biu nh sau: Nu cc gene phn ly c lp v t hp t do, th t l phn ly ng thi ca c hai tnh trng bng tch cc t l phn ly ring r ca cc tnh trng , v ngc li. V d 1: Kt qu ca mt php lai hai tnh c t l phn ly l 3:3:1:1 v cc t l ca tng tnh l 3:1 v 1:1. Ta ni rng cc tnh trng tun theo quy lut phn ly c lp, v: 3:3:1:1 = (3:1)(1:1). V d 2: Kt qu s t th tinh ca mt c th F1(hoc tp giao gia cc c th F1 sinh ra t cc b m thun chng khc nhau v tng cp gene allele) v mt tnh trng no m c t l phn ly l 9:3:3:1 hoc l mt bin dng ca cng thc phn ly . Ta c th khng nh rng tnh trng ny tun theo quy lut tng tc gia cc gene khng allele phn ly c lp. Tht vy, t kt qu trn cho thy i lai c 9+3+3+1 = 16 kiu t hp vi t l ngang nhau, chng t (cc) c th F1 cho t nht 4 loi giao t vi t l tng ng, ngha l d hp t nht 2 cp gene phn ly c lp. Ngha l tnh trng tun theo quy lut tng tc gene. (ii) H qu: Nu tch cc t l phn ly ring r ca cc tnh trng khc vi t l phn ly ng thi ca c hai tnh, chng t cc tnh trng tun



36

theo quy lut di truyn lin kt. V d: Kt qu ca mt php lai cho thy t l phn ly ca c hai tnh l 1A-bb:2A-B-:1aabb hoc 3A-B-:1aabb, trong khi t l phn ly ca mi tnh trng vn l 3:1.Ta d dng thy rng tch (3:1)(3:1) 1:2:1 hoc 3:1, chng t cc tnh trng ny tun theo quy lut lin kt hon ton, v kiu gene ca b m chng i vi trng hp u l Ab/aB Ab/aB hoc AB/ab Ab/aB, v trng hp sau l AB/ab AB/ab. (iii) Nguyn tc tng qut gii mt bi ton lai hai hoc nhiu tnh T nhng iu trnh by trn y cho thy rng thc ra ton lai gm hai dng tng qut: lai mt tnh v lai nhiu tnh, v vic gii mt bi ton lai hai tnh tr ln ni chung c thc hin theo ba bc chnh: Bc 1: Tch xt quy lut di truyn ca tng tnh trng; Bc 2: Gp xt quy lut di truyn ca hai tnh hoc tng hai tnh trng mt ( xc nh xem chng tun theo quy lut no, c lp hay lin kt); v Bc 3: Thit lp (cc) s lai kim chng (xem "Php gii ton lai", Hoa hc tr s 362 tr.40-41). Nh vy, ci kh ca cc bi ton lai thc ra l dng lai mt tnh, v ci kh nht ca dng ton ny l xc nh cho c quy lut chi phi tnh trng v cc kiu quan h c th c gia cc gene allele cng nh gia cc gene khng allele vi nhau. T mi c th xc nh cc kiu gene, kiu hnh, v cui cng l kim chng cc kt qu bng s lai thch hp. (iv) Cc phng php biu din kt qu lai: Bi v bt c mt mnh quy lut no cng l "mnh ko theo" v c tnh xc sut (ngha l cha ng kh nng tin on tim tng), cho nn vic tnh ton v biu din cc kt qu k vng ca bt k mt php lai no r rng l u da trn c s xc sut m ch yu l quy tc nhn. C nhiu cch khc nhau trong biu din kt qu ca cc php lai. Chng hn, trnh by di dng khung Punnett, vn l phng php kinh in ca di truyn hc. Mt phng php thng dng khc l phng php phn nhnh (forked-line approach), Phng php ny c th dng tm xc sut ca cc kiu i con i vi nhiu gene phn ly c lp; n cng rt tin dng khi xc nh thnh phn allele v xc sut ca cc loi giao t t mt kiu gene c th. Ngoi ra, tu trng hp c th s dng trc tip quy tc nhn (product rule). 2.4. Cng thc xc sut nh thc n gin, ta xt php th ng xu gm hai s kin i lp l mt sp (S) v mt nga (N), vi cc xc sut tng ng l p v q, trong q = 1-p. Gi s trong n php th c lp c tin hnh, s kin S xut hin k ln v s kin N l n-k. tnh cc xc sut ny ta phi s dng cng thc xc sut nh thc (binomial probability) sau y:



37

Pn(k) = Ckn .pk.qn-k ; k = 0, 1, 2,..., n. trong , Ckn l h s nh thc; y Ckn = n!/ k!(n-k)! Lu : Dy n php th ny cn gi l dy php th Bernoulli, v n tho mn ba iu kin: (1) N l dy c lp; (2) Trong mi php th, khng gian bin c s cp ch c hai bin c s cp i lp l S v N; v (3) Xc sut ca mt bin c S hoc N l khng thay i trong mi php th, P(S) = p v P(N) = q = 1 p. V d: Gieo mt ng xu lin tip ba ln, c th xy ra 23 = 8 kh nng c lp v th t trong 4 nhm sau y:3 mt sp SSS 2 sp v 1 nga SSN SNS NSS 1 sp v 2 nga SNN NSN NNS 3 mt nga NNN

Vi gi thit p = q =1/2, da vo cng thc xc sut nh thc ta d dng tnh c xc sut ca mi trng hp trn nh sau: P(3 mt sp) = 1(1/2)3(1/2)0 = 1/8 P(3 mt nga) = 1(1/2)0(1/2)3 = 1/8 P(2 sp 1 nga) = 3(1/2)2(1/2)1 = 3/8 P(1 sp 2 nga) = 3(1/2)1(1/2)2 = 3/8 2.5. Cng thc xc sut ton phn Gi s dy B1,B2,...,Bn l mt nhm y cc bin c, ngha l chng c hp l mt s kin tt yu (B1B2...Bn = ) v gm tng i xung khc (BiBj = , vi i j; i,j = 1, 2,...,n); v gi A l mt bin c bt k. Khi : A = A = (B1B2...Bn ) A = (B1 A) (B2 A) ... (Bn A) p dng cc nh l cng v nhn, ta c cng thc xc sut ton phn P(A) = P(B1).P(A/B1) + P(B2).P(A/B2) +...+ P(Bn).P(A/Bn) = P(Bi).P(A/Bi) ; vi i = 1,..,n. 2.6. Cng thc Bayes Vi gi thit nh trn cng thm mt iu kin mi l php th c tin hnh v kt qu l s kin A xy ra. V cc Bi (i= 1, 2,...,n) lp thnh mt nhm y nn cng vi A phi c ch mt s kin Bk no xy ra. Vy khi A xut hin th s kin no trong s cc Bi c nhiu kh nng xy ra hn c? Gii p cu hi ny c ngha l cn tnh xc sutB B B B B



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P(Bk/A). Vn dng nh l nhn xc sut, ta c: P(ABk) = P(A).P(Bk/A) = P(Bk).P(A/Bk) Suy ra: P(Bk/A) = P(Bk).P(A/Bk) : P(A) ; vi P(A) > 0. Thay P(A) t cng thc xc sut ton phn trn, ta c cng thc Bayes nh sau: P(Bk/A) = P(Bk).P(A/Bk) : P(Bi).P(A/ Bi) Trong cc P(Bi) c gi l cc xc sut tin nghim (v chng c xc nh trc khi tin hnh php th), cn P(Bk/A) c gi l xc sut hu nghim (v n ch c xc nh sau khi tin hnh php th). Cn lu rng, cc quy lut Mendel v thc cht l cc nh lut nhn xc sut, cho nn tin on cc nguy c di truyn cn s dng n cng thc Bayes, tc l nh l xc sut ca nguyn nhn. V bi ton t ra ch c th gii quyt trn vn mt khi bit c cc xc sut tin nghim.B B

V d: Ly ngu nhin mt cy u ht vng F2 (trong th nghim ca Mendel) cho lai vi cy ht xanh, v th h lai nhn c tt c l 6 cy ht vng. Hy tm xc sut ca cy ht vng F2 em lai l th ng hp. (Quy c: Y- ht vng, y - ht xanh). Gii: Ta bit rng F2 c t l kiu gene l 1/4 YY : 1/2 Yy : 1/4 yy v t l kiu hnh l 3/4 vng : 1/4 xanh. V cy ht vng (Y-) c chn ngu nhin trong s cc cy ht vng F2 nn n c th l ng hp (YY) hoc d hp (Yy), vi xc sut tng ng l 1/3 hoc 2/3. Gi B1 - s kin "cy ht vng F2 ly ra l th ng hp" B2 - s kin "cy ht vng F2 ly ra l th d hp"; (B1B2 = ) v A l s kin "6 cy ht vng nhn c th h lai". Ta c cc xc sut tin nghim: P(B1) = 1/3 v P(B2) = 2/3 V cc xc sut iu kin: P(A/ B1) = 1 v P(A/ B2) = (1/2)6 = 1/64 Vy xc sut (hu nghim) cn tm l: P(B1/A) = P(B1).P(A/ B1) : [P(B1).P(A/ B1) + P(B2).P(A/ B2)] = (1/31) : [(1/31) + (2/31/64)] = 32/33 = 0,97.B B B

Lu : Kt qu ny cho thy rng cy ht vng F2 (c ly ngu nhin lai phn tch) c kiu gene ng hp l hu nh chc chn (n 97%), vi mc = 0,05. Ni cch khc, ch vi 6 cy ht vng thi cng khng nh s ng tnh ca i con. n y hn l chng ta thy r cng thc Bayes c tm quan trng nh th no trong vic tin on nguyn nhn v nguy c di truyn, cng nh cho php l gii mt s tnh hung phc tp (xem Hong Trng Phn 1995, 2000b).



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VII. Phng php Khi-bnh phng (Chi-square method) trong nh gi ph hp gia cc s liu quan st v k vngNi chung, cc s liu thng k thu c t cc th nghim vn sai khc t nhiu so vi cc con s mang tnh cht l thuyt, tu thuc ch yu vo mu th nghim v phng php ly mu. Trong trng hp , chng ta bn khon khng r liu s gi nh "xp x" ca chng ta c tht chc chn khng? Hay ni theo ngn ng thng k, "gi thuyt tng ng H0 c chp nhn hay b bc b", ngha l kt qu thu c c tht nghim ng vi t l ca mt quy lut no hay khng? c c cu tr li rt ro cho vn ny ch c cch l s dng trc nghim Khi-bnh phng (2-test). y l mt cng c ton thng k thng dng cho php kim tra ph hp gia cc tr s thc t quan st c (observed, k hiu: O) v cc tr s l thuyt c k vng (expected, k hiu: E) ca mt gi thuyt hay phn phi thc nghim khoa hc no , hoc kim tra tnh c lp ca hai i lng ngu nhin. Nh ta c th rt ra quy lut, hoc hiu qu ca hai phng php th nghim no . ng v phng din thc hnh, phng php ny c tin hnh n gin nh sau: Bc 1: t gi thuyt tng ng H0 v sau tnh tr s 2 thc t da theo cng thc: 2 = [(Oi Ei)2/ Ei ] ; i= 1, 2,...,n. Bc 2: Tm tr s 2 l thuyt bng cch tra Bng cc gi tr ca phn phi 2 vi k bc t do. Thng thng ngi ta s dng mc xc sut sai lm P hay mc ngha = 0,05 v k = n 1; trong n l s lp kiu hnh v n cn tu trng hp c th. Mc = 0,05 thng c dng lm ranh gii phn chia gia min n nh chp nhn gi thuyt H0 v min n nh bc b gi thuyt H0. tin li, di y nu ra mt vi tr s 2 = 0,05 l thuyt thng dng ng vi mt s bc t do k nh sau: S bc t do (k) Gi tr 2 = 0,05

1 3,84

2 5,99

3 7,82

4 9,49

Bc 3: So snh cc gi tr 2 thc t v l thuyt. - Nu nh tr s 2 thc t nh hn tr s 2 l thuyt, tc l c mc xc sut P hay > 0,05, gi thuyt H0 c chp nhn. Ngha l kt qu thu c ph hp vi t l c gi nh. - Ngc li, nu nh tr s 2 thc t ln hn hoc bng tr s 2 l thuyt, tc l c mc xc sut P hay 0,05, gi thuyt H0 b bc b. Ngha l kt qu thu c khng ph hp vi t l c gi nh.



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V d: Trong th nghim lai mt tnh ca Mendel, F2 thu c 705 hoa tm v 224 hoa trng. Trn nguyn tc, vi hai kiu hnh F2 khin ta c th ngh ti mt s t l l thuyt gn vi n nh 2:1, 3:1 hoc 9:7. Nhng y t l "tm : trng" thc t l 3,15:1 nn t l k vng hp l hn c l 3:1. chnh l gi thuyt H0 cn kim tra. By gi ta c th tnh ton gi tr 2 thc t nh sau:Kiu hnh Hoa tm Hoa trng Tng S quan st (Oi) 705 224 929 S k vng (Ei) 3/4 929 = 696,75 1/4 929 = 232,25 929 (Oi Ei)2/ Ei 0,098 0,293 2 = 0,391

Bng cch tra bng cc gi tr ca phn phi 2 = 0,05 vi k = 21= 1 bc t do, ta tm c tr s 2 l thuyt l 3,84. V tr s 2 thc t (0,391) nh hn tr s 2 l thuyt (3,84) rt nhiu, nn gi thuyt H0 hon ton c chp nhn. Ngha l kt qu th nghim trn ph hp mt cch st sao vi t l 3:1. iu c ngha rng s sai khc gia cc s liu thc v cc con s l thuyt tng ng l rt khng ng k, khng c ngha v phng din thng k.

Cu hi v Bi tp1. i tng v phng php th nghim ca Mendel c nhng c im c o no m t Mendel khm ph ra cc quy lut di truyn c s u tin, t nn mng cho s ra i ca di truyn hc? 2. Khi lai gia chut en v chut nu nhn c F1 ton chut en. Sau cho cc chut ny tp giao vi nhau thu c F2 gm 53 en v 17 nu. Hy gii thch kt qu, vit cc s lai v tnh xc sut ca mi trng hp phn ly kiu hnh c th c F2 (bit rng s chut F2 thu c t mi t hp lai ca cc chut F1 trung bnh l bn con). 3. T kt qu lai cu sau y, hy xc nh kiu gene ca mi c th. Php lai i con Trng-1 x trng-2 6 trng : 1 en Trng-1 x trng-3 5 trng Trng-1 x en-1 3 trng : 3 en 4. Cho mt rui gim mt nu cnh di giao phi vi mt rui gim mt cnh di. i con thu c gm 51 di, 53 nu di, 17 ngn v 18 nu ngn. Hy xc nh kiu gene ca cc rui gim b m.



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5. Da vo cc php lai v kt qa di y, hy bin lun ch ra cc quy lut di truyn v kiu gene ca cc b m trong mi php lai.i con Php lai Vng, trn vng, trn Vng, nhn vng, nhn Xanh, trn vng, nhn Vng, trn 45 0 31 Vng, nhn 15 42 29 Xanh, trn 16 0 32 Xanh, nhn 5 15 30

6. Gi s thc hin php lai gia con mo lng ngn, tha, c m trng (llddSs) v mo lng di, rm, c m trng (LlDdSs). Hy trnh by cc phng php nhn xc sut n gin v s phn nhnh tnh t l k vng ca mi mt mo con c kiu hnh sau: lng ngn, tha, khng c m trng; lng ngn, rm, c m trng; v lng di, rm, c m trng. 7. rui gim, mt (se+) l tri so vi mt mu nu ti (se; vit tt ca sepia). Cho hai rui gim mt d hp lai vi nhau, v ly mt con mt i con cho lai tr li vi mt b m mt . C may i con php lai ngc xut hin rui gim mt mu nu ti l bao nhiu? 8. khng nh cc nguyn l di truyn ca Mendel, cc nh nghin cu lp li cc th nghim u H Lan. Ring cc th nghim v mu sc ht, F2 Correns thu dc 1.394 vng v 453 xanh, trong khi Tschermak quan st thy c 3.580 vng v 1.190 xanh. Cc tr s ny c ph hp vi nguyn l phn ly khng? Bn hy chng minh iu bng cng c ton thng k thch hp. 9. Gi s ngi chng b bch tng, ngi v v cc con ca h (mt trai v hai gi) u bnh thng. Khi ln ln, chng lp gia nh vi nhng ngi cng khng mc bnh ny v mi gia nh ny u c mt trai v mt gi bnh thng. Gi s xy ra s kt hn ng huyt gia hai a chu c quan h cu c rut, khi xc sut sinh ra mt trai u lng mc bnh ny l bao nhiu? Hy v s ph h ni trn v gii thch. 10. Gi s bn c mt cy u H Lan thn cao cha r kiu gene. Bn em cy ny lai phn tch vi cy thn thp hoc cho n t th phn v thu c tt c by cy u c thn cao. Hi xc sut cy thn cao em lai kim tra c kiu gene ng hp l bao nhiu?

Ti liu Tham khoTing Vit Nguyn Ngc King 1996. Thng k hc trong Nghin cu Khoa hc.



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NXB Gio Dc, H Ni. Phm Vn Kiu 1998. L thuyt Xc sut v Thng k Ton hc. NXB Khoa hc v K thut, H Ni. Hong Trng Phn 1995. nh gi hin tng ng tnh trong lai phn tch nh cng thc Bayes. Thng tin Khoa hc v Gio dc s 11/1995, tr. 133-138, Trng HSP Hu. Hong Trng Phn 2000a. Php gii ton lai. Hoa hc tr s 362, tr.40-41. Hong Trng Phn 2000b. Cng thc Bayes v php tnh gn ng trong phn tch di truyn hc. Thng bo Khoa hc s 4/2000, tr. 65-76, Trng HSP H Ni. Ting Anh Brooker RJ. 1999. Genetics - Analysis and Principles. Benjamin/ Cummings Publishing Company, Inc., Menlo Park, CA. Campbell NA, Reece JB. 2001. Essential Biology. Benjamin/Cummings, an imprint of Addison Wesley Longman, Inc, San Francisco, CA. Hartl DL, Freifelder D, Snyder LA. 1988. Basic Genetics. Jones and Bartlett Publishers, Inc, Boston - Portola Valley. Lewis R. 2003. Human Genetics: Concepts and Applications. 5th ed, McGraw-Hill, Inc, NY. Online Mendelian Inheritance in Man (OMIMTM): Russell PJ. 2000. Fundamentals of Genetics. 2nd ed, Benjamin/ Cummings Publishing Company, Inc, Menlo Park, CA. Suzuki DT, Griffiths AJF, Miller JH, Lewontin RC. 1989. An Introduction to Genetic Analysis. 4th ed, W-H Freeman and Company, New York. Tamarin RH. 1999. Principles of Genetics. 6th ed, McGraw-Hill, Inc, NY. Weaver RF and Hedrick PW. 1997. Genetics. 3rd ed, McGraw-Hill Companies, Inc. Wm.C.Brown Publishers, Dubuque, IA. Mt s trang web http://www.mhhe..com/lewisgenetics5 htttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM http://fpt.netspace.org/MendelWeb/Mendel.htm http://www.nord-rdb.com/~orphan


Tai lieu chia se tai: wWw.SinhHoc.edu.vnChng 2

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M rng v p dng ca Di truyn hc MendelNt c sc ca cc th nghim Mendel l s nht qun hon ton gia cc quan st v gi thuyt ca ng. Tuy nhin, k t sau khi cc cng trnh ca Mendel c khm ph li, ngi ta cn pht hin ra nhiu ngoi l suy rng t m hnh Mendel. Trong chng ny, chng ta s tm hiu cc vn sau: (i) S khc nhau gia cc kiu tri hon ton, tri khng hon ton v ng tri; (ii) Tc ng ca gene gy cht; (iii) Hin tng a allele; (iv) Tnh a hiu ca gene; (v) Cc kiu di truyn do nhiu gene cng tc ng ln mt tnh trng - tng tc gene; (vi) C s di truyn ca cc tnh trng s lng. Cc kiu di truyn lin kt v lin kt vi gii tnh tuy cng c xem nh l s m rng ca cc nguyn l Mendel, nhng s c trnh by trong mt chng ring, chng 4.

I. Cc kiu quan h gia cc gene allele i vi mt tnh trng1. Cc kiu tri hon ton, khng hon ton v ng tri K t sau nm 1900, ngi ta cn pht hin thm mt s trng hp tri khc nhau, b sung cho t l 3 tri :1 ln ca Mendel. 1.1. Tri hon ton (complete dominance) y l trng hp di truyn tri-ln Mendel. Trong hu ht cc trng hp, allele bnh thng (hay kiu di) tri hon ton so vi cc allele t bin. iu ny c th l gii da trn c s di truyn sinh ha ch, allele tri cho sn phm protein hot ng chc nng bnh thng trong khi allele t bin khng to ra c sn phm c hot tnh. Do cc c th ng hp v allele ln khng hon thnh c con ng chuyn ha c lin quan n gene ny. ngi, l trng hp ca cc allele t bin ln gy bch tng, bnh phenylxtn-niu (phenylketonuria = PKU)... Tuy nhin, mt s trng hp, allele t bin tri hn kiu di; ngha l allele kiu di l ln. V d: ngi, kiu ln ph bin do khng to c sn l tri, cho nn cc th d hp biu hin kiu hnh t bin. 1.2. Tri khng hon ton (incomplete dominance) Khi lai gia hai ging hoa bn gi (four-o'clock; Mirabilis jalapa) thun chng c hoa mu v hoa mu trng, Carl Correns thu c tt c cc cy F1 c hoa mu hng, kiu hnh trung gian gia hai b m. Sau khi cho cc cy F1 t th phn, t l kiu hnh F2 l 1 : 2 hng : 1 trng. Mc d t l kiu hnh ny c hi lch so vi ca Mendel, nhng



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thc t n tng ng vi t l kiu gene 1:2:1 (hnh 2.1). Nu s dng quy c gene A- l tri khng han ton so vi a- trng, ta c s lai sau: Ptc Hoa (AA) Hoa trng (aa) Aa (Hoa hng) F1 F2 T l kiu gene AA : Aa : aa T l kiu hnh : hng : trng

tri ng hp t

d hp t

ln ng hp t

Hnh 2.1 S di truyn trung gian i vi mu sc hoa nhiu thc vt.

Bi kiu hnh ca th d hp l trung gian gia hai th ng hp, v vy ta c th l gii trn phng din sinh ha rng hm lng sn phm tch ly do mt allele tri kim sot l khng th hin kiu hnh mu nh trong trng hp c mt c hai allelele tri. 1.3. ng tri (codominance) ng tri l hin tng c hai allele khc nhau trong mt th d hp cng biu hin ra cc sn phm c hot tnh khc nhau trong t bo. Cc allele nh th c gi l cc allele ng tri. in hnh l trng hp nhm mu AB ca h nhm mu ABO (hnh 2.2; xem gii thch mc 3 bn di) v nhm mu MN ca h nhm mu M-N ngi.

Hnh 2.2 Kiu hnh cc nhm mu A, AB v B. ( y cho thy s ng tri nhm mu AB. Nhm mu O khng c khng nguyn no).

H nhm mu M-N (do mt locus thuc nhim sc th thng kim sot) c hai allele LM v LN. Nh th, trong mt qun th s c ba kiu gene LMLM, LMLN v LNLN (c th vit gn l MM, MN v NN) tng ng vi ba kiu hnh hay nhm mu l M, MN v N. Nu cho rng cc php hn phi thun nghch l tng ng, th c th c su kiu hn phi vi cc t l kiu gene k vng i con c cho bng 2.1.


Tai lieu chia se tai: wWw.SinhHoc.edu.vnBng 2.1 Cc t l k vng i con i vi h nhm mu M-N B m i con

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L L

M M

LMLN

LNLN

LMLM LMLM 1 M M M N L L L L M M N N L L L L 1 M N M N L L L L M N N N L L L L N N N N L L L L 1 Mt v d khc l allele ln gy bnh hng cu hnh lim. nhng ngi d hp t v allele ny (HbAHbS), c hai allele u c biu hin v cc t bo mu ca h cha c hemoglobin bnh thng v bt thng. 2. Tc ng ca gene gy cht (lethal) Cc allele gy cht l nhng t bin c th tri hoc ln lm gim sc sng hoc gy cht i vi cc c th mang n v do , lm bin i t l 3:1 ca Mendel. Nhiu gene c cc allele nh hng ln t l cht ch khng gy cht; cc allele ny c gi l cc allele c hi (deleterious).

Hnh 2.3 Bin i mu lng chut.

Hnh 2.4 Mo Manx khng ui.

Ni chung, cc allele gy cht thng l ln v gy cht cc th ng hp. V d, t bin bch tng thc vt lm cho cy cht giai on non v khng c dip lc quang hp. Bnh thiu mu hng cu hnh lim ngi (xem mc II) c th gy cht vi t l ng k tui trng thnh khi allele t bin ln ny trng thi ng hp. Tuy nhin, mt s allele gy cht l nhng t bin tri. in hnh l th nghim lai v mu sc lng chut ca Lucien Cunot nm 1904. Khi lai gia hai chut thn vng (allele vng l tri; Hnh 2.3), ng thu c t l xp x 2 vng : 1 kiu di. Mt khc, khi lai gia cc chut vng vi chut kiu di (mu agouti), ng thy rng i con c t l xp x 1:1.



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Cunot kt lun rng tt c cc chut vng u l nhng th d hp, cn cc th ng hp v allele vng u b cht giai on phi. B m Yy (vng) Yy (vng) YY : Yy : yy i con(cht) 2 vng : 1 agouti

Hin tng "khng ui" mo Manx (c pht hin u tin o Manx nm 1935; Hnh 2.4) l mt tnh trng khc gy ra bi mt allele t bin tri M; n c hiu qu tri cc th d hp v gy cht cc th ng hp. V vy khi lai gia cc mo Manx (Mm Mm) bao gi cng thu c mo Manx khng ui v c ui bnh thng. 3. Hin tng a allele (multiple allelelism) Trn thc t, mi mt gene khng ch c hai allele m c th c nhiu hn hai allele, gi l a allele. Cc allele l nhng trng thi cu trc khc nhau ca cng mt gene pht sinh do t bin (xem chng 8). Ni chung, nu mt gene trn nhim sc th thng (autosome) c n allele khc nhau, th trong qun th c th c n(n+1)/2 kiu gene, trong c n kiu ng hp v n(n 1)/2 kiu d hp (xem bng 2.2). y chnh l c s ca hin tng a hnh (polymorphism) quan st c trong cc qun th t nhin.Bng 2.2 Mi quan h s lng gia cc allele v cc kiu gene S allele 1 2 3 4 ... n S th ng hp 1 2 3 4 ... n S th d hp 0 1 3 6 ... Tng s kiu gene 1 3 6 10 ...

n(n 1)/2

n(n+1)/2

V d: S di truyn h nhm mu ABO ngi c kim sot bi mt gen autosome c ba allele chnh l IA, IB v IO; trong IO l ln, cn cc allele IA v IB l ng tri. Trong mt qun th, ni chung c su kiu gen tng ng vi bn kiu hnh hay nhm mu sau y: Kiu hnh A B AB O A A A O B B B O A B O O Kiu gene I I ,I I I I , I I I I I By gi ta hy tm hiu c s di truyn min dch ca h nhm mu ABO ny. S khc nhau gia cc nhm mu l do s c mt ca cc loi khng nguyn v khng th . Cc khng nguyn (antigen) y l nhng phn t kt hp protein-ng bm trn b mt ca cc t bo hng cu v



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chng xc nh tn nhm mu tng ng. Cc c th mang allele IA v/hoc allele IB c khng nguyn tng ng A v/hoc B; cn allele IO khng to c bt k khng nguyn no (nn nhng ngi ng hp v allele ln ny c kiu hnh O, ngha l "khng" c khng nguyn A hoc B no c trn b mt cc t bo hng cu). Cc khng th (antibody) l nhng protein do h thng min dch to ra vi mt s lng ln nhm p ng vi cc khng nguyn c th t bn ngoi. C th, trong huyt thanh nhng ngi mang nhm mu O thy c c hai loi khng th khng-A v khng-B gi l v ; nhng ngi nhm mu AB khng c bt k loi khng th no; cn nhng ngi nhm mu A v B ch c mt loi khng th tng ng l v . ngha lm sng ca nguyn tc truyn mu l ch khi truyn sai nhm mu s xy ra phn ng ngng kt cht ngi do phn ng gia khng nguyn b mt ca hng cu ngi cho (donor), m lng huyt thanh l khng ng k, vi khng th c trong huyt thanh ca ngi nhn (recipient). V th, nhng ngi c cng nhm mu th c th cho v nhn ca nhau. c bit, nhm mu O do thiu c hai loi khng nguyn A v B nn c th truyn cho mt ngi mang bt k nhm mu no; ngc li ngi mang nhm mu AB c th nhn bt k nhm mu no. Hin tng a allele tn ti ph bin trong cc qun th sinh vt khc nhau. V d, gene kim sot mu mt -trng rui gim gm mt chui 12 allele, vi tnh tri gim dn t kiu di cho n trng t bin ln (w) theo th t t tri sang phi v trn xung nh sau:Allele Mu Allele Mu W+ di We eossin Wsat satsuma Wbl blood Wco coral Wap apricot Ww wine Wi ivory Wap3 apricot3 Wt tinged Wch cherry w white

Mt s gene ngi, chng hn nh cc gene i vi khng nguyn bch cu ngi HLA (human leukocyte antigen) xc nh cc khng nguyn trn b mt ca hu nh tt c cc t bo c th c nhiu allele. V d, gene HLA-B c nhiu hn 30 allele c xc nh khc nhau v mt khng nguyn trong mt s qun th. Kt qu ca s a dng ny l, trong mt qun th c rt nhiu kiu gene gene HLA-B (465 kiu gene khc nhau, vi 30 kiu ng hp v 435 kiu d hp), thc s to nn mt dy bin d kiu gene rng.

II. Tnh a hiu ca gene (pleiotropy)Hin tng mt gene nh hng n hai hoc nhiu tnh trng c gi l tnh a hiu (pleiotropy). V d, trong cc th nghim u H Lan,



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Mendel lu rng gene kim sot mu hoa tm v trng cng nh hng ln mu sc ht (v xm hoc nu) v gy ra s c mt hoc khng c mt ca cc vt mu tm b l. Trong v d allele kim sot lng vng chut ni trn, ta thy rng n cn nh hng ln sc sng cc th d hp v gy cht cc th ng hp. Nhiu bnh di truyn ngi gy ra bi cc gen c tc dng a hiu. Chng hn, bnh phenylxtn-niu (phenylketonuria = PKU) xy ra cc c th ng hp v allele ln . Nhng ngi mc bnh ny thiu hn enzyme cn thit cho s chuyn ha bnh thng ca amino acid phenylalanine thnh sn phm sinh ha k tip. Khi so snh cc c th bnh thng v PKU vi nhau cho thy mc phenylalanine nhm bnh cao hn nhiu. Ngoi ra, nhng ngi bnh cn c mt s bin i khc nh: ch s IQ thp hn, u b hn, v tc hi nht hn. Tt c cc hiu qu a hiu ny c th hiu nh l hu qu ca s ri lon sinh ha c s. Chng hn, cc bnh nhn PKU c s tch ly mt c t trong u khin cho b no b tn thng v dn ti IQ thp hn, u b hn. Mt v d khc v tnh a hiu ngi l bnh hng cu hnh lim (sickle-cell disease). Vy tnh a hiu gii thch trng hp ny nh th no? Nhng ngi ng hp v allele t bin ln ny (HbSHbS) ch to ra cc phn t hemoglobin bt thng, khin cho tt c cc t bo hng cu c dng hnh lim, kch thc b, mu nht (Hnh 2.5). Cc t bo hnh lim nhanh chng b c th ph hy v gy ra s thiu mu v suy yu c th ni chung. Ngoi ra,Hnh 2.5 Cc t bo hng cu bnh thng (trn) v dng hnh lim (di), vi phng i gn gp i ca hnh trn.

do hnh dng gc cnh m cc t bo hnh lim khng th vn chuyn trn tru trong mu v c xu hng tch t v gy tc nghn cc mao mch. Dng mu i n cc b phn c th b gim bt, gy st nh k, au n, v tn thng cc c quan khc nhau nh no b, lch, tim, thn...

III. Cc kiu tng tc gia cc gene khng alleleK t sau khi pht hin li cc nguyn l di truyn ca Mendel, xut hin nhiu cng trnh nghin cu trn cc i tng khc nhau, nh: b ng, u ngt, la m, ng, rui gim, g, chut, ch, nga...Mt s kt qu thu c t cc th nghim lai mt tnh cho thy t l phn ly khc vi cc t l 3:1 hoc 9:3:3:1. Cc trng hp cho t l phn ly 9:3:3:1



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hoc mt dng bin i ca n c l gii l do s tng tc qua li gia cc gene khng allele phn ly c lp. Tu trung c hai kiu tng tc gene, l: tng tc gia cc gen allele ( xt trn) v tng tc gia cc gen khng allele (thng c gi tt l tng tc gene). Do cc gene khng allele c th nm trn cng mt cp nhim sc th hoc trn cc cp nhim sc th tng ng khc nhau, cho nn v nguyn tc s c hai dng tng tc gene khng allele tng ng l tng tc c lp v tng tc lin kt; v dng sau phi l ch yu bi v s lng gene ca mt sinh vt nhiu hn s lng nhim sc th ca n rt nhiu. Tuy nhin, trn thc t, khi ni n s tng tc gia cc gene khng allele l ta mun ni ti s tng tc gia cc gene khng allele phn ly c lp. Lu : (1) S lng cc tnh trng hnh thnh nn mt c th sinh vt ni chung l nhiu hn s lng gene m ha protein c mt trong b gene ca n. Chng hn, theo c tnh gn y cho thy trong b gene ngi c khong 25.000 gene khc nhau trong khi c ti 50.000 loi protein thc hin tt c mi hot ng sng ca cc t bo. (2) Nh th, s biu hin ca a s tnh trng l kt qu ca s tng tc gia nhiu gene khc nhau trong qu trnh pht trin c th; v thc cht ca s tng tc l do s tng tc gia cc sn phm hot ng ca cc gen c bn cht protein hoc gia cc sn phm sinh ra t s xc tc ca cc enzyme. (3) Con ng chuyn ha mt cht c th trong t bo l mt chui gm nhiu phn ng sinh ha ni tip nhau m mi khu phn ng c xc tc bi mt enzyme (chng 7). Ngay c mt enzyme hay protein c cu trc bc bn cng gm mt s chui polypepetide thuc cc gene khc nhau to nn (chng 6). (4) cho n gin, thng thng ta gii thch cc kt qu tng tc bng hai gene nhng trn thc t, c th c nhiu hn hai gene cng quy nh mt tnh trng. Di y chng ta xt ba kiu tng tc gen chnh: Tng tc b tr, tng tc t ch v tng tc a phn cng gp. Cc v d nu ra di y l nhng th nghim kinh in ca di truyn hc. hiu c bn cht di truyn ca cc tnh trng , c bit l cc tnh trng mu sc, chng ta c gng lm sng t c ch sinh ha ca chng trong kh nng c th. 1. Tng tc b tr (complementary) Tng tc b tr l trng hp tng tc gene lm xut hin kiu hnh mi khi c mt ng thi cc gene khng allele trong mt kiu gene. Cc gene b tr c th l gene tri hoc gene ln ( trng thi ng hp). Tng tc kiu b tr biu hin di nhiu dng vi cc t l kiu hnh F2 khc nhau, nh 9:3:3:1; 9:6:1; 9:7.



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1.1. Tng tc b tr vi t l 9:3:3:1 V d kinh in cho trng hp ny l cc th nghim ca W.Bateson v R.C.Punnett v s di truyn hnh dng mo g. Khi lai gia cc ging g thun chng mo hnh hoa hng vi mo n (cn gi l mo hnh l) thu c F1 ton mo hoa hng, v sau khi cho tp giao F1 th F2 c t l phn ly 3 mo hoa hng : 1mo n. Tng t, khi lai gia cc ging g thun chng mo hnh ht u vi mo n, F1 gm tt c mo ht u v F2 phn ly 3 mo ht u : 1 mo n. Nhng khi lai gia hai ging g thun chng mo hoa hng v mo ht u, th F1 li thu c tt c c mo hnh qu c ch (hay ht h o) v t l phn ly F2 xp x 9 qu c ch : 3 hnh hoa hng : 3 hnh ht u : 1 mo n (hnh 2.6). Gii thch: Cc kt qu trong hai th nghim u cho thy cc dng mo hoa hng v ht u l tri so vi dng mo n. Kt qu sau cng cho thy F2 c 16 kiu t hp vi t l ngang nhau, trong khi F1 ng nht kiu gen (v b m thun chng); iu chng t F1 cho 4 loi giao t vi t l tng ng, ngha l d hp t v hai cp gene phn ly c lp. Suy ra tnh trng ny do hai gene khc nhau chi phi, ngha l tun theo quy lut tng tc gene. Mt khc, kiu hnh mi biu hin F1 v khong 9/16 F2 (ng vi s c mt ca c hai gene tri khng allele) phi l kt qu ca s tng tc gia cc gene tri khng allele theo kiu b tr. Quy c: Da vo t l phn ly kiu hnh F2 trong trng hp hai gene phn ly c lp v tn gi cc dng mo theo ting Anh (rose: hoa hng, pea: ht u), ta c

c ch: R-P-

hoa hng: R-pp

ht u: rrP-

mo n: rrpp

Hnh 2.6 Cc kiu mo c trng ca cc ging g khc nhau v cc kiu gene tng ng.

th quy c v kim chng n gin nh sau: R-P-: mo hnh qu c ch (do b tr gia cc gene tri R v P) R-pp: mo hnh hoa hng (do biu hin ca gene tri R) rrP-: mo hnh ht u (do biu hin ca gene tri P) rrpp: mo n (do khuyt c hai gene tri; kiu di) Kim chng: Ptc mo hoa hng (RRpp) mo ht u (rrPP) F1 mo qu c ch (RrPp)



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F1F1 = RrPp RrPp = (Rr Rr)(Pp Pp) F2 = (3R-:1rr)(3P-:1pp) = 9 R-P-: 3 R-pp : 3 rrP- : 1 rrpp = 9 c ch: 3 hoa hng : 3 ht u : 1 n Mt v d khc, l lai gia hai ging chut lng mu en vi mu v qu (cinnamon) c F1 ton chut lng mu xm (c dng "mui tiu" khi nhn gn, cn gi l agouti) v F2 cho t l 9 xm : 3 mu v qu : 3 en : 1 nu. Bn c th gii thch c s di truyn ca trng hp ny? 1.2. Tng tc b tr vi t l 9:7 V d: Th nghim ca Bateson v Punnett v s di truyn mu sc hoa cy u ngt (Lathyrus odoratus). T php lai gia hai ging hoa trng thun chng khc nhau, hai ng thu c F1 gm tt c cy lai c hoa mu ta (purple). Khi cho cc cy F1 t th phn F2 nhn c 382 hoa ta v 269 hoa trng; kt qu ny gn vi t l 9:7. Gii thch: Vi cch lp lun nh trn, ta d dng thy rng kiu hnh hoa ta l kt qu ca s tng tc b tr gia hai gene tri khng allele phn ly c lp. Trc khi i vo gii thch c s di truyn sinh ha ca cc kiu hnh, ta hy quy c v kim chng kt qu th nghim trn. Quy c: C-P- : hoa ta (do tc ng b tr gia cc gene tri C v P) C-pp, ccP-, ccpp : hoa trng (do khng c mt y c hai gene tri) Kim chng: Ptc ging hoa trng 1(CCpp) ging hoa trng 2 (ccPP) F1 hoa ta (CcPp) F1F1 = CcPp CcPp = (Cc Cc)(Pp Pp) F2 = (3C-:1cc)(3P-:1pp) = 9 C-P- : (3 C-pp + 3 ccP- + 1 ccpp) = 9 ta : 7 trng By gi ta th gii thch c s sinh ha ca cc kiu hnh. S hnh thnh mu hoa cy u ngt l kt qu ca s tng hp mt hp cht gi l anthocyanin; n xy ra thng qua mt chui cc khu chuyn ha c xc tc bi cc enzyme vn l sn phm ca cc gene. Nu nh bt k khu no trong qu trnh tng hp ny b gin on do vng mt ca mt enzyme hot ng th s hnh thnh mu sc khng xy ra. Mc d chi tit chnh xc ca s tng hp mu sc cy u ngt cn cha r, nhng c th minh ha bng m hnh tng qut hnh 2.7.


Tai lieu chia se tai: wWw.SinhHoc.edu.vnKiu gene c cha C Kiu gene c cha P Enzyme (C) Enzyme (P) Cht tin thn Sn phm trung gian Anthocyanin

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Hnh 2.7 S minh ha mi quan h gia cc gene tri C v P trong qu trnh hnh thnh sc t anthocyanin cy u ngt.

i vi cc kiu gene c cha c hai gene tri C v P (C-P-), c y cc enzyme cn thit cho vic to ra anthocyanin v do vy hoa c mu ta. Trong khi , kiu gene cha cc (ccP- hay ccpp), enzyme th nht khng c to ra hay khng c hot tnh; hu qu l, phn ng to sn phm trung gian khng thc hin c. Tng t, kiu gene cha pp (Cpp hoc ccpp) th phn ng th hai bin i cht trung gian thnh anthocyanin b dng li, v thiu hn mt enzyme tng ng. Ni cch khc, nu nh kiu gen c mang cp allele hoc l cc hoc l pp th con ng tng hp b gin on v cc sc t khng c to ra, v kt qu l hoa mu trng. 1.2. Tng tc b tr vi t l 9:6:1 V d: S di truyn hnh dng qu b ng. Khi lai hai ging b ng thun chng qu trn khc ngun gc vi nhau, F1 xut hin ton dng qu dt, v F2 c s phn ly kiu hnh xp x 9 dt : 6 trn : 1 di. Gii thch: Kt qu ny c th c gii thch theo mt trong hai cch sau: b tr gia cc gene tri hoc b tr gia cc gene ln. n gin, di y ta gii thch theo cch u, da trn quy c sau y: Quy c: D-F- : qu dt (do tng tc b tr gia cc gene D v F) D-ff v ddF- : qu trn (ch c mt trong hai gene tri D, F) ddff : qu di (do khuyt ng thi c hai gene tri) Kim chng: qu trn-1 (DDff) qu trn-2 (ddFF) Ptc F1 qu dt (DdFf) F1F1 = DdFf DdFf = (Dd Dd)(Ff Ff) F2 = (3D-:1dd)(3F-:1ff) = 9 D-F-: (3 D-ff + 3 ddF-) : 1 ddff = 9 qu dt : 6 qu trn : 1 qu di 2. Tng tc t ch (epistasis) Tng tc t ch l hin tng mt gene ny km hm s biu hin ca mt gene khc khng allele vi n. Gene t ch c th l tri hoc ln.



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2.1. t ch do gene ln vi t l 9:3:4 V d: S di truyn mu sc lng chut (hnh 2.8). Khi lai gia hai dng chut thun chng lng nu v bch tng, F1 xut hin ton chut lng en; v khi cho cc chut F1 tp giao vi nhau th F2 c s phn ly gn vi t l 9 en : 3 nu : 4 bch tng. gii thch kt qu ny, ta da vo bin lun nh v d u tin (mc III-1.1) v quy c sau y: Quy c: B-C- : en; bbC- : nu; B-cc v bbcc : bch tng Gii thch: T quy c ny, ta thy rng allele c khi trng thi ng hp (cc) c ch s biu hin ca B- v bb khin cho cc kiu B-cc v bbcc khng c sc t (bch tng, albino). i vi hai kiu hnh cn li c th gii thch theo mt trong hai cch sau: (1) Allele C l t bin tri, nn mt kh nng t ch v bn thn n khng to mu; khi allele tri B quy nh mu en l tri so vi allele b quy nh mu nu khi n trng thi ng hp; kt qu l B-C- c kiu hnh lng en v bbC- cho kiu hnh lng nu. Nh th y khng xy ra s tng tc b tr gia cc gene tri B v C. Cch l gii ny r rng l hp l. (2) Allele C quy nh mu nu v B l gene to mu, trong khi bb khng c kh nng . Do khi gene tri C (khng c kh nng t ch) ng ring s cho mu nu; cn ng chung vi gene tri B s cho hiu qu b tr tri vi kiu hnh mu en. R rng cch gii thch ny ch hp l trn hnh thc khi cho rng allele tri C xc nh mu nu.

Hnh 2.8 T tri sang l cc chut agouti en, agouti nu v bch tng.

Kim chng: Ptc Chut nu (bbCC) Chut bch tng (BBcc) F1 Tt c chut en (BbCc) F1F1 = BbCc BbCc = (Bb Bb)(Cc Cc) F2 = (3B-:1bb)(3C-:1cc) = 9 B-C-: 3 bbC- : (3 B-cc + 1 bbcc) = 9 en : 3 nu : 4 bch tng 2.2. t ch do gene tri vi t l 12:3:1 V d: S di truyn mu sc lng nga. Khi lai gia hai ging nga



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thun chng lng xm v hung vi nhau, F1 thu c ton nga lng xm. Sau khi cho tp giao cc nga F1 th F2 c t l kiu hnh xp x 12 xm : 3 en : 1 hung . Gii thch: gii thch kt qu ny, ta quy c: A-B- v A-bb : xm; aaB-: en; v aabb: hung . Theo , allele tri B quy nh mu en l tri so vi b- hung . V s d A-B- v A-bb cho kiu hnh lng xm trong khi chng c cha B v bb, bi v gene tri A t ch cc gene khng allele v ng thi n cn c kh nng to mu xm, cn allele a khng c c hai kh nng . iu ny c th hin qua s lai sau y: Ptc Nga xm (AABB) Nga hung (aabb) F1 Tt c nga xm (AaBb) F1F1 = AaBb AaBb = (Aa Aa)(Bb Bb) F2 = (3A-: 1aa)(3B-:1bb) = (9 A-B- + 3 A-bb) : 3 aaB- : 1 aabb = 12 xm : 3 en : 1 hung 2.3. t ch do gene tri vi t l 13:3 V d: S di truyn mu sc lng g. Khi lai gia ging g thun chng, g Leghorn trng vi g Wyandotte trng, F1 thu c ton g lng trng. Sau khi cho tp giao cc c th F1, F2 c t l phn ly kiu hnh xp x 13 lng trng (white): 3 lng c mu (colored). Gii thch: gii thch kt qu ny, ta quy c: I-C- , I-cc v iicc : trng; v iiC-: c mu. Theo , allele tri C - gene sn xut cht to mu (chromogen) l tri so vi allele c- khng c kh nng to mu; v allele tri I (inhibitor) t ch gene khng allele vi n v n cng khng c kh nng to mu, cn allele i khng c kh nng t ch ln to mu. S lai: Ptc G Leghorn trng ( IICC ) G Wyandotte trng (iicc) F1 Tt c g trng (IiCc) F1F1 = IiCc IiCc = (Ii Ii)(Cc Cc) F2 = (3I-:1ii)(3C-:1cc) = (9 I-C- + 3 I-cc + 1 iicc) : 3 iiC= 13 trng : 3 c mu 3. Tng tc cng gp - s di truyn a gene v cc tnh trng s lng 3.1. Tng tc cng gp (additive) Tng tc cng gp hay s di truyn a gene (polygenic) l hin tng di truyn c trng ca mt s tnh trng s lng (quantitative trait), trong cc gene khng allele tc ng cng hng ln s biu hin ca mt tnh trng. Mi allele (thng l tri) ca cc gene a phn nh



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th ng gp mt phn ngang nhau trong s biu hin ra kiu hnh mt mc nht nh. Nh vy, liu lng cc allele tng dn trong cc kiu gene s to ra mt dy bin d kiu hnh lin tc trong qun th. V d: Cc th nghim ni ting nm 1909 ca nh di truyn hc Thy in (Sweden) Herman Nilsson-Ehle v s di truyn mu sc ht la m (ht y tc l phi nh - kernel). Khi lai gia cc ging la m thun ch

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