Nature Medicine
  SNPs, "snips” are DNA sequence variations that occur
when a single nucleotide in the genome sequence is altered
  sSNPs are present in the protein coding regions
  The single nucleotide change does not alter the amino acid
sequence of the protein
~ACC~ATT~AAA~GAA~AAT~ATC~TTT~GGT~GTT~TCC~!
T
C
!
Ile!
Phe!
  sSNPs exist based on the redundancy of the genetic code
 Disease development, severity
 Development of complex genetic
traits
 Response to pathogens
 Response to drugs
ATC
(Phe codons: TTT, TTC)
(Ile codons: ATC, ATT, ATA)
Effect on protein:
ΔF508 CFTR is misfolded and degraded by ERAD
What are the effects on mRNA?
What are the effects function?
ΔF508
Wild type
1840
1720
1840
1760
1720
1880
1880
1760
1960
1680
1960
1800
1680
1800
2360
1920
1920
1640
2320
2360
2240
2000
1640
2320
2000
2240
2440
2400
2280
2440
1600
1560
2400
2280
1560
1520
2080
2560
2600
2080
2480
1480
2600
2560
1480
2040
2480
2040
2120
2200
2120
2520
2200
2640
2520
2640
1440
2160
2680
1440
2160
2720
2680
2720
2960
2880
2840
2880
2920
2920
2960
2840
2760
1400
2760
1400
3000
3000
3040
3040
2800
3080
3080
2800
3160
1360
3120
3120
3160
1360
3200
3200
1320
1280
1320
1280
1240
1240
1200
1200
3240
3240
3280
3280
1160
1160
240
240
1120
3320
1120
200
3320
200
1080
1080
280
280
1000
1000
3360
3360
1040
1040
160
160
960
920
960
920
360
320
360
120
120
320
3400
3400
880
880
760
760
400
400
840
840
800
800
4400
3440
4360
4400
4360
3440
4320
80
440
80
440
4320
40
40
720
720
680
680
4240
4240
4440
3’
5’
3’
5’
3’
4200
3480
4280
4200
4280
3480
3880
560
3840
560
640
640
3880
600
3840
600
4160
4160
480
480
3920
3520
3920
4120
3520
3800
3800
4120
520
E = -1148.49
3560
3720
520
3760
3600
4080
3960
E = -1144.94
3720
3560
3760
4080
3600
3960
3640
3640
3680
3680
4000
4000
4040
4040
Translation
Protein levels and stability
Functional consequences of I507ATT
CFTR channel stability
CFTR channel gating
•  Functionally and thermally stable
I507-ATC ΔF508 CFTR
•  Wild type CFTR-like gating
properties of I507-ATC ΔF508
CFTR