1. Biodiversità animale e sistemi zootecnici
Alessio Valentini
13/04/2010
Accademia Nazionale delle Scienze detta dei XL

2. Accademia Nazionale delle Scienze detta dei XL
Comparisons of domesticated wild species (left of each pair) and their never-domesticated close relatives (right) reveal the subtle factors that can derail domestication. J. Diamond, Nature 2002
13/04/2010
Accademia Nazionale delle Scienze detta dei XL

3. Rules for animal domestication
a diet not easily supplied by humans (hence no domestic anteaters),
slow growth rate and long birth spacing (for example, elephants and gorillas),
nasty disposition (grizzly bears and rhinoceroses),
reluctance to breed in captivity (pandas and cheetahs),
lack of follow-the-leader dominance hierarchies (bighorn sheep and antelope),
and tendency to panic in enclosures or when faced with predators (gazelles and deer, except reindeer)
13/04/2010
Accademia Nazionale delle Scienze detta dei XL

4. Accademia Nazionale delle Scienze detta dei XL
13/04/2010
Accademia Nazionale delle Scienze detta dei XL

6. The mystery of Etruscan origins: novel clues from Bos taurus mitochondrial DNA
Marco Pellecchia,1 Riccardo Negrini,1 Licia Colli,1 Massimiliano Patrini,1 Elisabetta Milanesi,1† Alessandro Achilli,2 Giorgio Bertorelle,3 Luigi L Cavalli-Sforza,4 Alberto Piazza,5 Antonio Torroni,2 and Paolo Ajmone-Marsan1*
Proc Biol Sci May 7; 274(1614): 1175–1179.

7. B. Chessa et al., Science 324, 532 -536 (2009)
Fig. 2 Combination of enJSRV proviruses (retrotypes) in the domestic sheep
B. Chessa et al., Science 324, (2009)
Published by AAAS

8. B. Chessa et al., Science 324, 532 -536 (2009)
Fig. 3 Genetic distances between sheep populations on the basis of enJSRVs insertion frequencies
B. Chessa et al., Science 324, (2009)
Published by AAAS

9. Accademia Nazionale delle Scienze detta dei XL
Lactose intolerance by region (African countries are only a rough guess). Red indicates a high percentage of intolerance, green a low percentage. Wikipedia.org
13/04/2010
Accademia Nazionale delle Scienze detta dei XL

10. Accademia Nazionale delle Scienze detta dei XL
Approximate posterior density of region of origin for LP/dairying co-evolution.
Itan Y, Powell A, Beaumont MA, Burger J, Thomas MG, 2009 The Origins of Lactase Persistence in Europe. PLoS Comput Biol 5(8)
13/04/2010
Accademia Nazionale delle Scienze detta dei XL

11. Central Dogma of Genetics

12. Breeds of cattle
Why so many colors?

13. Molecular causes of Mc1r loss-of-function
DG104
red cow
(Klungland, 1995)
DC183
yellow mouse
(Robbins, 1993)
R306ter
Irish Setter
(Newton, 2000)
C33T
red chicken
(Takeuchi, 1996)
S83F
chestnut horse
(Marklunk, 1996)
A240T
red pig
(Kijas, 1998)
R151C
red hair
(Rees, 1997)

14. And the dominant black phenotype in several species is due to activating mutations in the melanocortin 1 receptor.Activation of the Mc1r results in an increase in cAMP and eumelanin production and this allele is dominant to all other Mc1r alleles. Each of these mutations seems to localize to the second and third transmembrane domains. This region must be crucial for generating a constitutively active receptor
Given the number of animals that are black due to activating mutations at Mc1r, we analyzed mc1r for variants associated with coat color phenotypes

15. Important genes affecting production traits
Leptin - fat deposition
DGAT1 – milk production and fat
BHGR – milk components
Thyroglobulin - marbling
Calpastatin - tenderness
Calpain - tenderness
Somatostatin -- marbling

16. Myostatin (double muscling)
Belgian blue

17. Double Muscling in cattle
Marchigiana
Piemontese

18. Effect of abolishing GDF8 expression
General increase in muscle mass
Muscular Hyperplasia
up to 86% increase in muscle fibers
and Hypertrophy
up to 20% increase in fiber diameter

19. The way from DNA to functional proteins is much longer than envisaged by the “central dogma”!

20. Control of Gene Expression
Repression of Transcription - Mechanisms:
Binding to promoter elements
Blocking assembly of the preinitiation complex
Topic 8-2

21. Control of Gene Expression
Repression of Transcription - Mechanisms:
Inhibiting binding or functioning of transcriptional activators
Topic 8-2

22. Control of Gene Expression
Repression of Transcription
DNA Methylation
Methyl groups may be attached to cytosine (C5 position)
Methyltransferases
Methyl groups provide a tag
In mammals always part of a symmetrical sequence
Concentrated in CG-rich domains
Often in promoter regions
Methylation of promoter DNA highly correlated with gene repression
Topic 8-2

23. Callipyge “Beautiful buttocks” A mutation which arose in a Dorset Ram
“Polar Overdominance”

24. Polar overdominance
Heterozygote expresses the phenotype but neither homozygote does
Heterozygote only expresses the phenotype if the mutant gene is inherited from the father

26. Positional identification of genes influencing muscle mass …
« Double-muscled » Belgian Blues:
MSTN KO
Hypermuscled Piétrains:
IGF2 upregulation
Callipyge sheep:
Ectopic DLK1 expression
polar overdominance
Hypermuscled Texel:
Patrocles mutation
miRNA
biology

27. A QTL affecting muscle mass maps to OAR2 …
Chromosome 2

28. Texel sheep produce normal levels of normal MSTN mRNA
Sequencing the MSTN ORF from gDNA & cDNA:
no polymorphism.
Northern blot and qRT-PCR:
no obvious qualitative or quantitative difference.

29. Resequencing the MSTN gene identifies 20 non-coding SNPs …
3 Texels – 7 controls

30. G+6723G-A reveals one of « Kellis’s octamer motifs » …

31. -central role of Dicer in RNAi pathway
-cleaves 2nt-3´-overhang-dsRNA; endogenous (pre-miRNA) and exogenous dsRNA into miRNA and siRNA
-products interact with RISC for sequence-specific gene-silencing

32. Expected Finish: Spring 2007
Genomic Sequencing
Launch: Dec. 2003
Expected Finish: Spring 2007

33. International Collaboration
NIH / NHGRI -- $25M
State of Texas – $10M
USDA -- $11M
Australia -- $1M
Genome Canada -- $5M
New Zealand -- $1M
Beef Councils (US, TX, SD) – $0.82M
Project Total = $53M

34. SNP Discovery in the Genome Age
Dominette
...AGCTTTAAGCCATACCTTAGGACATTACCTAGG
GCCATACCTTAGGACATTACCTAGGAGCTTTAAGCCATAC...
...AGCTTTAAGCCATACCTTAGGACATTACCTAGGAGCTTTAAGCCATAC...
Consensus
...AGCTTTAAGCCATACCTTAGGACATTACCTAGGAGCTTTAAGCCATAC...
...AGCTTTAAGCCATACCTTAGGATATTACCTAGGAGCTTTAAGCCATAC...
Martha
SNP

35. Genomic selection
Predicted EBV
Training
EBV

36. From whole to focus devices
DATA
COST
Whole genome
Screening
Statistical path
Patient stratification
High density
Optimization
Metabolic SNP
Reduction amount scrap data
Medium- low density
Focused array
New focusing target
DIAGNOSTIC
Low COST
Limited DATA
EASY-to-USE
Reliability
NUMBER OF SAMPLE
EASY OF USE – REPORT GENERATION
From A. Fischetti, Bioteltech, modified

37. Gain from genomic selection
13/04/2010
Accademia Nazionale delle Scienze detta dei XL

38. Cattle breed
Country
Period
Census population sizea
Effective population size (Ne)
Reference
Holstein
Denmark - 68
Sørensen et al. 2005
Germany
1999
≈ 2,200,000 52
Koenig & Simianer 2006
≈ 3,700,000 49
France
(?)
≈ 2,500,000 46
Boichard et al. 1996
USA
≈ 8,500,000 39
Weigel 2001
Jersey 87
≈ 640,000 53
≈ 550,000 30
Danish red
157
≈ 560,000 47
Japanese black
Japan
Nomura et al. 2001
≈ 530,000 17
Montbéliarde
≈ 700,000
125
Abondance
≈ 65,000
106
Normande
≈ 800,000
Tarentaise
≈ 14,000 27
Taberlet P, Valentini A., Rezaei Hr, Naderi S, Pompanon F, Negrini R, Ajmone-Marsan P. (2008). Are cattle, sheep, and goats endangered species?. Molecular Ecology. vol. 17(1), pp
13/04/2010
Accademia Nazionale delle Scienze detta dei XL