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Jared E. Decker State Beef Genetics Specialist https://www.facebook.com/SteakGenomics.

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Presentation on theme: "Jared E. Decker State Beef Genetics Specialist https://www.facebook.com/SteakGenomics."— Presentation transcript:

1 Jared E. Decker State Beef Genetics Specialist DeckerJE@missouri.edu http://web.missouri.edu/~deckerje/extension http://steakgenomics.blogspot.com/ https://www.facebook.com/SteakGenomics 1

2  ~100 genes where one copy is functional and the other is broken  ~20 genes where the broken copy is a lethal mutation  Called Loss of Function mutations 2 Science Vol. 335 no. 6070 pp. 823-828 DOI: 10.1126/science.1215040

3 Inconvenient Genetic Truth  Everybody has genetic defects!!! 3 Even the most beautiful people in the world

4 Inconvenient Genetic Truth  Everybody has genetic defects!!! 4 Even the most caring people in the world

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6 What happens when a broken gene is inherited from the father and the mother?  Genetic abnormality  Spontaneous abortion 6

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8 Dog BreedCanine DiseaseGene BasenjiRenal Fanconi SyndromeFAN1 Chinese CrestedMultiple Systems DegenerationSERAC1 Kerry Blue TerrierMultiple Systems DegenerationSERAC1 Jack Russell TerrierSpinocerebellar AtaxiaKCNJ10 BasenjiProgressive Retinal AtrophySAG Standard SchnauzerDilated CardiomyopathyRBM20 Australian ShepherdNeuronal ceroid lipofuscinosisCLN8 Soft Coated WheatenParoxysmal dyskinesiaPIGN Tibetan TerrierProgressive retinal atrophyFAM161A Chinese CrestedNeuronal ceroid lipofuscinosisMSFD8 Causal mutations identified at Mizzou by whole genome sequencing

9 Dog BreedGeneHuman Disease BasenjiFAN1Karyomegalic interstitial nephritis Chinese CrestedSERAC1MEGDEL syndrome † Kerry Blue TerrierSERAC1MEGDEL syndrome † Jack Russell TerrierKCNJ10SeSAME syndrome ‡ BasenjiSAGOguchi disease 1 Standard SchnauzerRBM20Dilated cardiomyopathy 1DD Australian ShepherdCLN8NCL8/Northern epilepsy Tibetan TerrierFAM161 A Retinitis pigmentosa 28 Soft Coated WheatenPIGNMCAHS syndrome 1 ≠ Chinese CrestedMSFD8Neuronal ceroid lipofuscinosis 7 A documented human disease corresponds to each of the canine diseases caused by mutations identified by whole genome sequencing

10 Broken Genes in Cats TRAITBREEDGENE Vitamin-D dependent rickettsDSHCYP27B1 Chediak-Higashi syndromePersianLYST AtrichiaSphynxKRT71 HypotrichiaDevon RexKRT71 Melanocyte migrationBirmanKIT HypotrichiaCornish RexP2RY5 HypotrichiaSelkirk RexKRT71 Craniofacial defectBurmeseCART1 HypokalemiaBurmeseWNK4 Gangliosidosis 1 and 2Korat / BurmeseGBL1 / HEXB PRAAbyssinianCRX / CEP290 PKDPersianPKD1 Pyruvate kinase deficiencySeveralPKLR Hypertrophic cardiomyopathyMaine Coon / RagdollMYBPC Lipoprotein lipase deficiencySeveralLPL Spinal muscular atrophyMaine CoonLIX1-LNPEP Mutations found by Lyons Cat Genetics lab

11  Full genome sequence 99 cats  Centralized and publically available  Any breed or population of cat worldwide ▪Interesting trait or health issue ▪12 cats races ▪24 major breeds ▪Rare breeds ▪Other felids

12 What happens when a broken gene is inherited from the sire and the dam?  Genetic abnormality  Spontaneous abortion 12

13  Some we know about  Some we don’t 13 KNOWN Even the most beautiful cattle in the world

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15  DNA tests can now be developed in a few months  With DNA tests available, frequency of the known genetic defect rapidly decreases  Now we can manage genetic defects

16  There are more than 35 genetic defects in cattle with a DNA test 16

17  Documented in 1950’s  Became prevalent in 2000’s due to heterozygotes having straight hind limbs and long shaggy hair  Present in Galloway, Shorthorn, %Maine-Anjou, %Chianina, and other breeds with open herd books  Single autosomal recessive 17 Beever, Jonathan Edward, and Brandy Michele Marron. "Screening for the genetic defect causing tibial hemimelia in bovines." U.S. Patent 8,158,356, issued April 17, 2012.

18  Due to ~46,000 bp deletion in ALX homeobox 4 (ALX4) gene, a transcription factor expressed in developing bones, limbs, hair, teeth, and mammary tissue.  “Note the twisted hind limbs and the large abdominal hernia. The calf also had a meningocele and cryptorchidism.” (Whitlock, Kaiser, and Maxwell, 2008) 18 Beever, Jonathan Edward, and Brandy Michele Marron. "Screening for the genetic defect causing tibial hemimelia in bovines." U.S. Patent 8,158,356, issued April 17, 2012.

19  Present in Maine-Anjou, %Chianina, and Shorthorn  Lethal autosomal recessive  “Note the severe anasarca.” (Whitlock, Kaiser, and Maxwell, 2008) 19

20  Also known as “curly calf”  Recognized by American Angus Association as a genetic defect on September 16, 2008.  Recessive mutation  Twisted spin, contracted legs, light muscled 20

21  Recognized by American Angus Association as a genetic defect on June 12, 2009.  Recessive mutation  Calves carried to near term  Weigh 25 to 35 lbs  Head is severely enlarged  Bones of skull are malformed  No brain tissue is present and skull is filled with fluid 21

22  In Hereford cattle  Autosomal recessive  Calves experience seizures, especially during stress such as temperature or handling 22

23  Also known as “Marble Bone Disease”  In Red Angus  Cattle are typically born dead or die in first 24 hours  Bones are extremely brittle and lower jaw is short  ~2721 bp deletion in the SLC4A2 gene affecting exons 2 and 3 23

24  In Hereford cattle  Autosomal recessive  8 base pair deletion mutation in first exon of the keratin 71 (KRT71) gene  Complete or partial loss of hair 24

25  Also known as “Fawn Calf”  Nonlethal recessive genetic abnormality  Upper limb joints have a reduced range of motion 25

26  Polymelia  Most die as embryos 26

27 The Truth: Every Living Thing Is A Genetic Defect Carrier 27

28 Seedstock:  Test at-risk breeding stock for genetic defects  Do we know the pedigree of the animals?  Are there carriers in the pedigree? 28

29 Commercial:  Crossbred  Outcross  Avoid using the same bloodlines  Test at-risk breeding stock for genetic defects  Do we know the pedigree of the animals?  Are there carriers in the pedigree? 29

30  Create a documented record of what happened  Take a picture or video of affected calves  Freeze the entire animal if possible, otherwise preserve the abnormal body part  Obtain 40 hair bulbs from the calf, dam, and sire 30

31  Breeders should contact their breed association and local veterinarian  Need intensive description of phenotype  The majority of abnormalities are caused by the environment, not genetics 31

32 What happens when a broken gene is inherited from the sire and the dam?  Genetic abnormality  Spontaneous abortion 32

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34  Sequence the genomes of 165 registered bulls  We will discover hundreds of broken genes  Most embryonic lethals  Breeds co-sponsoring sequencing:

35  Sequencing completed for all 165 of the animals  Currently running data thru analysis pipeline

36  We have already analyzed the genomes of 11 bulls 36

37  We have already analyzed the genomes of 11 bulls  Identified 176 possibly lethal alleles 37

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40  Predictions are sums of marker effects  For lethal mutations  Homozygous normal: effect is 0  Heterozygous lethal: effect is -q i f  Allows publication of a fertility EPD 40

41  Avoid mating carriers of the same lethal mutation  Will also manage  Genetic merit  Genetic diversity  Built upon economic selection indexes 41

42  See abnormal calf  Bury calf 42

43  Report abnormal calves  Collect data  Create a test  Manage the defect 43

44  Sequence influential AI sires  Create tests for LOF mutations  Manage the mutations while accounting for overall genetic merit 44

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46 Thank You! Questions? 46 http://web.missouri.edu/~deckerje/extension http://steakgenomics.blogspot.com/ https://www.facebook.com/SteakGenomics


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