???????????????????????p53(???????

1
???
?10? ????????????
?? ?
2
????
?????????????????
?????????????????????????????????
?4??????????????????????????????????????(????)????
?
3
????
??????????????????????????????????????????????????
???????????????????????p53(??????? ???????????)???
????DNA???????????????
4
????
???????????????????????????????????????????
????????????????????????????????????sickle cell
anemia??????
5
???????
??????????????????????????????????????????????????
????????????????????
??????????????????????????????????
6
???????
????????????????(??????)??????????????????????????
?????????????????
?????????????????????????????????
7
???????
??????????????????????????????????????????????????
????????????????????????????????????????
8
????????
????????????????????(O2?????)????????(oxy)???????
???????????????????(deoxy)???????????????
9
????????
????????a?????ﾟ??????????2????????????
a?????ﾟ????????????(????????)???????????????????
10
a???????
1 2 3 4 5 6 7 8
9 10 11 12 13 14 15 1 Val
Leu Ser Pro Ala Asp Lys Thr Asn Val Lys Ala Ala
Trp Gly 15 16 Lys Val Gly Ala His Ala Gly
Glu Tyr Gly Ala Glu Ala Leu Glu 30 31 Arg
Met Phe Leu Ser Phe Pro Thr Thr Lys Thr Tyr Phe
Pro His 45 46 Phe Asp Leu Ser His Gly Ser
Ala Gln Val Lys Gly His Gly Lys 60 61 Lys
Val Ala Asp Ala Leu Thr Asn Ala Val Ala His Val
Asp Asp 75 76 Met Pro Asn Ala Leu Ser Ala
Leu Ser Asp Leu His Ala His Lys 90 91 Leu
Arg Val Asp Pro Val Asn Phe Lys Leu Leu Ser His
Cys Leu 105 106 Leu Val Thr Leu Ala Ala His
Leu Pro Ala Glu Phe Thr Pro Ala 120 121 Val
His Ala Ser Leu Asp Lys Phe Leu Ala Ser Val Ser
Thr Val 135 136 Leu Thr Ser Lys Tyr Arg
11
ﾟ???????
1 2 3 4 5 6 7 8
9 10 11 12 13 14 15 1 Val
His Leu Thr Pro Glu Glu Lys Ser Ala Val Thr Ala
Leu Trp 15 16 Gly Lys Val Asn Val Asp
Glu Val Gly Gly Glu Ala Leu Gly Arg 30 31
Leu Leu Val Val Tyr Pro Trp Thr Gln Arg Phe Phe
Glu Ser Phe 45 46 Gly Asp Leu Ser Thr Pro
Asp Ala Val Met Gly Asn Pro Lys Val 60 61
Lys Ala His Gly Lys Lys Val Leu Gly Ala Phe Ser
Asp Gly Leu 75 76 Ala His Leu Asp Asn Leu
Lys Gly Thr Phe Ala Thr Leu Ser Glu 90 91
Leu His Cys Asp Lys Leu His Val Asp Pro Glu Asn
Phe Arg Leu 105 106 Leu Gly Asn Val Leu Val Cys
Val Leu Ala His His Phe Gly Lys 120 121 Glu
Phe Thr Pro Pro Val Gln Ala Ala Tyr Gln Lys
Val Val Ala 135 136 Gly Val Ala Asn Ala Leu
Ala His Lys Tyr His
12
ﾟ?????????
ﾟ?????58??74????????a????????
Pro Lys Val Lys Ala His Gly Lys Lys Val Leu Gly
Ala Phe Ser Asp Gly
13
ﾟ?????????
14
ﾟ?????????
15
??????
???????a????2??ﾟ????2???????(a2ﾟ2)
????????????? 4????
16
???????
??????????????????????????????????????????????????
?????????????????????(5000???????)?
??????????????????????
17
????????
??????????????????????????????????????????????????
??????????
???????????(HbS)?????????????(HbA)???????????????
18
????????
HbS?HbA???????HbS??2???4??????????????????????
19
???
??????????????????????????????????????????????????
???????????????????(molecular disease)????????????
???????????????
20
???
??????????????????????????????????????????????(??
????)???????? ???????(?????????)???????????????
?????????????????
21
????????
22
????????
???????1????????????????????????????????????18???
???????6?????????HbA????????Glu????HbS?????Val????
??????????
???????????????1??????????????????
23
HbS??????????
??????????????????????????????????????????????????
ﾟ????
24
HbS??????????
6?????????(??)????(???)??
???????????
25
HbS??????????
????????????????????????????????????????????
26
HbS??????????
?????????????????????
27
HbS??????????
????HbS???????????????????????????????????????????
???
28
HbS????
6???????????????????????????????????????
1 2 3 4 5
6 7 8ATG/GTG/CAC/CTG/ACT/CCT/GAG/GAG
/AAG/ Val - His - Leu - Thr - Pro -
Glu - Glu - Lys
ATG/GTG/CAC/CTG/ACT/CCT/GTG/GAG/AAG/
Val - His - Leu - Thr - Pro - Val - Glu - Lys
???????????????????????
29
HbS????
??????????????????
?????????????????????
??????????
30
?????????
??????????????
P?
??????(?????)
Q?
?????????
31
HbS????
a?????16p13.3(?16????P??13???3)?ﾟ????????11p15.5(?
11????P??15???5)??????
????????????????2??4??????????????????????????????
???????????????????
32
HbS????
????????????????????11??????????ﾟ?????????????????
?????????????????????
?????????????????????(??)?????????????????????????
?????
33
????
?????????????????????????
???DNA????????????????????
34
???????
????????????DNA???(ATCG)??????????????????????????
?????
???????????????????????
35
DNA?????
36
???????
1)?????????????(??)
2)?????????????
3)??????????????
37
?????????????
DNA???ATGC?1???????????????????
1)???????????????? ??????(silent mutation)
2)???????????????? ????????????? (synonymous
mutation)
38
3)???????????????? ???????????????? (missense
mutation)
4)???????????????? (nonsense mutation)
39
???????ｷ?????
DNA?????????????????????????????
????????????????????????????????????(frameshift
mutation)
40
???????
??????????????3???????????????????????????????????
???(???????ｷ??)????????
41
??????
?????? ????????????? ???????????????? ??????????
?????? ???????????????? (???)
42
?????????????
??? ??? ??? ?????? ??? ??? ??? ??? ??? ??? ???
??? ??? ??? ?????? ??? ??? ??? ??? ??? ??? ???
43
?????????????
??? ??? ??? ?????? ??? ??? ??? ??? ??? ??? ???
??? ??? ??? ??????
44
????????????
? ? ??? ??? ?????? ??? ??? ??? ??? ??? ??? ???
??? ??? ??? ?????? ??? ??? ??? ??? ??? ??? ???
45
????????????
???? ??? ??? ?????? ??? ??? ??? ??? ??? ??? ???
??? ??? ??? ?????? ??? ??? ??? ??? ??? ??? ???
46
???????
??????????????????????
??
??
??????????????????????????????????
47
???????
????????????????????????
?
??
??
???????????????????????????????????????????
48
?????
?????????????????????(???????)????????????????????
????
???????????????????????????
49
?????
??????ｷ?????????????(1785???????????93.3 x 4.8
cm?????????ｷ?????)???????? Lips and Jaw???????????
50
?????
???????????????????????????Jacques-Louis
David???????????(1793)??????????????
51
Jacques-Louis David????????????
52
??????????
??????????????????????????????????????????????????
????
??????????????????????????????????????????????????
??????
53
???????
??????????????????????????????DNA???(ATCG)????????
????????????????????????????????????????????????
??????????????????
54
?????????
????????
????????????????????????
??????????????????????????????
55
?????????
??????????????????????????????????????????????????
????(?????)?????????????????????????????
?????????(??????)????????????????
56
?????????
???? (???????????)
???? (??????????????)
?????
?????
?????
?????
????
????
57
?????????
???? (??????????)
???? (???)
DNA
DNA??
????
????
????
????
58
???????
???DNA?????????????????????????????????????????? (
?????)?
?????????????????????????
59
?????
?????????????????????????????????
?????DNA??????
60
????????
???????????????????????????
??????????(?????)???????????????????????????
61
??????????
?????????????????????????????????
??????????(somatic mutation)????????????(germline
mutation)??????
62
?????????
????????????
?????????
???????????????
?????????????
????????(?????)
????????????
63
??????
?????????????????????????????????????(??)?????????
??
64
???(dwarfism)
?????Diego Velazquez?????The Dwarf Sebastian de
Morra?????????????????????????
65
??????????????????2?????????????????????
66
???(dwarfism)
70????????(Achondroplasia)???????????????????????
????????FGFR3 (fibroblast growth factor receptor
3, ????????????)???? (4p16.3)?????????????????????
???
67
????
?????
?????????????? ????????????? (???????????)
??????
??????????????? ????? (????)
68
??(????)???
???????
69
???(dwarfism)
??????????????????????????????????????????????????
???????????????????????????????
Gly380Arg (in 806aa)
70
????????????? ??????????
71
??????????
???????(natural mutation)
DNA??????
?????????
???????(induced mutation)
??????????????????DNA???
72
??????????
???????(natural mutation)
DNA??????????????(??????????)????????????????
???????????????????????????????????????DNA????????
?????????
73
DNA???
???????????????
74
??????????
???????(induced mutation)
????????????????????????????????????????DNA???????
???? ?????
75
???????
?????? ???????????????
76
???????DNA???
?????DNA??????????????????
77
???????????
???? ? ??? (genotype) (phenotype)
DNA ? ?????
78
???????????
?????????????????
??A??C????????????????????????????????????????????
?????????????
79
???????????
????????????????????????????????????????
??
???????(????????)
80
???????????
????1???????????????????????????
???
?????
??????????(albinism)
81
???????????? ????????
82
??????
?????????????????????????????????????(??)?????????
??
83
???????????
???????????(melanocyte)???????(melanin
granule)? ???????
84
???????????
85
???????????
86
?????
????????????????????????
87
???????????
??????
?????
88
???????
????????????????????????????????????
Pheo- melanin
DOPA quinone
tyrosine
DOPA
Eumela-nin
89
??????
??????????????????????????????????????????????????
??????????????????????
90
??????????
????????????????????????????(???)?????????????????
????????????????????
91
??????
????????? ????????? ???????????????? ????????? ??
??????? ?????????? ???????????????
?????(???)?????????????????
92
???????????
?????????????????(??????????)?????????????????????
??
???????????????????????????
93
??????????
??(breakage) ?????? ??(deletion) ??(duplication)
??(inversion) ??(translocation)
94
???????
95
????????????? ??????????? ?????
96
??????????
??????(natural mutation)
??????
?????
?????????
?????
??????(induced mutation)
??????????????????
?????
97
??????????
DNA??????????????????????????????????????????????
????????????????????????DNA???????????????????????
???????????????????????
98
DNA???????????
99
??????????
DNA???????????????? ????????
DNA?????????????? DNA??????ﾟ?????? DNA???????
??
100
DNA??????ﾟ
DNA??????ﾟ??????????????????????????
101
DNA??????ﾟ??? ??????
102
????????
???????
????????
???????????????
????????
????????
103
?????????????
DNA?????????????????????DNA?????????????
DNA?????????????????????????????????????????????DN
A??????????????????