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Animal Breeding & Genomics Centre
Animal Breeding & Genomics Centre
Nutrigenomics in poultry nutritionInternational Symposium – Nutrition and gut health to manage today’s challenges in poultry production. Wageningen, The Netherlands, Wednesday, 3 June 2009
Mari Smits
Animal Breeding & Genomics Centre
Overview
IntroductionGenomicsNutrigenomicsExample 1 – 3Conclusions
Animal Breeding & Genomics Centre
Nutrition and performance traits
Variation in genome (DNA)
Variation innutrition
Variation in performance traits
Animal Breeding & Genomics Centre
CostsReturnsDeveloping improved animal feeds (knowledge based)
Breeding animals with the most profitable genes
Making the profitable genes to work harder and better
Knowledge profits
Animal Breeding & Genomics Centre
NutrigenomicsGenomics
NutritionPerformance
Nutrigenomics
Animal Breeding & Genomics Centre
DNA is the carrier of all genetic informationDNA
RNA
Protein
Metabolites
Structure
Transport
Communication
Regulation
Animal Breeding & Genomics Centre
Genomics: analysis of all genes instead of one
DNA sequence
SequencingSequencing MetabolomicsMetabolomicsMicroarraysMicroarrays
Gene activity Proteins
ProteomicsProteomics
Metabolites
Applications
BioinformaticsBioinformatics
Knowledge
Animal Breeding & Genomics Centre
DNA structure and variation
AGCTGGGCCAATAGACAGCGATAGATTGACCAAAGTRCGCGCCTTTAAAAGGCT
GCTTAGCATGTAGATTGACCAAATAGATTGACCACTGGGCCAATAGAAACTGGGC
CAATAGAAGCTGGGCCAATAGACAGCGATAGATTGACCAAAGTRCGCGCCTTTAA
AAGGCTGCTTAGCATGTAGATTGACCAAATAGATTGACCACTGGGCCAATAGAAA
TGGGCCAATAGAAGCTGGGCCAATAGACAGCGATAGATTGACCAAAGTRCGCGC
TTTAAAAGGCTGCTTAGCATGTAGATTGACCAAATAGATTGACCACTGGGCCAATA
GAAACTGGGCCAATAGAAGCTGGGCCAATAGACAGCGATAGATTGACCAAAGTRC
GCGCCTTTAAAAGGCTGCTTAGCATGTAGATTGACCAAATAGATTGACCACTGGG
CCAATAGAAACTGGGCCAATAGA
AGCTGGGCCAATAGACAGCGATAGATTGACCAAAGTRCGCGCCTTTAAAAGGCT
GCTTAGCATGTAGATTGACCAAATAGATTGACCACTGGGCCAATAGAAACTGGGC
CAATAGAAGCTGGGCCAATAGACAGCGATAGATTGACCAAAGTRCGCGCCTTTAA
AAGGCTGCTTAGCATGTAGATTGACCAAATAGATTGACCACTGGGCCAATAGAAA
TGGGCCAATAGAAGCTGGGCCAATAGACAGCGATAGATTGACCAAAGTRCGCGC
TTTAAAAGGCTGCTTAGCATGTAGATTGACCAAATAGATTGACCACTGGGCCAATA
GAAACTGGGCCAATAGAAGCTGGGCCAATAGACAGCGATAGATTGACCAAAGTRC
GCGCCTTTGAAAGGCTGCTTAGCATGTAGATTGACCAAATAGATTGACCACTGGG
CCAATAGAAACTGGGCCAATAGA
Effect on trait?
Animal Breeding & Genomics Centre
Genome sequence Gallus gallus
WASHUC2 is an assembly of the
Chicken, Red Jungle Fowl
Statistics
Assembly: WASHUC2, May 2006
Genebuild: Ensembl, Aug 2006
Database version: 48.2f
Known genes: 4,782
Projected genes: 7,432
Novel genes: 4,522
Pseudogenes: 96
RNA genes: 655
Genscan gene predictions: 40,505
Gene exons: 182,183
Gene transcripts: 22,291
SNPs: 3,202,570
Base Pairs*: 1,050,947,331
http://www.ensembl.org/Gallus_gallus/index.htmlWe know all the genes and proteins including their structures
Animal Breeding & Genomics Centre
Transcriptomics, proteomics: analysis of all mRNA, proteins, . .
DNA sequence
SequencingSequencing MetabolomicsMetabolomicsMicroarraysMicroarrays
Gene activity Proteins
ProteomicsProteomics
Metabolites
Applications
BioinformaticsBioinformatics
Knowledge
Animal Breeding & Genomics Centre
Measuring gene activity
B > A
A > B
A = B
A BDiet A Diet B
Animal Breeding & Genomics Centre
Protein profiling – snapshot of “all proteins” in sample
Animal Breeding & Genomics Centre
Functional genomics research
treatment
endpoint
functional genomic studies
Understanding biological processes leading to endpoint
Tools to measure, monitor, modulate, develop
endpoint
Animal Breeding & Genomics Centre
NutrigenomicsNutrigenomics is the study of molecular relationships between nutrition and the response of genes.
The aim of nutrigenomics is to extrapolate how nutrition-induced gene expression changes affect performance traits.
Nutrigenomics focuses on the effect of nutrients on the genome, transcriptome, proteome, and metabolome.
By determining the mechanism of the effects of nutrients or the effects of a nutritional regime, Nutrigenomics tries to define the relationship between these specific nutrients or specific nutrient regimes (diets) and performance traits.
Nutrigenomics is a new science, still in its infancy but is expanding rapidly
Animal Breeding & Genomics Centre
Nutrigenomics
Animal Breeding & Genomics Centre
Nutrigenomics studies - trends
Host Microbes
Food/Feed
Gastrointestinal
track
Imm
une awareness
and competence
Energy partioningand m
etabolism
Gastrointestinalfunctioning
Healthy populations
Healthy organism(human and animal)
Animal Breeding & Genomics Centre
Bioinformatics
Microarrays
Proteomics
Storage, management,integration, interpretation
Genomics
Genetics
Physiology
data
data
data
datadata
data
Metabolomics
Comparative genomics:
Transfer of knowledge from one species to another
Animal Breeding & Genomics Centre
Genetic Regulation of Feed Intake and Energy Balance in Poultry
A better understanding of the genes associated with controlling feed intake and energy balance and how their expression is regulated by nutritional and hormonal stimuli will offer new insights into current poultry nutrition, breeding and management practices.
Animal Breeding & Genomics Centre
Example 1
Effect of an oil byproduct from conjugated linoleic acid (CLA) purification on CLA accumulation and lipogenic gene expression in broilers
J.H. Kim et al.
J. Agric. Food Chem. 2009, 57, 2397–2404 2397
Animal Breeding & Genomics Centre
Example 1Research question
Can CLB induce CLA accumulation in muscle without inducing ligogenesis in liver
2% CLA (conjugated linoleic acid)2% CLB (CLA byproduct)2% SAF (safflower oil)2% CON (soybean oil)
456 1-day-old male broiler chicks 4 weeks experimental feeding
No alteration in performance among the test groups.CLA accumulation efficiency in the breast muscle did not differ significantly between the CLA- and CBP-fed groups
Measured in liver gene activity for:sterol regulatory element binding protein 1 (SREBP1)fatty acid synthase (FAS)acetyl coenzyme A carboxylase (ACC)malic enzyme (ME)
Animal Breeding & Genomics Centre
Example 1
SREBP1
ACC
FAS
ME
Conclusion: CBP could be an efficient dietary source that promotes CLA accumulation in broiler muscle without inducing lipogenesis in the liver
Animal Breeding & Genomics Centre
Example 2 (ASG experiment)
2 groups of 25 animals Group 1: diet AGroup 2: diet BAnalysis of gene activity in jejunum5 pools of 5 animals20K arrayEach pool tested twice
Animal Breeding & Genomics Centre
Significant up-regulated genes in diet B compared to diet A
No. Fold up (2log) Homology1 2.26 Hemoglobin-α-chain2 2.21 ch CCLi103 2.19 ENSGALT00000026140.14 2.07 chemokine ah2215 2.07 Genome Hit Contig 1336.16 1.97 NDR-2 (human) weakly similar7 1.96 Early response to neural induction8 1.92 Nuclear receptor (NroB2), weakly similar9 1.89 Insulin-induced gene 1 (Insig-1)10 1.85 Immunoglobulin Heavy Chain11 1.84 F-Box/LRR repeat protein 3A12 1.83 Cytochrome P45013 1.81 Hepatocyte growth factor like protein (HGFL)14 1.80 Thrombospondin receptor (CD#36)15 1.76 ENSGALT00000016755.1
Example 2 (ASG experiment)
Animal Breeding & Genomics Centre
Significant down-regulated genes in diet B compared to diet A
No. Fold up (2log) Homology1 3.45 Genome Hit Contig 41.1792 3.22 Squalene mono-oxygenase3 2.49 Aceteacetyl-CoA-synthase4 2.42 isopentyl-diphosphate-deltaisomerase 25 2.37 C4 methyl sterol oxidase6 2.36 B – G protein precursor/MHC 3-G antigen7 2.29 Hypothetical Protein8 2.25 Hydroxysteroid (17 beta) dehydroxygenase9 1.96 ENSGALT00000011147.110 1.84 ENSGALT00000013304.111 1.80 ENSGALT00000011832.112 1.73 ENSGALT00000022866.113 1.72 Genome Hit Contig 190.2614 1.72 α2-macroglobulin precursor α215 1.69 soluble carrier family 1
Example 2 (ASG experiment)
Animal Breeding & Genomics Centre
Example 2: conclusions, biological interpretationDiets A and B affect gene expression patterns in jejunum
Diet B downregulates cholesterol biosynthesis pathway throughInsig-1↑ (B): “inhibiting” of SREBP1CD36 ↑(B) = receptor for LDL cholesterol uptake macrophages
Some genes involved in immune functions are regulatedB-G precursor protein ↓ (B)= MHC complexchemokine ah221 ↑ (B)= T-cel chemotaxis
SREBPInsig-1
SREBP+
Animal Breeding & Genomics Centre
Example 3Maternal diet influences gene expression in intestine of offspring in chicken (Gallus gallus)
Rebel et al. 2006
Influences eggs yolk composition
Hatchability
Mortality offspring
Villus length in intestine
Susceptibility for MAS
Circulating lymphocytes
Mother diet influences intestinal development
Mother diet:
Hypothesis:
Animal Breeding & Genomics Centre
Example 3Maternal diet influences gene expression in intestine of offspring in chicken (Gallus gallus)
Week 18-30 high/low feedmix
Week 29: collection of fertilized eggs
Offspring reared under same conditions
Day 3, 14, 15 intestinal sections taken
RNA pools (5 animals per group)
Measure gene actiivity
Immunohistochemistry
Exp approach:
Animal Breeding & Genomics Centre
Example 3Maternal diet influences gene expression in intestine of offspring in chicken (Gallus gallus)
Composition of breeder feed
0.25 mg/kg0.125 mg/kgSelenium
15 mg/kg7.5 mg/kgCopper
70 mg/kg40 mg/kgZinc
16 mg/kg8 mg/kgVitamin B2
6 mg/kg3 mg/kgVitamin B1
100 mg/kgNot addedVitamin C
200 IU10 IUVitamin E
3000 IU2500 IUVitamin D
15,000 IU7500 IUVitamin A
High feed mixLow feed mix weight of broilers
0
200
400
600
800
1000
1200
1400
1600
1800
3 7 14 21 32
time in days
wei
ght i
n gr
ams
broilers of breeders lowbroilers of breeders high
Weight of broilers
Animal Breeding & Genomics Centre
Example 3Maternal diet influences gene expression in intestine of offspring in chicken (Gallus gallus)
In the intestines of the offspring, 11 genes were found to be differentially expressed at day 3 and 11 after hatch.
Genes higher expressed in the “high mix” mothers are involved in epithelial turnover and maturation.
Animal Breeding & Genomics Centre
Maternal diet influences gene expression . . . . . . . and cell proliferation patterns
In all three areas investigated, the decrease in number of proliferating cells from day 3 to day 14 is less in the offspring of the “ high mix” group.
Conclusion: mother diet influences intestinal development in offspring
Animal Breeding & Genomics Centre
Maternal diet influences gene expression . .and host respons to MAS
Experimental MAS challenge
Mother feed high and offspring regularMother feed regular and offspring regular
Offspring inoculated with MAS or Saline at day 1 of ageSampling 1,3,7,14, 21 days pi
MAS: Flattened crypt epithelium,
cystic crypt, villus atrophy
Nprmal
Time PI Lesions Low mix High mix cystic crypt + ++ Day 3 villus atrophy 0 +++ Pmn inf ++ +++++ cystic crypt +++++ +++ Day 7 villus atrophy +++ +++ Pmn inf ++++ +++ cystic crypt ++++ ++ Day 14 villus atrophy ++ +++ Pmn inf ++ +++ cystic crypt ++ 0 Day21 villus atrophy + + Pmn inf + 0
Animal Breeding & Genomics Centre
Effect of an oil byproduct from conjugated linoleic acid (CLA) purification on CLA accumulation and lipogenic gene expression in broilers.Effects of 1alpha-hydroxycholecalciferol on growth performance, parameters of tibia and plasma, meat quality, and type IIb sodium phosphate cotransporter gene expression of one- to twenty-one-day-old broilers.Short term changes in the expression of lipogenic genes in broilers (Gallus gallus).Dietary supplementation of glycine modulates inflammatory response indicators in broiler chickensEffects of source and level of magnesium on catalase activity and its gene expression in livers of broiler chickensEffects of daidzein on messenger ribonucleic acid expression of gonadotropin receptors in chicken ovarian follicles.Expression of the chicken peroxisome proliferator-activated receptor-gamma gene is influenced by aging, nutrition, and agonist administration.An examination of the role of feeding regimens in regulating metabolism during the broiler breeder grower period. 1. Hepatic lipid metabolism. Effect of early feed restriction on myofibre types and expression of growth-related genes in the gastrocnemius muscle of crossbred broiler chickensEffect of diet containing phytate and phytase on the activity and mRNA expression of carbohydrase and transporter in chickens.Effects of dehydroepiandrosterone (DHEA) on hepatic lipid metabolism parameters and lipogenic gene mRNA expression in broiler chickensDietary nitrogen intake regulates hepatic malic enzyme messenger ribonucleic acid expressionEffect of manganese supplementation and source on carcass traits, meat quality, and lipid oxidation in broilers
Examples of recent nutrigenomic studies in poultry
Animal Breeding & Genomics Centre
Conclusions
Nutrigenomics approaches become more important in animal nutrition research
Nutrigenomics approaches provide deeper insight into the relationships between nutrition and the response of genes
Nutrigenomics approaches provide deeper insight into the mechanisms how nutrition-induced gene expression changes affect performance traits
Nutrigenomics tools can be used to measure the physiological effects of specific nutrients or specific nutrient regimes
In the future, knowledge obtained by nutrigenomics approaches may be applied to specifically modulate performance traits by nutrition
In the future knowledge obtained by nutrigenomics approaches may be applied to develop new (more knowledge based) animal feeds / nutrient regimes
Animal Breeding & Genomics Centre
Animal Breeding & Genomics Centre
Thanks for your attention
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