DI TRUYN N GEN TRN

NHIM SC TH THNG

MC TIU
1. Phn tch c cc c im di
truyn ca kiu di truyn n gen
nm trn NST thng
2. Trnh by c cc yu t nh hng
n kiu di truyn cc gen t bin
trn NST thng.

CC KHI NIM C BN
KHI NIM V KIU GEN V KIU HNH
1. Kiu gen (genotype)
2. Kiu hnh (phenotype)
3. Tri ln
4. Quy tc xc sut

CC KHI NIM C BN
XC SUT
L t l xut hin mt s kin nht nh trong
mt lot cc s kin
1. Quy lut nhn

c=axb
2. Quy lut cng

c=a+b

CC KHI NIM C BN
XC SUT

Aa

Aa

A: a

AA
AA

A: a

Aa
Aa

Aa
Aa

AA : Aa : aa

aa

CC KHI NIM C BN
XC SUT

AA

Aa

Aa

aa

CC KHI NIM C BN
NGUY C TI PHT V NGUY C XY RA
Kh nng sinh con mc bnh

Cp v chng c
con mc bnh

Cp v chng cha
sinh con

Nguy c ti pht
(Recurrence risk)

Nguy c xy ra
(Ocurrence risk)

PH H (PEDIGREE)
Ph h l cng c ph bin trong di truyn y hc. S
dng cc k hiu n gin minh ha mi lin h
gia cc thnh vin trong gia nh v cho thy nhng
thnh vin no trong gia nh mc hoc khng mc mt
bnh di truyn no .

PH H (PEDIGREE)

Mi tn c s dng ch i
tng u tin c kho st

PH H (PEDIGREE)

PH H (PEDIGREE)

PH H (PEDIGREE)
T l mc bnh gia nam v n?
Cp v chng no c kh nng sinh
con mc bnh?
C s gin on gia cc th h
hay khng?
D on kiu di truyn ca bnh.
Kiu gen ca cc thnh vin.
S dng cc quy tc xc sut
tnh t l mc bnh.

DI TRUYN GEN TRI TRN NHIM

SC TH THNG
Tn s bnh di truyn gen tri trn NST thng
vo khong 1/200
Tn s ca tng bnh di truyn gen tri ring l
trn NST thng rt him

< 1/1000

DI TRUYN GEN TRI TRN NHIM

SC TH THNG

Bnh xut hin c 2 gii vi t l xp x

Khng c s gin on gia cc th h
B m c ngi b bnh th c kh nng
Hn nhn ph bin lm xut hin bnh:
sinh con b bnh
C b hoc m b bnh (Aa x aa)
B m khng b bnh th sinh con khng

DI TRUYN GEN TRI TRN NHIM

SC TH THNG

Nguy c sinh con mc bnh l

50%

DI TRUYN GEN TRI TRN NHIM

SC TH THNG

DI TRUYN GEN TRI TRN NHIM

SC TH THNG
C IM
1. T l mc bnh xp x c 2 gii
2. Khng c s gin on gia cc th h
3. Ngi mang gen bnh trng thi d hp kt
hn vi ngi mang gen bnh thng s truyn
gen bnh v gy bnh cho mt na s con ca
h.
4. Nu b m khng mc bnh th con ca h s
khng mc bnh, tr khi xut hin t bin mi.

DI TRUYN GEN TRI TRN NHIM

SC TH THNG
Bnh lon sn sn bm sinh (Achondroplasia)
t bin gene FGFR3 nm trn
NST 4, di truyn kiu tri trn
NST thng
Protien FGFR3: l mt receptor ca enzyme
tyrosine kinase trn mng t bo gn vi
cc yu t pht trin fibroplast (fibroplast
growth factors).

c im
Ln
Cc t bin gene mi lin quan n
s gia tng tui ca b (trn 35 tui).

DI TRUYN GEN TRI TRN NHIM

SC TH THNG

DI TRUYN GEN LN TRN NHIM

SC TH THNG

Nhiu th h khng c biu hin bnh

T l mc bnh nam v n xp x nhau
Hn nhn ph bin dn n sinh con
mc bnh l: Aa x Aa

DI TRUYN GEN LN TRN NHIM

SC TH THNG
Kiu hn
nhn

Rr x Rr

Nguy c ti pht
hay nguy c xy
ra

25%

DI TRUYN GEN LN TRN NHIM

SC TH THNG
Kiu hn
nhn

rr x rr

Nguy c ti pht
hay nguy c xy
ra

100%

DI TRUYN GEN LN TRN NHIM

SC TH THNG
Kiu hn
nhn

Rr x rr

Nguy c ti pht
hay nguy c xy
ra

50%

DI TRUYN GEN LN TRN NHIM

SC TH THNG
Kiu hn
nhn

Rr x RR

50%

con sinh ra bnh

50%

con sinh ra mang gen

thng

DI TRUYN GEN LN TRN NHIM

SC TH THNG
C IM
1. T l mc bnh xp x c 2 gii
2. Bnh thng c thy mt hoc mt s anh
ch em rut, nhng khng xy ra cc th h
u.
3. 25% s con ca cp v chng mang gen bnh
trng thi d hp (Aa x Aa) s biu hin bnh.
4. Tnh trng hn nhn ng huyt thng c
gp trong ph h ca cc bnh di truyn ny
nhiu hn so vi cc bnh di truyn khc

DI TRUYN GEN LN TRN NHIM

SC TH THNG
Bnh bch tng
bin gene
gene m
mha
hachocho
t bin
enzyme tyrosinase
enzyme ha
tyrosinase
chuyn
chuyn
tyrosine
thnhha
melanine nm trn
tyrosine
melanine
NST
11 (lthnh
mt yu
t tham nm
gia cu to sc t da,
trn
NST
11 (l mt yu t tham
tc v
mt)
gia cu to sc t da, tc v
mt)

DI TRUYN GEN LN TRN NHIM

SC TH THNG
Bnh bch tng

CC YU T NH HNG N
KIU DI TRUYN
T BIN MI
Tre c sinh ra vi mt bnh di
truyn va trong gia nh cua tre
cha h co tin s v bnh

Kt qua cua mt t bin mi

Bnh di truyn do gen tri trn
NST thng
Nguy c ti pht khng cao hn mc
chung ca qun th (HC Marfan:
1/10000)
Cc bnh di truyn gen tri thng l

CC YU T NH HNG N
KIU DI TRUYN
TNH TRNG KHM CC T BO
DNG SINH DC
B me co ti 2 con hoc nhu hn mc
cung mt loai bnh di truyn tri NST
thng nhng tin s khng ai mc bnh

Hin tng kham cua cac

t bao dong sinh duc
t bin giai on sm trong thi k phi t bo mm sinh
dc ca b hoc m.
Khng nh hng hoc ch nh hng n mt vi t bo soma
Truyn cho con th h sau

CC YU T NH HNG N
KIU DI TRUYN
KHI BNH MUN
Nhiu bnh di truyn phi ch n giai on trng
thnh mi biu hin

HU QU
Co con trc khi ho bit tnh
trang mang gene bnh cua mnh.
Giam vai tro cua hn tng chon
loc
Kho khn trong vic suy oan kiu
di truyn cua bnh

CC YU T NH HNG N
KIU DI TRUYN
KHI BNH MUN

Phn b tui khi bnh cua bnh Huntington

Triu chng cua bnh thng khng biu hin
trc tui 30 hoc mun hn

CC YU T NH HNG N
KIU DI TRUYN
KHI BNH MUN

CC YU T NH HNG N
KIU DI TRUYN
TNH THM GIM
Ngi mang kiu gen ca bnh nhng khng biu
hin trn kiu hnh nhng vn truyn gen bnh
cho th h sau.
V d: Tnh thm 100%: 100% b bnh
Tnh thm 80%: 80% b bnh, 20% khng b bnh

C CH

Gi thuyt Two-hit

Hin tng methyl ha

CC YU T NH HNG N
KIU DI TRUYN
TNH THM GIM
Bnh u nguyn bo vng mc: Tnh thm 90%

CC YU T NH HNG N
KIU DI TRUYN
BIU HIN A DNG

Bnh co th co tnh thm hoan toan

nhng mc nghim trong cua bnh
co s thay i rt ln

Tao iu kin cho gene bnh khng b

ao thai va
co mt vi tn s cao trong qun th.

CC YU T NH HNG N
KIU DI TRUYN
BIU HIN A DNG

Bnh u x thn kinh

CC YU T NH HNG N
KIU DI TRUYN
TNH A HIU (pleiotropy)
Mt gen c th gy nhiu hiu qu khc nhau trn c
th th c gi l gen a hiu
Hi chng Marfan do cc t bin trn gene FBN1 nm trn
NST 15, m ha cho mt glycoprotein gi l fibrillin-1, mt
thnh phn trong hn dch ngoi bo

Lch thuy tinh th (Lens subluxation)

DI TRUYN GEN LN TRN NHIM

SC TH THNG
Bnh x nang (CF: Cystic Fibrosis)
T l M: 1 / 2,500 tr
Chu (Hawaii): 1 / 90,000 tr

Nguyn nhn
t bin gene CFTR, nm v tr
7q31, c chiu di 250 kb vi 27 exon.
Gen ny m ha cho protein CFTR
iu ha hot ng ca knh Cl nm
trn bn mt mng t bo biu m
dn n vic hnh thnh cc x nang
ti cc c quan trong c th: phi,
gan, ty, ...

DI TRUYN GEN LN TRN NHIM

SC TH THNG
PHI: Tc nghn v nhim trng ph qun
gy
cn Tc
tr h
hp.cc
L nguyn
GAN:
nghn
ng mtnhn
nh,gy
gycht
nh
hng
un
cachc
bnhnng
x nang
hng
tiu ha v gy mt
TY:
cc ng
dn ty5%
dnbnh
n
chc Tc
nngnghn
ca gan
khong
gim
cc
enzyme tiu ha, gp 65%
nhn b
x nang
RUT:
C th
gy tc
lngn
rutbnh
i
bnh nhn
x nang.
C rut,
th dn
hi
phu thut 10% tr s sinh mc
tiuphi
ng.
bnh
x nang.
C QUAN
SINH DC: C th dn n v
sinh c nam v n.

TUYN M HI: Do bt thng knh

Cl- nn dn n nng mui trong m
hi tng qu mc. nh lng nng
chlorid trong m hi l mt c s n
chn on bnh x nang.

CC YU T NH HNG N
KIU DI TRUYN
TNH D NGUYN (heterogenity)
1. D nguyn v locus (locus heterogenity)
Khi mt bnh c gy ra bi cc t bin cc
locus khc nhau nhng gia nh khc nhau th
c gi l tnh d nguyn v locus.
2. D nguyn v allele (allelic heterogenity)
Khi cc t bin trn cng 1 gen trn cng locus
gy nn nhng bnh khc nhau trn nhng c
quan khc nhau th c gi l d nghuyn v
allele.

CC YU T NH HNG N
KIU DI TRUYN
D nguyn v locus (Locus heterogenity)
Bnh thn a nang ngi trng thnh
(Adult polycystric kidney disease: APKD)
Bnh di truyn gene tri trn NST thng gy ra
s tch luy dn cac nang thn. Bnh nhn co
th phat trin nang gan, cao huyt ap, khuyt
tt cua cac van tim, phnh mach mau nao.

t bin gen xy ra trn NST 16 (PKD 1)

Thn bnh
hoc trn
thng

a nang
NST sThn
4 (PKD
2)

CC YU T NH HNG N
KIU DI TRUYN
D nguyn v allele (allelic heterogenity)
t bin gen RET m ha cho receptor
tyrosine kinase

Bnh Hirchsprung

Ung th tuyn gip v

Gim nhu ng rut

tuyn thng thn

v to bn mn tnh

CC YU T NH HNG N
KIU DI TRUYN
KHI BNH SM V GIA TNG MC
BIU HIN TH H SAU
Bnh loan dng c
(DM1)
Gene gy bnh
madystrophy)
hoa cho
(myotonic

enzym protein myosin kinase nm

trn NST 19
t bin gy bnh xay ra do
s
gia
tng
oan
lp
trinucleotide CTG nm trong
vung 3' khng giai ma cua gene
S lng cac oan lp nay
lin quan cht che n mc
nng nhe trong biu hin
bnh.

CC YU T NH HNG N
KIU DI TRUYN
KHI BNH SM V GIA TNG MC
BIU HIN TH H SAU

Bnh loan dng c

(DM1)
(myotonic dystrophy)
Ngi khng mc bnh:
5 - 30
oan lp
Ngi co biu hin bnh nhe
hoc khng co triu chng: 50 100 oan lp
Ngi b loan dng c: t 100 hang ngan oan lp

CC YU T NH HNG N
KIU DI TRUYN
KHI BNH SM V GIA TNG MC
BIU HIN TH H SAU

Bnh loan dng c

(DM1)
(myotonic
Nhe - co th
ch dystrophy)
co uc thuy tinh
th va yu c nhe, tui tho bnh
thng
Kinh in - yu va teo c, uc thuy
tinh th, khim khuyt dn truyn
cua tim, khi bnh luc v thanh
nin, co th b giam tui tho.
Bm sinh - giam trng lc nng
va yu khi sinh, thng co chm

CC YU T NH HNG N
KIU DI TRUYN
Bnh loan dng c
(DM1)
(myotonic dystrophy)

CC YU T NH HNG N
KIU DI TRUYN
Bnh loan dng c
(DM1)
(myotonic dystrophy)

HT