nlm presentation qtl for fat
TRANSCRIPT
Animal Breeding & Genomics Centre
Whole Genome Scan:QTL for Milk Fat Composition in
Summer
Nazir A Ganai
Tuesday 24th March 2009
Animal Breeding & Genomics Centre
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)
Animal Breeding & Genomics Centre
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
Animal Breeding & Genomics Centre
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
Animal Breeding & Genomics Centre
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%
Animal Breeding & Genomics Centre
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
Animal Breeding & Genomics Centre
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
Animal Breeding & Genomics Centre
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
Animal Breeding & Genomics Centre
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
Animal Breeding & Genomics Centre
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
Animal Breeding & Genomics Centre
Aim
To find QTL for milk fat composition in summer
Compare the results with winter milk fat analysis
Animal Breeding & Genomics Centre
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
Animal Breeding & Genomics Centre
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
Animal Breeding & Genomics Centre
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 #
Animal Breeding & Genomics Centre
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
Animal Breeding & Genomics Centre
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
Animal Breeding & Genomics Centre
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
Animal Breeding & Genomics Centre
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%
Animal Breeding & Genomics Centre
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
-
Animal Breeding & Genomics Centre
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
Animal Breeding & Genomics Centre
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.
Animal Breeding & Genomics Centre
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.
Animal Breeding & Genomics Centre
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 !!