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06 LE THANG

Giao tr'inhDl TRUYiN HOC

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GIAO TRINHDITRUYEN HOC

(Dung cho cac trucmg Dai hoc, Cao dang chuyen nganh Sinh hoc,Cong nghe Sinh hoc, Y te, Nong, Lam nghiep)

(Tai ban Ian thu: hai)

DAI HOC THAI NGUYEN

TRUNG TAM HOC LIEU • •

n h A x u a t b a n g i Ao d u c

Ban quyen thuoc H E V O B C O - Nha xuat ban G iao due.

04 - 2008/CXB/421 - 1999/GD Ma so: 7K686y8 - DAI

l 6 i n o i d a u

Trong suot the ky XX, Di truyen hoc da xuat hien va n hanh chong p ha t trien de trd th&nh mot trong nhiing mon khoa hoc trung tarn cua Sinh hoc. Ke tijf khi cac quy luat Mendel difdc p h a t hien lai vao nam 1900, Di truyen hoc da co nhiing biicic tien nhanh chong trong cong cuoc tim kiem ban chat phan tif cua vat chat di truyen. Vao nhiing nam 1950, J am e W atson va Francis Crick da kham pha cau true chuoi xo&n kep cua phan tut ADN m ang thong tin di truyen va si1 kien khoa hoc quan trong la viec hoan ta t giai ma he gen ngifdi vao nam 2001... Hien nay di truyen hoc da co trong tav nhiing phifdng tien hiiu hieu de phan tich gen, he gen va bieu hien cua gen trong cac he thong sinh hoc. Nhiing kien thijfc di truyen hoc difdc bo sung n hanh chong. Nhiing th an h tifu cua Di truyen hoc ngay cang mang lai nhiing ldi l'ch to 16n cho ddi song con ngifdi.

De giup s inh vien cao dang, dai hoc chuyen nganh sinh vat, cong nghe sinh hoc va cac thay co giao giang day mon Sinh hoc d triidng pho thong nam viing difdc cackien thilc cd ban va cap n h a t vdi cac kien thiic m6i cua Di truyen hoc, chung toi da biensoan cuon giao tr in h nay.

Giao tr in h chia lam 3 phan, gom 18 chiidng:P h a n M ot: Di truyen hoc cd set Chitdng I. Cac quy luat MendelChiidng II. Gen, nhiem sac the va cd che cua cac quy luat MendelChitdng III. Cac gen da alen va sit tiidng tac genChiidng IV. Lien ket gen va lap ban do gen d sinh vat nhan chuanChiidng V. Cac phiidng phap khac de lap ban do di truyenChiidng VI. Di truy in hoc cac tinh trang soliidngChiidng VII. Di truyen ngoai nhanChiidng VIII. Di truyen hoc vi khudn va virutP h a n H ai: Di truy in hoc phan titChiidng IX. A D N : Cau true va sii sao chepChiidng X. Cau true cua nhiem sac the nhan sd va nhan chuanChiidng XI. Phien ma, dich ma va ma di truyinChiidng XII. Cac ky thuat dung trong nghien ciiu di truy in phan tiiChiidng XIII. Dieu hod bieu hien cua genP h a n Ba: S ii bien doi gen, he gen va tien hodChiidng XIV. Dot bien gen va sii a chiia dot bien genChiidng XV. Dot bien soliidng va cau true nhiem sac theChiidng XVI. Cac yeu to di truyin van dong,Chiidng XVII. Di truyin hoc quan the va tien hod Chiidng XVIII. Cd sd di truy in hoc benh ung thiiMac du da h e t siic co" gang trong qua tr inh bien soan, song chac chan van con co

th ieu sot. C hung toi mong nh an difdc cac y kien dong gop cua cac ban doc de cuon sach difdc hoan th ien hdn. Moi gop y xin giii ve Cong ty Co ph an sach Dai hoc - Day nghe, N ha Xuat ban Giao due 25, H an Thuyen, H a Noi.

Tac g ia

MUC LUC• *

PMn Mot: DI TRUYEN HOC CO SCJ

Chirang I. Cac quy luat Mendel......................................................................................................................... 71.1. Mendel phat hien cac quy luat di truyen...................................................................................................... 71.2. Sir dung xac sua't va phep thtr khi-blnh phuong de danh gia s6 lieu thi nghiem ............................. 121.3. Can cac bien di di truyen d£ nghien ctiru di truyen hoc.........................................................................141.4. Cac quy luat Mendel co nhi£u ting dung thuc te'...................................... ...... ....................................... 15Chuong II. Gen, nhi£m sac the va co che cua cac quy luat M endel.....................................................192.1. Tam quan trong cua chu trinh te bao va tap ti'nh nhiem sac the trong nghien curu di truyen hoc.......192.2. Giam phan la ccf so cua cac quy luat M endel.................................... ..................................................... 242.3. Su di-truyen lien ke't gioi ti'nh cung la bang chting khang dinh thuyet di truyen nhiem sac th£ 33Chuong III. Cac gen da alen va sir tuong tac g e n ......................................................................................393.1. Cac alen co nhieu bien dang........................................................................................................................393.2. He thong phan loai theo chiic nang cho cac alen dot bien cua H. J. Muller............................................ 423.3. Sir tuong tac gen lam thay d6i ty le phan ly cua cac phep lai hai ti'nh...............................................43Chuong IV. Lien ket gen va lap ban do gen o sinh vat nhan chuan................................................... 474.1. Tai t6 hop la co so de lap ban do gen.^........................................................ .-......................................... 474.2. Lap ban do gen tao ra ban d6 nhiem sac the theo trat tir thang.............................................................51Chtong V. Cac phuong phap khac de lap ban do di truyen.................................................................. 575.1. Dung phan rich bo bon de lap ban do nhiem sac th e..............................................................................575.2. Lap ban d6 gen bang cac phuong phap khac......................................................... ................................. 625.3. Lap ban d6 cau true tinh vi cua gen...........................................................................................................67Chuong VI. Di truyen hoc cac tinh trang so luong............................................................................................716.1. Cac tmh trang so' luong di truyen theo kieu Mendel...............................................................................716.2. Sir dung tho'ng ke de phan tich su di truyen cac ti'nh trang so luong...................................................736.3. Sir dung he so' di truyen de tien doan kieu hinh doi con ........................................................................80Chuong VII. Di truyen ngoai nhan.....................................................................................................................847.1. Cac gen cua me co the tac dong den kieu hinh cua con........................................................................ 847.2. Ty the va lap the co nhiem sac the rieng.................................................................................................. 867.3. Cac tac nhan lay nhiem co the di truyen duoc........................................................................................ 89Chuong V m . Di truyen hoc vi khuan va virut......... 928.1. Vi khuain de nuoi cay va co nhieu dot bien..............................................................................................928.2. Tiep hop can su tham gia ciia plasmid......................................................................................................938.3. Bien nap la lay ADN vao te bao............................................................................................................ 1018.4. Di truyen hoc phage va nghien curu hien tuong tai nap b6 sung them nhieu thong tin ve gen......... 1028.5. Tai nap rat hiru l'ch de lap ban d6 cac gen lien ket gan................................................................... 107

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PMn Hai: DI TRUYEN HOC PHAN TIT Chirofng IX. ADN: Cau true va su sao chep.................... ..................................................................... 1119.1. Cac nha khoa hoc tim ra cac bang chung chumg minh ADN la vat chat di truyen.................... 1119.2. Ban chat hoa hoc cua ADN va ARN................................................................................... ............... 1139.3. ADN dung chi'nh no lam khuon miu de’ sao chep ........................................... ................................ 1189.4. ADN virut va ADN plasmid sao chep theo kieu vong lan.............................................................. 126Chuong X: Caiu true phan tu cua nhi£m sac the nhan so va nhan chuan................................................. 12710.1. Nhiim sac the nhan so duoc bao goi trong khong gian hep........................................................ 12710.2. Nhi6m sik the nhan chuan co trinh tu phirc tap...................................... ......................................... 12910.3. Nhidm sac the nhan chuain xoan rat chat........................................................................................... 13110.4. Cac nhiSm sac the nhan chuan co nhung viing biet hoa....................................................................134Chuong XI. Phien ma, dich ma va ma di truyen...........................................................................................14011.1. Cac protein xac djnh kieu hinh cua sinh vat....................................................................................... 14011.2. Phien ma la su truyen thong tin tu ADN sang ARN..........................................................................14211.3. Cac sinh vat nhan chuan sua d6i mARN sau phien m a.................................................................... 14711.4. Trinh tu mARN duoc dich thanh trinh tu cac axit amin................................................................... 15011.5. Ma di truygn kha don gian......................................................................................................................155Chuong XII. Cac ky thuat dung trong nghien curu di truyen phan tu .........................................................15912.1. Cac ky thuat chuan hoa de’ tach dong gen............................................................................................15912.2. Cac phuong phap do tim gen trong thu vien gen ................................................................................16512.3. Nghien cun cac gen tach dong de’ thu nhan cac thong tin co ban ve gen.......................................16812.4. Cac vecto tach dong dac b iet.................................................................................................................17212.5. Hien tuong da hinh cac doan trinh tu ADN la dau chuan di truyen huu l'ch................................ 17312.6. Tach dong cac doan ADN kfch thudc Ion............................................................................................17512.7. Nghien curu trinh tu cac he gen cho thay nhieu dieu ly thu.............................................................. 17712.8. Gen tach dong co nhieu ung dung.................................................................................................... 179Chuong XIII. Dieu hoa bieu hien cua g en .............................................................................................18013.2. Mo hinh dieu hoa phien ma operon la c ............................................................................................... 18113.3. Mo hinh dieu hoa phien ma bang su phien ma do va su chong ket thiic phien m a..................... 18413.4. Hoat dong cua gen co the duoc didu hoa o muc do sau phien m a..................................................189

Phan Ba: SUBIEN DOI GEN, HE GEN VA TIEN HOA........................................Chuong XIV. Dot bien gen va sua chua dot bien gen.................................................................................... 19214.1. Phan loai dot bien g en ............................................................................................................................ 19214.2. Cac dot bien ngau nhien la do cac nhan to tu nhien gay ra..............................................................19314.3. Cac dot bien cam ung la do tac dong cua cac nhan to moi truong...................................................19714.4. Cac co che sinh hoc sua chua dot bien............................................................................................... 203Chuong XV. Dot bien so luong va cau true nhidm sac the......................................... ........................20615.1. Da boi th e ................................................................................................................................................. 20615.2. Di boi the’ .................................................................................................................................................. 20815.3. Dot bien cau true nhiem sac the’........................................................................................................... 210Chuong XVI. Cac yeu to di truyen van dong............................................................. ...................................21616.1. T6ng quan ve cac yeu to di truyen van dong................................. ................................................... 21616.2. Cac yeu to di truyen van dong a vi khuain.......................................................................................... 217

16.3. Cac yeu to di truyen van d6ng a sinh vat nhan chu£n........................................................................22016.4. Gen nhay sao chep nguoc (retrotransposon)............................... ........................................................22316.5. Cac yeu to di truyen van dong a nguai.................................... ........................................................... 224

16.6. Y nghla di truy^n'hoc va tien hoa cua cac y£u td di truyen van ddng............................................225Chuong XVII. Di truyen hoc quan the va tien hoa....................................................................- ............... 22717.1. Su xuat hien cua thuyet ti£n hoa va di truydn hoc qu£n th£......................... .................................22717.2. Tan so alen va trang thai can bang di truyen cua qu2n the...............................................................22817.3. Chon loc tu nhien..................................................................................................................................... 23517.4. Hien tucfng lac dong di truy6n (Random genetic drift)..................... ...............................................23917.5. Cac trang thai can bang trong cac quan the tu nhien........................................................................ ^4017.6. Su hinh thanh loai......................... .......................................................................................................... 24317.7. Su tien hoa cua loai nguai........................................................................................ ............................. 245Chuong XVIII. Co so di truyen hoc benh ung thu.................................................................................24818.1. Ung thu co co so di truyen....................................................................................................................-24818.2. Oncogen........... ............................................ ................................................ ..........................................z18.3. Cac gen uc che khoi ............................................................................................................... .............Tai lieu tham khao......................................................... .............................................. ................................255

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Phan Mot

DI TRUYEN HOC C0 Sflf

CHUONGI

CAC QUY LUAT MENDELI

«1.1. Mendel phat hien cac quy luat di truyen

Nam 1866, Mendel cong bo' ket qua cac thu nghiem lai tren cay dau H a Lan Pisum sativum , trong do mo ta hai nguven ly dieu khien sii di truyen cua cac tinh trang. T hanh cong ma Mendel co difdc la nhd phifdng phap nghien ctfu dung dan cua ong. Trifdc het, vdi nhieu nam kinh nghiem n h a n giong thvfc vat, ong da chon cay dau vifdn lam do’i tifdng th i nghiem vi do la cay til thu phan nghiem ngat, nhd do co the tao ra cac dong th u a n va de dang kiem soat cac phep lai. Thil hai, trong cac phep lai cua minh, ong chi chon theo doi mot, hoac mot vai t inh tra n g qua cac the he, dieu ma cac » nha nghien cOfu trifdc do mac sai lam. Cuoi cung, ong da phan tich ky lifdng ve m at toan hoc cac ket qua th i nghiem thu difdc.

1.1.1. Cac th i nghiem lai mot tinh cua M endel cho thay cac gen phan lyMendel da tien h a n h 7 phep lai giufa cac dong dau th u a n chung m ang cac cap tinh

trang tifdng phan - cac dac diem co hai t ran g thai bieu h ien khac nhau . Do la cac tinh tran g m au sac h a t (vang va xanh), h inh dang h a t (trdn va nhan), m au s&c vo qua tifdng ling vdi m au hoa (xam co diem cac cham tim, hoa tim va vo qua tr^ng, hoa

■ tr in g ) , h inh dang vo qua (vo qua cang phong va vo qua xep). m au s^c qua khi chifa chin (xanh va vang), vi tr i hoa moc so vdi than (d nach hoac ngon), chieu cao cay (cao va thap). Cac phep lai deu cho cac ket qua giong nhau d F l va F2.

Vi du. khi lai cac cay th u a n chung h a t trdn vdi cac cay th u a n chung h a t n h a n ong thu difdc toan bo con lai F l co h a t trdn. M endel goi cac t in h t ra n g difdc bieu hien ra d F l la cac t in h t ra n g troi, con tinh tran g kia la lan. Khi cho cac cay F l tif th u phan. ong th u dude F2 co ty le phan ly 3 trdn : 1 nhan . O ng tiep tuc cho F2 tif th u phan de th u F3. Ket qua cho thay. cac h a t F2 m ang t in h t ra n g lan la th u a n chung (sinh ra cac h a t nhan ), cac h a t F2 m ang t inh t ra n g troi co hai loai: 1/3 th u a n chung (sinh ra h a t trdn), 2/3 s inh ra F3 v6i ty le 3:1. Ket qua th i ngh iem cua M endel difdc tr inh bay d bang 1.1.

De giai thich cho cac ket qua thi nghiem th u difdc, M endel gia th ie t rSng. cac tinh tran g tifdng phan nhif h a t trdn, n h an do cac nhan to di truyen , ma ngav nay chung ta

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biet do la cac gen", quy dinh. Mendel cho rang cac gen nay co the ton ta i d cac tran g tha i khac n h au (ngay nay chung ta goi la cac alen) nen co the cho ra cac kieu hinh khac nhau. Vi du, t inh tra n g hinh dang h a t do mot gen quy dinh. nh iing gen nay ton ta i d hai t ra n g th a i alen. Dong th u an h a t nh an do Mendel tao ra chi co mot alen cua gen nay (ky hieu la r), con dong t h u i n h a t trdn lai m ang alen khac ( R ).

Bang 1.1! Ket qua mot so phep lai mot tinh cua Mendel

Bo me F1 F2 Ty le phan ly F2

Cay cao x cay thap Cao 787 cao : 277 thap 2,84 : 1

Hoa moc nach x hoa ngon Nach 651 nach : 207 ngon 3,15 : 1

Qua xanh x qua trang Xanh 428 xanh : 152 vang 2,82 : 1

Qua phong x qua xep Phong 882 phong : 299 xep 2,95 : 1

Hat xanh x hat vang Vang 6022 vang : 2001 xanh 3,01 : 1

Hat tron x hat nhan Tron 5474 tron : 1805 nhSn 2,96 : 1

Vo qua xam x vo trang Xam 705 xam : 224 trang 3,15 : 1

Trifdc khi thao luan cac giai thich cua Mendel, chung ta hay lam quen vdi mot so khai niem. M endel cho ran g moi cay dau m ang hai b an sao (hai alen) cua m ot gen. Ca the dong hdp tit ( hay con goi la the dong hdp tit) co hai alen giong nhau . N hli vay, cay dau th u a n chung h a t nh an la dong hdp tii ve alen quy dinh h a t n h a n (rr) va cay th u a n chung h a t trdn la dong hdp tif ve alen quy dinh h a t trdn (RR). Ca the di hdp tit (hay the di hap tit) m ang hai a len khac n h a u (Rr). M endel cung cho rang , moi cay chi truyen mot alen cho ddi con qua cac the he. Nhif vay moi ca the difdc di t ru y e n mot a len tii bo, mot alen tif me. Cac cay F l thu difdc trong phep lai cay dong hdp ti’i h a t t rdn (RR) vdi cay dong hdp tif h a t n h an (rr) se la di hdp tijf Rr. Kieu h inh cua ca the la sii b ieu hien cua tinh t ra n g m a ta q u an sa t diidc (vi du, h a t la trdn hoac nhan). Kieu gen cua ca the la cau true di truyen cua no (vi du, RR, rr hoac Rr). T inh t ra n g bieu h ien ra d F l khi lai bo' me th u a n chung co k ieu h inh khac n h au ve t in h t ra n g do diidc goi la t inh t ra n g troi, con tinh t ra n g k ia la lan. Alen quy dinh kieu h inh troi la a len troi, a len quy d inh kieu h inh lan la alen lan. Cac alen cua mot gen diidc bieu dien bang cung mot chu cai. Alen troi difdc bieu dien bang chii in hoa. con alen lan diidc bieu d i in bang chu thiidng.

Mendel cho rang, cac alen khong bi hoa tron trong the di hdp tii. Bang chiing cho gia thuye t do la k ieu h in h lan lai xua t h ien trd lai khi lai cac the di hdp tii. Xgoai ra, hai alen con tach n h a u ra trong qua tr in h hinh th a n h giao tii. Dieu do co nghia la cac cay dau di hdp tif (Rr) se sinh ra hai loai giao tif. mot loai m ang alen R. loai kia m ang alen r ma khong the co loai nao m ang ca hai alen; t ru n g binh se co 1/2 so' giao tu m ang alen R va 1/2 so giao tif m ang alen r. T a t nhien, cac the dong hdp tii RR va rr chi s inh ra mot loai giao tii. Gia th ie t cua Mendel rang cac a len tach n h a u ra trong qua tr inh h inh th a n h giao tii diidc goi la quy luat phan ly hoac quy lu a t thil n h a t cua Mendel. Quy lu a t do diidc sii dung de giai thich cho cac ket qua th i ngh iem lai mot tinh cua Mendel nhii sau (hinh 1.1):