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

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Presentation on theme: "Biodiversità animale e sistemi zootecnici Alessio Valentini 13/04/2010 Accademia Nazionale delle Scienze detta dei XL."— Presentation transcript:

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

2 13/04/2010 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

3 13/04/2010 Accademia Nazionale delle Scienze detta dei XL 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) Rules for animal domestication

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

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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-Marsan 1* Proc Biol Sci May 7; 274(1614): 1175–1179.

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

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

9 13/04/2010 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

10 13/04/2010 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)

11 11 Central Dogma of Genetics

12 Breeds of cattle Why so many colors?

13 C33T red chicken (Takeuchi, 1996) S83F chestnut horse (Marklunk, 1996) R151C red hair (Rees, 1997) A240T red pig (Kijas, 1998)  G104 red cow (Klungland, 1995)  C183 yellow mouse (Robbins, 1993) R306ter Irish Setter (Newton, 2000) Molecular causes of Mc1r loss-of-function

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

16 Myostatin (double muscling) Belgian blue

17 Double Muscling in cattle Piemontese Marchigiana

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

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

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

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

22 Topic 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 Control of Gene Expression

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

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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 » … G

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 Genomic Sequencing Launch: Dec 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...AGCTTTAAGCCATACCTTAGGACATTACCTAGG GCCATACCTTAGGACATTACCTAGGAGCTTTAAGCCATAC......AGCTTTAAGCCATACCTTAGGACATTACCTAGGAGCTTTAAGCCATAC......AGCTTTAAGCCATACCTTAGGATATTACCTAGGAGCTTTAAGCCATAC... SNP Martha Dominette Consensus

35 Genomic selection Predicted EBV Training EBV

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

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

38 13/04/2010 Accademia Nazionale delle Scienze detta dei XL Cattle breedCountryPeriod Census population size a Effective population size (Ne) Reference HolsteinDenmark Sørensen et al HolsteinGermany1999≈ 2,200,00052 Koenig & Simianer 2006 HolsteinDenmark ≈ 3,700,00049 Sørensen et al HolsteinFrance (?)≈ 2,500,00046 Boichard et al HolsteinUSA1999≈ 8,500,00039Weigel 2001 JerseyDenmark Sørensen et al JerseyDenmark ≈ 640,00053 Sørensen et al JerseyUSA1999≈ 550,00030Weigel 2001 Danish redDenmark Sørensen et al Danish redDenmark ≈ 560,00047 Sørensen et al Japanese blackJapan Nomura et al Japanese blackJapan ≈ 530,00017 Nomura et al MontbéliardeFrance (?)≈ 700, Boichard et al AbondanceFrance (?)≈ 65, Boichard et al NormandeFrance (?)≈ 800,00047 Boichard et al TarentaiseFrance (?)≈ 14,00027 Boichard et al 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


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