Figure 1

BRAF gene mutations

Figure 2

Nucleotide frequencies of the sequences

Figure 3 Mismatch curves distribution of controls (a), benign tumors (b) and malignant tumors (c) The SSD, control (0.01093; p=0.55000), TB (0.00346; p=0.59000) and TM (0.00988; p=0.48000) values are positive and not significant for the three groups (Table 6). The values of Rag, controls (0.05005; p = 0.78000), TB (0.02122; p = 0.83000) and TM (0.03150; p=0.36000) are positive and not significant (Table VII).

NUCLEOTIDE POSITION

AMINO ACIDS

NUMBER

CONTROLS

172023A>AT

 

2

BENIGN TUMORS

171893T>TA ; mut het T1763A

L588H

1

171918T> TA ; mut het T1788A

G596G

1

171911A>AT ; mut het A1781T

D594V dbSNP 121913338

1

171912T>TC ; mut het T1782C

D594V

1

172023A>AT

 

3

172032C>CA

 

1

MALIGNANT TUMORS

171924T>TA ; mut het T1794A

A598AA

1

172021A>AT

 

4

172020T>TA

 

1

172023A>AT

 

1

172032C>CA

 

1

172032C>CT

 

1

Table 1:Nature and frequency of mutations

Diversity indices

Controls

Benign tumors

Malignant tumors

Number of sequences, n

12

31

35

Number of sites, N

181

181

181

Monomorphic sites

173

164

161

Polymorphic sites

8

17

20

Singleton variable sites

6

10

9

Parsimony informative sites

2

7

11

Total number of mutations,Eta

10

22

26

Total number of singleton

mutations Eta (s)

8

17

20

Number of haplotypes, h

6

18

23

Average             number            of

nucleotide differences (k)

2.045

3.009

3.615

Transitions (%)

26.51

21.18

46.82

Transversions (%)

73.42

78.82

53.16

R (transition rates/

transversal rates)

0.318

0.238

0.807

Haplotypical diversity (hd)

0.818

0.920

0.934

Nucleotide diversity (π)

0.01130

0.01662

0.01997

Table 2:Values of genetic diversity indices for each population

Amino acids

Controls

Benign

tumours

Malignant

tumours

P-value

T vsTB

P-value

T vs TM

P-value

TB vs TM

Ala

5.15

5.07

5.15

0.9795

1

0.9795

Cys

0.14

0.05

0.05

0.8363

0.8363

1

Asp

5.01

5.02

5.00

0.9974

0.9974

0.9948

Glu

5.01

5.02

5.00

0.9974

0.9974

0.9948

Phe

9.74

9.49

9.68

0.9522

0.9886

0.9636

Gly

6.68

6.69

6.67

0.9977

0.9977

0.9955

His

3.34

3.34

3.34

1

1

1

Ile

10.15

10.30

10.15

0.9721

1

0.9721

Lys

5.01

4.96

4.81

0.987

0.9478

0.9608

Leu

11.82

12.03

11.96

0.9635

0.9756

0.9878

Met

1.67

1.73

1.76

0.9738

0.9609

0.9871

Asn

0.00

0.05

0.10

0.823

0.7518

0.8972

Pro

1.67

1.94

2.05

0.886

0.8424

0.9556

Gln

3.34

3.34

3.34

1

1

1

Arg

3.34

3.40

3.34

0.9812

1

0.9812

Ser

10.15

10.30

10.30

0.9721

0.9721

1

Thr

6.68

6.47

6.34

0.9522

0.9224

0.9701

Val

5.01

5.02

5.00

0.9974

0.9974

0.9948

Trp

3.34

3.34

3.34

1

1

1

Tyr

2.78

2.43

3.34

0.8765

0.8182

0.7007

Table 3:Frequencies of BRAF amino acids

Groupes

Intra group genetic

distances

Inter group genetic

distances

Fst

Controls

0.01

 

0.0139

0

P-value=0.86486

Benign tumors

0.02

Controls

 

 

0.0159

0

P-value=0.76577

Malignant tumors

0.02

Benign tumors

 

 

0.0186

0

P-value=0.48649

Malignant tumors

 

Table 4:Intra- and inter-group genetic distances and differentiation index (Fst)

Parameters

Controls

Benign tumors

Malignant tumors

P-value Controls

P-value TB

P-value TM

dN/dS

0.01

0.037

0.064

1.023

1.802

1.529

D de Tajima

-0.90996

-0.99594

-0.86541

0.2

0.154

0.211

D* de Fu et

Li

-0.06286

-0.07713

-0.11543

0.46000

1.13637

0.48800

F* de Fu et Li

-0.07359

-0.05006

-0.06326

0.47100

0.45200

0.45500

H de Fay et

Wu

-0.14000

-0.06436

-0.22133

0.35400

0.33500

0.33300

R2

0.16074

0.16370

0.16088

0.000

0.000

0.000

Table 5:Values of the Selection Signature Tests

Parameters

Controls

Benign tumors

Malignant tumors

SSD

0.01093

P-value= 0.55000

0.00346

P-value= 0.59000

0.00988

P-value= 0.48000

Rag

0.05005

P-value= 0.78000

0.02122

P-value= 0.83000

0.03150

P-value=0.36000

Table 6:Values of SSDs, Rags, and their P-values