1

Mutations in the Beta Globin Gene and their Effects

Holda Anagho and Alexandra Coston

2

The Central Dogma Beta Globin

Beta Globin• Nucleotide Sequence (444 nt):

ATGGTGCATCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGCAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAA

Translation (147 aa): MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH

Beta Globin Reading Frame• 5'3' Frame 1

Y I C F Stop H N C V H Stop Q P Q T D T Met V H L T P E E K S A V T A L W G K V N V D E V G G E A L G R L V S R L Q D R F K E T N R N W A C G D R E D S W V S D R H Stop L S L P I G L F S H P Stop A A G G L P L D P E V L Stop V L W G S V H S Stop C C Y G Q P Stop G E G S W Q E S A R C L Stop Stop W P G S P G Q P Q G H L C H T E Stop A A L Stop Q A A R G S Stop E L Q G E S Met G R L Met F S F P F F S Met V K F Met S Stop E G D K Stop Q G T V Stop N G K Q T N D C I S V E V S G S F Stop F L L F A V H N N C F L L F N S C F L F F S S P Q F L L L Y L Met P Stop H C V Stop Q K E I S L R Y I K Stop L K K K L Y T V C L V H Y Y L E Y Met C A Y L H I H N L P T L F S F I F N Stop Y I I I I H I Y G L K C N V L I C V H I L T K S G Stop F C I C N F K K C F L L L I Y F F V Y L I S N T F P N L F L S G Q Stop Stop Y N V S C L F A P F Stop R I T V I I S G L R Q Stop Q Y L C I Stop I F L H I N C N Stop C K R F H I A N S S Y N P A T I L L L F Y G W D K A G L F Stop V Q A R P F C Stop S C S Y L L S S S H S S W A T C W S V C W P I T L A K N S P H Q C R L P I R K W W L V W L Met P W P T S I T K L A F L L S N F Y Stop R F L C S L S P T T K L G D I Met K G L E H L D S A Stop Stop K T F I F I

• 5'3' Frame 2T F A S D T T V F T S N L K Q T P W C I Stop L L R R S L P L L P C G A R Stop T W Met K L V V R P W A G W Y Q G Y K T G L R R P I E T G H V E T E K T L G F L I G T D S L C L L V Y F P T L R L L V V Y P W T Q R F F E S F G D L S T P D A V Met G N P K V K A H G K K V L G A F S D G L A H L D N L K G T F A T L S E L H C D K L H V D P E N F R V S L W D A Stop C F L S P S F L W L S S C H R K G I S N R V Q F R Met G N R R Met I A S V W K S Q D R F S F F Y L L F I T I V F F C L I L A F F F F L L R N F Y Y Y T Stop C L N I V Y N K R K Y L Stop D T L S N L K K N F T Q S A Stop Y I T I W N I C V L I C I F I I S L L Y F L L F L I D T Stop S L Y I F Met G Stop S V Met F Stop Y V Y T Y Stop P N Q G N F A F V I L K N A F F F Stop Y T F L F I L F L I L S L I S F F Q G N N D T Met Y H A S L H H S K E Stop Q Stop Stop F L G Stop G N S N I S A Y K Y F C I Stop I V T D V R G F I L L I A A T I Q L P F C F Y F Met V G I R L D Y S E S K L G P F A N H V H T S Y L P P T A P G Q R A G L C A G P S L W Q R I H P T S A G C L S E S G G W C G Stop C P G P Q V S L S S L S C C P I S I K G S F V P Stop V Q L L N W G I L Stop R A L S I W I L P N K K H L F S L

• 5'3' Frame 3H L L L T Q L C S L A T S N R H H G A S D S Stop G E V C R Y C P V G Q G E R G Stop S W W Stop G P G Q V G I K V T R Q V Stop G D Q Stop K L G Met W R Q R R L L G F Stop Stop A L T L S A Y W S I F P P L G C W W S T L G P R G S L S P L G I C P L L Met L L W A T L R Stop R L Met A R K C S V P L V Met A W L T W T T S R A P L P H Stop V S C T V T S C T W I L R T S G Stop V Y G T L D V F F P L L F Y G Stop V H V I G R G Stop V T G Y S L E W E T D E Stop L H Q C G S L R I V L V S F I C C S Stop Q L F S F V Stop F L L S F F F F S A I F T I I L N A L T L C I T K G N I S E I H Stop V T Stop K K T L H S L P S T L L F G I Y V C L F A Y S Stop S P Y F I F F Y F Stop L I H N H Y T Y L W V K V Stop C F N Met C T H I D Q I R V I L H L Stop F Stop K Met L S S F N I L F C L S Y F Stop Y F P Stop S L S F R A I Met I Q C I Met P L C T I L K N N S D N F W V K A I A I S L H I N I S A Y K L Stop L Met Stop E V S Y C Stop Stop Q L Q S S Y H S A F I L W L G Stop G W I I L S P S Stop A L L L I Met F I P L I F L P Q L L G N V L V C V L A H H F G K E F T P P V Q A A Y Q K V V A G V A N A L A H K Y H Stop A R F L A V Q F L L K V P L F P K S N Y Stop T G G Y Y E G P Stop A S G F C L I K N I Y F H

• 3'5' Frame 1Q Stop K Stop Met F F I R Q N P D A Q G P S Stop Y P P V Stop Stop L D L G N K G T F N R N W T A R K R A Stop Stop Y L W A R A L A T P A T T F Stop Stop A A C T G G V N S L P K Stop W A S T Q T S T L P R S C G R K I R G Met N Met I S K R A Stop L G L R I I Q P Y P N H K I K A E W Stop L D C S C Y Stop Q Y E T S Y I S Y N L Y A E I F I C R D I A I A L T Q K L S L L F F R Met V Q R G Met I H C I I I A L K E R D Stop G K Y Stop K Stop D K Q K S I L K E E S I F Stop N Y K C K I T L I W S I C V H I L K H Y T L T H K Y V Stop Stop L C I N Stop K Stop K K I K Stop G D Y E Y A N K H T Y I P N S N V L G R L C K V F F Stop V T Stop C I S E I F P F V I H N V K A L S I I V K I A E K K K K E S K N Stop T K E N N C Y E Q Q I K E T K T I L R L P H Stop C N H S S V S H S K L Y P V T Y P L P Met T Stop T Stop P Stop K R R G K K T S S V P Stop T H P E V L R I H V Q L V T V Q L T Q C G K G A L E V V Q V S Q A I T K G T E H F L A Met S L H L R V A H N S I R S G Q I P K G L K E P L G P R V D H Q Q P K G G K I D Q Stop A E R V S A Y Q K P K S L L C L H Met P S F Y W S P Stop T C L V T L I P T C P G P H H Q L H P R S P C P T G Q Stop R Q T S P Q E S D A P W C L F E V A S E H S C V R S K C

• 3'5' Frame 2N E N K C F L L G R I Q Met L K A L H N I P Q F S S W T Stop G T K E P L I E I G Q Q E S E L S D T C G P G H Stop P H Q P P L S D R Q P A L V G Stop I L C Q S D G P A H R P A R C P G A V G G R Stop E V Stop T Stop L A K G P S L D S E Stop S S L I P T I K Stop K Q N G S W I V A A I S N Met K P L T S V T I Y Met Q K Y L Y A E I L L L P Stop P R N Y H C Y S L E W C K E A Stop Y I V S L L P Stop K K E I R E S I R N K I N K K V Y Stop K K K A F F K I T N A K L P Stop F G Q Y V Y T Y Stop N I T L Stop P I N Met Y N D Y V S I K N K R K Stop S R E I Met N Met Q I S T H I F Q I V Met Y Stop A D C V K F F F K L L N V S Q R Y F L L L Y T Met L R H Stop V Stop Stop Stop K L R R R K K K K A R I K Q K K T I V Met N S K Stop K K L K R S Stop D F H T D A I I R L F P I L N C T L L L I P F L Stop H E L N H R K E G E R K H Q A S H R L T L K F S G S T C S L S Q C S S L S V A K V P L R L S R Stop A R P S L K A P S T F L P Stop A F T L G L P I T A S G V D R S P K D S K N L W V Q G Stop T T S S L R V G K Stop T N R Q R E S V P I R N P R V F S V S T C P V S I G L L K P V L Stop P Stop Y Q P A Q G L T T N F I H V H L A P Q G S N G R L L L R S Q Met H H G V C L R L L V N T V V S E A N V

• 3'5' Frame 3Met K I N V F Y Stop A E S R C S R P F I I S P S L V V G L R E Q R N L Stop Stop K L D S K K A S L V I L V G Q G I S H T S H H F L I G S L H W W G E F F A K V Met G Q H T D Q H V A Q E L W E E D K R Y E H D Stop Q K G L A W T Q N N P A L S Q P Stop N K S R Met V A G L Stop L L L A I Stop N L L H Q L Q F I C R N I Y Met Q R Y C Y C L N P E I I T V I L Stop N G A K R H D T L Y H Y C P E R K R L G K V L E I R Stop T K K Y I K R R K H F L K L Q Met Q N Y P D L V N Met C T H I K T L H F N P Stop I C I Met I Met Y Q L K I K E N K V G R L Stop I C K Stop A H I Y S K Stop Stop C T R Q T V Stop S F F L S Y L Met Y L R D I S F C Y T Q C Stop G I K Y N S K N C G E E K K R K Q E L N K R K Q L L Stop T A N K R N Stop N D P E T S T L Met Q S F V C F P F Stop T V P C Y L S P S Y D Met N L T I E K K G K E N I K R P I D S P Stop S S Q D P R A A C H S A A H S V W Q R C P Stop G C P G E P G H H Stop R H R A L S C H E P S P Stop G C P Stop Q H Q E W T D P Q R T Q R T S G S K G R P P A A Stop G W E N R P I G R E S Q C L S E T Q E S S L S P H A Q F L L V S L N L S C N L D T N L P R A S P P T S S T F T L P H R A V T A D F S S G V R C T Met V S V Stop G C Stop Stop T Q L C Q K Q Met

Beta Globin Reading Frame (Cont’d.)

• 5'3' Frame 1Met V H L T P E E K S A V T A L W G K V N V D E V G G E A L G R L L V V Y P W T Q R F F E S F G D L S T P D A V Met G N P K V K A H G K K V L G A F S D G L A H L D N L K G T F A T L S E L H C D K L H V D P E N F R L L G N V L V C V L A H H F G K E F T P P V Q A A Y Q K V V A G V A N A L A H K Y H Stop

• 5'3' Frame 2W C I Stop L L R R S L P L L P C G A R Stop T W Met K L V V R P W A G C W W S T L G P R G S L S P L G I C P L L Met L L W A T L R Stop R L Met A R K C S V P L V Met A W L T W T T S R A P L P H Stop V S C T V T S C T W I L R T S G S W A T C W S V C W P I T L A K N S P H Q C R L P I R K W W L V W L Met P W P T S I T

• 5'3' Frame 3G A S D S Stop G E V C R Y C P V G Q G E R G Stop S W W Stop G P G Q A A G G L P L D P E V L Stop V L W G S V H S Stop C C Y G Q P Stop G E G S W Q E S A R C L Stop Stop W P G S P G Q P Q G H L C H T E Stop A A L Stop Q A A R G S Stop E L Q A P G Q R A G L C A G P S L W Q R I H P T S A G C L S E S G G W C G Stop C P G P Q V S L

• 3'5' Frame 1L V I L V G Q G I S H T S H H F L I G S L H W W G E F F A K V Met G Q H T D Q H V A Q E P E V L R I H V Q L V T V Q L T Q C G K G A L E V V Q V S Q A I T K G T E H F L A Met S L H L R V A H N S I R S G Q I P K G L K E P L G P R V D H Q Q P A Q G L T T N F I H V H L A P Q G S N G R L L L R S Q Met H H

• 3'5' Frame 2Stop Stop Y L W A R A L A T P A T T F Stop Stop A A C T G G V N S L P K Stop W A S T Q T S T L P R S L K F S G S T C S L S Q C S S L S V A K V P L R L S R Stop A R P S L K A P S T F L P Stop A F T L G L P I T A S G V D R S P K D S K N L W V Q G Stop T T S S L P R A S P P T S S T F T L P H R A V T A D F S S G V R C T

• 3'5' Frame 3S D T C G P G H Stop P H Q P P L S D R Q P A L V G Stop I L C Q S D G P A H R P A R C P G A Stop S S Q D P R A A C H S A A H S V W Q R C P Stop G C P G E P G H H Stop R H R A L S C H E P S P Stop G C P Stop Q H Q E W T D P Q R T Q R T S G S K G R P P A A C P G P H H Q L H P R S P C P T G Q Stop R Q T S P Q E S D A P

6

Beta Globin Mutations

• Hb Hammersmith• Hb Redondo• Hb Galicia• Hb Showa-Yakushiji • Hb Vercelli

6

Hammersmith

7

Hb Hammersmith

Codon 43

9

Hb Hammersmith

Phenylalanine Serine

10

Hammersmith• Wild Type

ATGGTGCATCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGCAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAA

• Mutation ATGGTGCATCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGCAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTCTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAA

11

• Wild Type Met V H L T P E E K S A V T A L W G K V N V D E V G G E A L G R L L V V Y P W T Q R F F E S F G D L S T P D A V Met G N P K V K A H G K K V L G A F S D G L A H L D N L K G T F A T L S E L H C D K L H V D P E N F R L L G N V L V C V L A H H F G K E F T P P V Q A A Y Q K V V A G V A N A L A H K Y H Stop

• Mutation Met V H L T P E E K S A V T A L W G K V N V D E V G G E A L G R L L V V Y P

W T Q R F S E S F G D L S T P D A V Met G N P K V K A H G K K V L G A F S D G L A H L D N L K G T F A T L S E L H C D K L H V D P E N F R L L G N V L V C V L A H H F G K E F T P P V Q A A Y Q K V V A G V A N A L A H K Y H Stop

Hb Hammersmith

12

More Hammersmith!

14

Redondo

15

Redondo!

Codon 92

17

Redondo

AsparagineHistidine

18

Redondo• ATGGTGCATCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAG

TTGGTGGTGAGGCCCTGGGCAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAA

• ATGGTGCATCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGCAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGAACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAA

WT

19

Redondo Protein Expression• Met V H L T P E E K S A V T A L W G K V N V D E V G G E A L G R L L V V Y P W T Q R F F E S F G D L S T P

D A V Met G N P K V K A H G K K V L G A F S D G L A H L D N L K G T F A T L S E L H C D K L H V D P E N F R L L G N V L V C V L A H H F G K E F T P P V Q A A Y Q K V V A G V A N A L A H K Y H Stop

• Met V H L T P E E K S A V T A L W G K V N V D E V G G E A L G R L L V V Y P W T Q R F F E S F G D L S T P D A V Met G N P K V K A H G K K V L G A F S D G L A H L D N L K G T F A T L S E L N C D K L H V D P E N F R L L G N V L V C V L A H H F G K E F T P P V Q A A Y Q K V V A G V A N A L A H K Y H Stop

WT

20

Redondo

22

Galicia

23

GALICIA!

- Codons 97 and 98

25

Hb Galicia

Histidine

ANDValine

DELETED!!!

27

Hb Galicia

ADDED!!!Leucine

26

Galicia• ATGGTGCATCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAG

TTGGTGGTGAGGCCCTGGGCAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAA

• ATGGTGCATCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGCAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGC TGGATCCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAA

WT

27

Galicia Protein Expression

• Met V H L T P E E K S A V T A L W G K V N V D E V G G E A L G R L L V V Y P W T Q R F F E S F G D L S T P D A V Met G N P K V K A H G K K V L G A F S D G L A H L D N L K G T F A T L S E L H C D K L H V D P E N F R L L G N V L V C V L A H H F G K E F T P P V Q A A Y Q K V V A G V A N A L A H K Y H Stop

• Met V H L T P E E K S A V T A L W G K V N V D E V G G E A L G R L L V V Y P W T Q R F F E S F G D L S T P

D A V Met G N P K V K A H G K K V L G A F S D G L A H L D N L K G T F A T L S E L H C D K L L D P E N F R L L G N V L V C V L A H H F G K E F T P P V Q A A Y Q K V V A G V A N A L A H K Y H Stop

WT

28

Galicia

30

Hb Showa-Yakushiji

32

Hb Showa-Yakushiji

Codon 110

Hb Showa-Yakushiji

33

Leucine Proline

Wild Type Hb• Nucleotide Sequence (444 nt): 

ATGGTGCATCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGCAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAA

Translation (147 aa): MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLG

AFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH

Hb Showa-Yakushiji

• Nucleotide Sequence (444 nt): ATGGTGCATCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGCAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGCTCCTGGGCAACGTGCCGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAA

• Translation (147 aa): MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLG

AFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVPVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH

Hb Showa-Yakushiji

38

Hb Vercelli

40

Hb Vercelli

Codon 126

41

Hb Vercelli

DELETED!!!

Wild Type Hb• Nucleotide Sequence (444 nt): 

ATGGTGCATCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGCAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAGTGCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAA

Translation (147 aa): MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLG

AFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH

Hb Vercelli• ATGGTGCATCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCTGTGGGGCAAGGTGAACGTGGATGAAG

TTGGTGGTGAGGCCCTGGGCAGGCTGCTGGTGGTCTACCCTTGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATGCTGTTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGTGCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTGCCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAACTTCAGGCTCCTGGGCAACGTGCTGGTCTGTGTGCTGGCCCATCACTTTGGCAAAGAATTCACCCCACCAG GCAGGCTGCCTATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCACTAA

Translation (147 aa): MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLG

AFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPGRLPIRKWWLVWMPWPTSITKLAPLLSNP(156)Y-COOH

Hb Vercelli