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10/5/12 Megan Rolf Tonya Amen Mark McCully Chromosomes A C T G A G G A G G A G G A G G • Chromosome o Each book consists of multiple sections • Genes C C C A C T G A G G A G G A G G • Genes • Not Genes Chromosomes • 29 pairs Autosomal • 1 pair sex chromosomes (XX or XY) • 1 set from each parent Within your town’s phone book, from one year to another there are a few additions, but most of the book is the same o Each time we go through a generation, there are mutations introduced into the genome We represent DNA like a long string of letters (ACTG) Chromosomes Microsatellite A o Like Smith or Jones o Genetic defect testing o Coat Color BB or Bb DNA Markers o A mutation NEAR the causal mutation o Marker tests Coding vs. Noncoding Your phone book is different from my phone book o Long strings of repeats in the DNA o Genotype = Phenotype o SNP chips • A, T, G, and C o The chromosomes in different families differ from each other o The mutation that causes the phenotype o Typically for performance traits Causal Mutations o Genotype = Phenotype ? DNA Bases Genome o A stack of phone books is like a genome ATGC The Genome! The genome is like a stack of phone books We represent DNA like a long string of letters (ACTG) The image cannot be displayed. Your computer may not have enough memory to open the image, or the image may have been corrupted. Restart your computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again. bb o Common on older parentage panels C T G A G G A G G A G G A G G C C C A C T G A G G A G G A G G 1 10/5/12 We represent DNA like a long string of letters (ACTG) Chromosomes SNPs o Single Nucleotide Polymorphism o Single Base Change in DNA o Like a typo in the phone book o Millions in the bovine genome o Now more commonly used for DNA tests • Easier to assay • Cheaper! Rolf M A C T G A A A G G G A G C T T G A C T G A A A G T G A G C T T G Genes assort independently into gametes o Can’t test directly combinations o Recombination o Track inheritance GT GG AC TT GT GC AC 2003- Human Genome Structure of Sequencing Project Completed DNA Discovered December 2003 Bovine Genome Sequencing Project Commenced 1990- Human Genome Sequencing Project Commenced October 2004 1st Bovine Genome Draft Sequence Complete 2008-50K Chip Available 2010-GE EPDs Genes assort independently into gametes o Every mating can produce 1,152,921,504,606,846,976 genetically distinct full siblings!!! o DNA markers can help us figure out what was inherited by each animal Mid 2000s o First DNA marker test for a production trait o GeneStar Quality Grade o 4 markers by 2007 Mid 2000s-First Commercialized DNA Marker Test for production trait (QG) 2008 2011 2013 o 50K SNP Chip o 770K SNP Chip 2011-770K Chip Available 1970sNCE implemented EPDs Independent assortment o Many possible o Every mating can produce 1,152,921,504,606,846,976 genetically distinct full siblings!!! o DNA markers can help us figure out what was inherited by each animal AT Not the Causal Mutation (unfortunately) 2013 and Beyond: Routine sequencing for high-use genetics? o Genome sequencing-includes all possible DNA markers! o Exome Sequencing o Gene Expression (RNA) 1950 1960 1970 1980 1990 2000 2010 o Rumen Microbes (Microbiome) 2020 Prices are Dropping as amount of data and adoption (volume) increases!!! 2 10/5/12 Now: Genomic Selection Thousands of Markers SNP Markers o Cheap(er) Then: Marker Assisted Selection A few markers Large effects More Options! Picture from msu.edu Parentage Simple Traits: Complex Traits: o Genetic Defect testing Maintaining current prediction accuracy will require constant phenotype collection and retraining with more genotypes Adding more markers on a larger chip will most likely show diminishing returns o 50K to 770K ~3-5% increase in prediction o Genomic data into NCE (for some panels) accuracy (Kachman) o Targeted panels • Strategies for improvement? • GeneMax (not in NCE) + Others o Still markers, not causal mutations o Small Chips o Only a subset of all the mutations in the genome • 9K o Large panels Whole Genome Sequencing o All mutations at one time (could be millions!) • 50K o Not just what is on the chip o Includes causal and rare mutations o Find regions (chip) vs. Find Causal Mutations Sequencing was key to developing all of these tools! 1990-2003: Human Genome Sequencing Project (sequencing) Cost of Sequencing Genomes 3,000 project/budget.shtml) o More than $3 Billion by some estimates! 2003-2005: Bovine Genome Sequencing Project o ~2 years (to get 6x draft assembly) o $53 million (http://www.genome.gov/12512874) o Still working to improve assembly and gene annotations Current Cost for 1 Genome: ~$10,000 Rumored cost for 1 Genome: ~$1,000 o Approximate Cost of Sequencing (in millions) o 13 years o ~$437 Million (http://www.ornl.gov/sci/techresources/Human_Genome/ 2,500 2,000 How much information are we talking about? o 3,200 bases/sheet of paper o 1 copy of each chromosome 1,500 • 3 billion base pairs o 4.6 pallets of paper 1,000 o Each cell has 2 copies of each chromosome 500 Data only, no assembly 0 o Data only, no assembly 1990 2003 2007 2011 2013+ Year http://www.bio-itworld.com/2010/09/28/1Kgenome.html 3 10/5/12 Limited more by data storage requirements and computing power for analysis than by data generation o Are all included in the genome sequence • Develop better marker panels in the future o No need for additional DNA testing Genetic evaluation o Information can be used in genetic evaluation o Like putting together a puzzle with millions of small pieces and no picture to tell you what it looks like o Need to use computer to predict where genes are o Identify mutations Causal mutations o Can also be used to augment DNA testing information for relatives • Fill in the gaps (imputation) Fertility Data repository o Address early embryonic mortality by combo sequencing and DNA chips o Each carrying ~8 recessive lethal mutations o If issues do arise, already have the tools needed to solve the problem quickly Dr. Megan M. Rolf 201h Animal Science Building Stillwater, OK 74078 (405)744-9292 [email protected] 4