HEMOGLOBIN, 11(1), 6 1 - 6 2 ( 1 9 8 7 )

BRIEF REPORT

HEMOGLOBIN SWAN RIVER [a6(A4)ASP+GLY]

Hemoglobin Swan R i v e r (1) was de tec ted i n a 24-year-o ld female Caucasian. The v a r i a n t appeared as a band w i t h a m o b i l i t y between Hbs F and S on c e l l u l o s e a c e t a t e e l e c t r o p h o r e s i s (pH 8.6). A v a r i - a n t Hb A2 band c a t h o d i c t o normal Hb Ap was a l s o observed, i n d i - c a t i n g t h e presence o f an a c h a i n v a r i a n t . C i t r a t e agar e lec t ropho- r e s i s a t pH 6.0 revea led a band between Hbs A and S , and g l o b i n cha in a n a l y s i s i n a c i d and a l k a l i n e b u f f e r s showed an abnormal c h a i n m i g r a t i n g between t h e aA and aG P h i l a d e l p h i a chains (2 ) . The i s o - propanol t e s t ( 3 ) f o r uns tab le hemoglobins was p o s i t i v e as was t h e BCB t e s t ( 4 ) f o r i n c l u s i o n bodies. Q u a n t i t a t i o n o f a hemolysate on Mono Q a n i o n i c r e s i n (Pharmacia) r e s u l t e d i n 88.2% Hb A, 9.8% Hb Swan R ive r , and 2.0% Hb A2 (5 ) . The percentage o f Hb F was 0.5%. We were unable t o o b t a i n any hemato log ic da ta on t h i s p a t i e n t o r on h e r two c h i l d r e n who a l s o have t h e v a r i a n t .

The v a r i a n t hemoglobin was p a r t i a l l y r e s o l v e d by chromatography on DEAE-Sephadex ( 6 ) as a shoulder peak e l u t i n g ahead o f Hb A. Separat ions o f t h i s f r a c t i o n on CM-cel lu lose ( 7 ) gave a ma jo r peak o f s lower e l u t i n g v a r i a n t a c h a i n c l e a r l y r e s o l v e d f rom a m ino r peak c o n t a i n i n g t h e cJ\ chain. The v a r i a n t c h a i n was aminoe thy la ted (8) , d iges ted w i t h t r y p s i n (9), and f i n g e r p r i n t e d (10) . The p e p t i d e map i n d i c a t e d a change i n t h e p o s i t i o n o f Tp-1. T h i s p e p t i d e t h a t n o r m a l l y i s s i t u a t e d above Tp-9 was now l o c a t e d between Tp-6 and Tp-3 (11). These r e s u l t s r e v e a l e d t h a t abnormal Tp-1 was more hydrophobic and l e s s a c i d i c than t h e normal p e p t i d e was exc i sed f rom t h e map, e l u t e d and hydro lyzed. The amino a c i d compos i t i on o f t h i s pep t ide : Asp 0.0(1), Ser l . O ( l ) , Pro 0.93(1), Gly 1.0(0), A l a 0.97(1), Val l.l(l), Leu 0.7(1) and Lys 1.3(1) t h a t shows t h e s u b s t i t u t i o n o f a r e s i d u e o f g l y c i n e f o r a s p a r t i c a c i d would account f o r i t s a l t e r e d m o b i l i t y . The s u b s t i t u t i o n o f g l y c i n e f o r t h e s i n g l e r e s i d u e o f a s p a r t i c a c i d a t p o s i t i o n 6 i n Tp-1 was con f i rmed b y sequence a n a l y s i s o f t h e whole c h a i n on a Beckman 890C sequencer.

F i v e o t h e r v a r i a n t s have been desc r ibed a t t h i s p o s i t i o n : Hb Sawara (Asp-Ala) (12) , Hb Dun ( A s p A s n ) (13), Hb Ferndown ( A s p V a l ) (14) , Hb Woodvi l le (Asp+Tyr) (151, and Hb Boyle H e i g h t s (Asp-4) ( 6 ) . A l l show inc reased oxygen a f f i n i t y t h a t has been a t t r i b u t e d t o t h e l o s s o f t h e c a r b o x y l a t e which forms hydrogen bonds

Received : Mahch 3, 1986; Accepted : O&ube,t 24 , 1986 .

61

Copyright @ 1987 by Marcel Dekker, Inc.

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62 MOO-PENN ET AL.

with the OH of Ser 3(Al)a and Ser 124(H7)a. Loss of these bonds may loosen the structure as a whole (17). The cooperativity and Bohr effect were unchanged for those variants where these properties were reported.

We wish to thank S. Holland and H. Brown for technical assist- ance.

Division of Host Factors Center for Infectious Diseases Centers for Disease Control Atlanta, GA 30333

Chemical Sciences Division Texas Department o f Health Austin, TX 78756

W. F. Moo-Penn D.L. Jue

M.H. Johnson

B. L. Therrell

1. 2. 3. 4.

5. 6. 7.

8.

9. 10. 11.

12.

13.

14.

15.

16.

17.

REFERENCES

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