Nlm presentation qtl for fat

Animal Breeding & Genomics Centre

Whole Genome Scan:QTL for Milk Fat Composition in

Summer

Nazir A Ganai

Tuesday 24th March 2009


Milk Genomics Initiative

Aim: Identify opportunities to use genetic variation to improve milk quality characteristics

Milk quality: Milk-Protein composition Milk-fat composition

Improve: Technological efficiency (production of cheese, butter) Innovative dairy products (e.g. promoting human health)


Milk Fat composition

ImportanceMajor energy component - 2.25 times caloric value of CHOs

Farmers: for economics

Industry: for quality dairy products

Designer Milk: for good healthAn (indirect) aim of the Milk Genomics Initiative

MGI aims to find the QTL / genes underlying the variation of milk fat composition

Ultimately propose genetic interventions to alter the milk fat composition for good health and/or better processing qualities


Human versus Cow milk composition

Constituent Human milk

Cow milk

Protein % protein 1.3 % 3.5%

Casein : Whey protein 40:60 80:20

Fat % fat 3.9% 4.0%

Saturated 1.8 g/100g 2.5

Mono-Unsaturated 1.6 1.0

Poly-unsaturated 0.5 0.18


Milk Fat Composition Normal Milk

Fat % 3 to 5% SFA ~68% MUFA ~27% PUFA ~5%

Ideal milk

Fat % ~2% SFA < 8% MUFA 82% PUFA 10%


Milk Fatty acids and human health

Type of Fat Role Effect

Sat. Fatty Acids Lauric acid (12:0)Palmitic acid 16:0Myristic acid

Raise LDL Cholestrol

•Atheroseclerosis•High BP•CHD

Trans fatty acids Trans 18:1

Unsat. Fatty acids

Oleic acid cis 18:1Linoleic acid 18:2Linolenic acid 18:3

Lower LDL Cholestrol Good for health


Milk Fat Profi le• 400 different FA in milk

• Different ways to classify

•Origin in Milk

•Short / Medium Chain: synthesized de novo

•Long Chain : preformed-

•Melting point:

•Saturated

•Un saturated

•Biological properties

•Good for health

•Bad


SFA ~68%

MUFA~27%

PUFA ~5%

C4:0 to C20:0C14:0 = ~12%

C16:0 = ~30% Palmitic acid

C18:0 = ~10%

C10:1 to C18:1C18:1cis9 = ~21%

C18:1trans = ~2.15% C16:1 = ~1.4%

C14:1 = ~1.16%

C18:2 cis9,12 (Linoleic acid) 1.12

CLA cis9, trans11(C18:2) Rumenic acid 0.56

C18:3 cis9,12,15 α-Linolenic acid 0.50

Fatty Acid Profile


Variability in milk fat composition Environmental:

FA profile highly sensitive to the kind of feed Summer milk fat – low in saturated, high in unsaturated

Trait Summer Winter

UFA 29.24 25.5

C18trans 2.14 1.50

CLAcis 9, tr 11 0.56 0.39

C18:3 cis9,12,15 0.50 0.41

C16:0 29.0 32.6


Heritability Short and medium chain 0.23 to 0.57 Long chain FA 0.12 to 0.33

Genes involved in biosynthesis of milk : > 40 To find genes causing genetic variation :

difficult Therefore, the first approach to is find QTL

underlying the genetic variation


Aim

To find QTL for milk fat composition in summer

Compare the results with winter milk fat analysis


Material & Methods

• Resource population

• 1905 Cows

• 398 herds

• 7-sire families

• Milk sampling

• Summer

• Marker Map: 1341 SNPs over 29 autosomes

• Analysis: Multi-marker regression analysis


Genome Scan Results

Total fat Traits: 46 Significant QTL (PGenome <0.05) : 4

BTA14, BTA15, BTA26, BTA27 Variation explained in: 33 traits

Suggestive QTL: 20 Variation explained in: 44 traits


Resource population

873 cows

50 bulls

5 bulls

848 cows


Material & Methods Milk sample

Capillary zone electrophoresis

Blood sample DNA analyses

• 1912

• 398

• Pedigree

• 1

• Winter

• 1

Minutes

-6 -4 -2 0 2 4 6 8 10 12 14 16 18 20 22

AU

0.00

0.01

0.02

0.03

0.04

0.05

0.06

0.07

0.08

0.09

AU

0.00

0.01

0.02

0.03

0.04

0.05

0.06

0.07

0.08

0.09

BS

A 5

614

1B

SA 1

14

80 2

3

42

4 3

a-la

c 9

430

1 4

b-L

g-B 2

13

051 5

b-L

g-A

1

50

588 6

1

80

00 7

6

57

7 8

7

75

5 9

1

16

39 1

0

1

37

34

11

2

89

72 1

2

4

38

67 1

3

a-C

as-S

2 1

43

20

9 1

4

61

673

15

1

22

40

3 16

1

716

21 1

7

2

22

88

0 18

a-C

as-S

1 12

97

19

8 19

3

36

30 2

0 3

98

04 2

1

a-C

as-S

0 5

301

53 2

2

3

43

83 2

3 3

82

13 2

4

k-C

as 2

58

19

1 2

5 5

74

32 2

6

b-C

as-B 5

11

23 2

7

1

01

99

5 28

b-C

as-A

1 1

092

82

7 2

9

8

65

9 3

0

b-C

as-A

2 1

07

15

99 3

1 1

30

83

8 3

2

7

47

6 3

3 1

15

43 3

4 1

17

67 3

5

2

39

53 3

6 3

38

24 3

7

3

11

27 3

8 1

29

75 3

9

2

12

4 4

0

3

17

03 4

1

9

50

7 4

2

21

343

43

2

924

8 4

4

27

57

7 4

5

PDA - 214nm11891

NameAreaPk #


Detection of DNA regions Using 1341 Single Nucleotide Polymorphisms

(SNPs) as genetic markers

Ind 1 CACCGCGCCT GGTCCC G TTT TGGCTATTCT

CACCGCGCCT GGTCCC G TTT TGGCTATTCT

Ind 2 CACCGCGCCT GGTCCC A TTT TGGCTATTCT

CACCGCGCCT GGTCCC A TTT TGGCTATTCT

Genetic markers can be used to reconstruct the inheritance from parents to offspring



BTA-14: Long Chain Fatty Acids

0

5

10

15

20

1 5 9 13 17 21 25 29 33 37 41 45 49 53 57 61 65 69 73 77 81 85 89 93 97 101cM

F v

alu

e

0

0.25

0.5

0.75

1

Info

rma

tion

Co

nte

nt

C18:1

C18:1 cis9

C18:2

C18:2 cis9,12

c183

fat%

ratio SFA/UFA

SFA

Total index

UFA

IC

BTA-14: Medium & Shrot Chain FA

0

2

4

6

8

10

12

14

16

18

1 6 11 16 21 26 31 36 41 46 51 56 61 66 71 76 81 86 91 96 101

cM

F v

alu

e

0

0.25

0.5

0.75

1

Info

rmat

ion

Co

nte

nt

C7:0

C9:0

C11:0

C13:0

C16:0

C16:1

IC


BTA 26: QTL at 28 cM for Mono-unsaturated Fatty Acids

0

5

10

15

1 11 21 31 41 51 61

F v

alu

e

0

0.25

0.5

0.75

1

Info

rmat

ion

Co

nte

nt

C10:1

C14:1

C16:1

C10index

C12index

C14index

C16index

IC


Variance explained by DNA regions

Chromosome Trait VQTL (%)

14 Fat% 12

SFA 9.2

UFA 8.7

FA 3 - 10%

2627

MUFAC5:0, C11:0

1 – 4%1.3 – 1.8%


Comparison between results on summer & winter samples

#BTA Position Summer Fat Winter Fat

6 - - C6:0, C8:0

14 0 cM 24 traits 21 traits : sameExceptions: C6:0, C8:0, C10:0

15 38 cM9 cM

C4:0C17:0

C18:1 trans

16 - - C18indexCLAindex

19 - - C14:0

26 28 cM MUFA MUFA

27 6 cM Odd Chain FAC5 : C13

-


Comparison for individual FA

Trait rA

Chromosomes with QTL

Winter Summer

fat% 0.97 6,8,11,13,14,27 5,7,8,13,14

C4:0 0.95 2,7,19,25,27 15,18

C6:0 0.94 2,6,13,23 13,14,15

C8:0 0.94 6,14,17,29 13,14

C14:0 0.93 14,19,22,26 15,21,29

C16:0 0.78 1,4,6,9,11,14 5,14,19,24

C18:0 0.84 1,11,16,19 8,11,21,23

C18:1 cis 9 14,21 14,24,28

C16:1 1,6,13,14,19,26, 14,15,18,26,

C14:1 26,13,19 8,11,15,26

C18:2 cis 9,12 0.96 7,11,12,14 14

CLA cis9, trans 11 0.82 11,14,17 14,29

C18:3 cis9,12,15 0.83 3,14,22 9,11,14,21


Conclusion (for summer milk fat)

Detected 4 QTL on BTA14, 15, 26 and 27 for summer milk fat composition.

QTL on BTA14 significantly influenced most of the traits, both saturated and unsaturated.

QTL on BTA15 influenced the saturated FA only (C4:0 and C17:0).

QTL on BTA26 specifical ly influenced MUFA. The source of such FA in milk is the desaturation activity of enzyme SCD, for which the gene has been already mapped to BTA26.

QTL on BTA27 specifical ly influenced odd-chain Saturated FA. The origin of such FA is different from even-chain FA.


Summer vs Winter milk fat composition

Similarit ies: Only two QTL on BTA14 and BTA26 influence the same traits in both

seasons. Dif ferences:

3 QTL on BTA6, 16, 29 influenced fat composition in winter milk only. QTL on BTA27 is influenced fat composition in Summer milk only. All the suggestive QTL on 23 other autosomes influenced different traits

in two seasons. This lack of consistency :

background ef fects like : epistasis and environmental interactions,

less powerful experimental design (half-sib structure) for QTL analysis.


Opportunities for genetic selection

Health Promoting (low fat %)I beleive there is a

long way before we can modulate the milk fat composition for a Designer Milk through marker assisted selection !!


Thank You for your attention!

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Nlm presentation qtl for fat