Why genomics works and what is coming

G.R. WiggansAnimal Improvement Programs LaboratoryAgricultural Research Service, USDA Beltsville, MD

[email protected]. WiggansADSA 18th DISCOVER Conference – 2009 (1)

Why genomics works and what is coming

G.R. WiggansADSA 18th DISCOVER Conference – 2009 (2)

What is genomics?

Study of the effects of an animal’s genes

Evaluations are based on DNA markers

Single-nucleotide polymorphism (SNP) markers are abundant and cheap to read

Illumina BovineSNP50 BeadChip provides genotypes for >50,000 (50K) SNP

Possible genotypes across 2 chromosomes at each SNP are AA, AB, and BB


What is whole-genome selection? Many markers used to track inheritance

of chromosomal segments

Impact of each segment estimated for each trait

Estimates combined with traditional predicted transmitting ability (PTA) to produce genomic evaluation (GPTA)

Animals can be selected shortly after birth


What is a SNP?

Place on the chromosome where animals differ in their DNA nucleotides (A, C, T, or G)

Usually not part of the gene that controls a trait – quantitative trait locus (QTL)

With enough SNPs, association between SNP and QTL alleles allows useful genetic evaluation

SNPs chosen to be distributed evenly and have both alleles well represented in the population


Source of genomic evaluations

DNA extracted from blood, hair, or semen

43,385 SNPs evaluated

SNP effect is difference in PTA from having 1 more A (BB v AB or AB v AA)

Genomic evaluation combines SNP effect estimates with existing parent average (PA) or PTA


Genotyping preparation

Nominate animal for genotyping

Collect hair, blood, or semen from animal Blood may not be suitable for twins

Send to laboratory for DNA extraction

Transfer DNA to BeadChip (12 samples/chip) for 3-day genotyping process


Genotyping

Read red/green intensities from chip

Call genotypes from intensity file

Check genotypes: Duplicates Parent-progeny conflicts Wrong Breed Wrong sex


Clustering adjustment … before

86%

callrate


Clustering adjustment … after

100%

callrate


10001112200200121110111121111011110011211000201220022201111202101200211122110021112001111001011011010220011002201101120020110102022212112210201001110001122022122211202112012020100202202000021100011202011221112111022011110000212202000221012020002211220111012100111211102112110020102100022000220100020110000220221102211210112111012222001211212220020002002020201222110022222220022121111210021111200110111011200202220001112011010211121211102022100211201211001111102111211021112200010110111020220022111010201112111101120210210212110110221220012110112110120220110022200210021100011100211021101110002220020221212110002220102002222121221121112002011020200122222211221202121121011001211011020022000200100200011110110012110212121112010101212022101010111110211021122111111212111210110120011111021111011111220121012121101022202021211222120222002121210121210201100111222121101

Genotype for Elevation

Chromosome 1


102122210102102101110211011211221121100220200022202000202022000002200202222022020000200202222220000202222000002202000020022002000000222200022220000000000020222022002000222020222220002202222222220000200220202220200020002200000000220222000000220020200022220020200200202022202222222202220200020220220222202022202020202200022002220220022200000220200002002002000200222220002222020200222002220200002020000002222202020000200200222200020220222200220002222022002222020200022022022220022200220002002202000002200220222000022000022000222202002222000220020020202202000222000222002220220220000022022002002002022000200022220220022200202202002222022200000202200020200202020002200220000022022200202220200022002000200022002002000200220222220022022000200002000200002022002022020020000222000022200200020022200002202200200220022022020202020202000222020002202002022022202200002020200002020200022222200222200020022022220000020220020200202022022020200002000200220220002200

Genotype for inbred bull (Megastar) Chromosome 24

Double grandso

n of Aerostar


What can go wrong

Sample does not provide adequate DNA quality or quantity

Genotype has many SNPs that can’t be determined (90% call rate required)

Parent-progeny conflicts Pedigree error Sample ID error Laboratory error Unrelated animal qualifies as parent or

progeny


Parent-progeny conflict

Parent

10212002101201211001020120100

Progeny

10202010100200221001120120220


Bull

202220200002022220002020222020202

Cow

120120121222201011102221021021202

X chromosome


Data & evaluation flow

Animal Improvement

Programs Laboratory,

USDA

AI organizations,

breed associations

Dairyproducers

DNAlaboratories

samples

samples

samples

genotypes

nominationsevaluations


Protein PTA

0

10

20

30

40

50

1990 1995 2000 2005 2010

Birth year

Pro

tein

PT

A (

lb)

Genomic

Traditional

Traditional PA


Protein reliability

0

20

40

60

80

100

1990 1995 2000 2005 2010

Birth year

Pro

tein

rel

iab

ilit

y (%

)

Traditional

Genomic

Traditional PA


0

250

500

750

1000

1250

1500

0 10 20 30 40 50 60 70 80 90 100

Protein reliability (%)

Bu

lls (

no

.)Reliabilities for young bulls

Genomic PTA

Traditional PA


Actual results from 50K chip

High correlation between genomic merit in November 2004 and August 2009 merit that includes performance

Bull with highest genomic net merit in November 2004 (Man O Man) now ranks 4th of 1,925 bulls

Bull with highest genomic net merit in January 2009 (Freddie) now ranks 2nd


Use of genomic evaluations

Determine which young bulls to bring into AI

Aid in selection of mating sires

Increasing impact on bull dam selection

Market semen from 2-year-old bulls


Updates between official evaluations Genomic evaluations calculated every 2

months

Not released for animals that already have an official evaluation

Evaluations of new animals distributed to owners Females by breed associations Males by NAAB

Usually 2,000 new genotypes included


Impact on producers

Young-bull evaluations with accuracy of early 1st-crop evaluations

AI organizations marketing genomically evaluated 2-year-olds

Bull dams likely to be required to be genotyped

Rate of genetic improvement likely to increase by up to 50%

Progeny-test programs changing


International implications

All major dairy countries investigating genomic selection

Interbull working on how genomic evaluations should be integrated

Collaboration within Europe to share genotypes

Prediction accuracy continues to increase with increasing numbers of predictor animals

Importing countries must change rules to allow for genomically evaluated young bulls


Possible selection of embryos

In vitro fertilization of embryos from immature animals Further reduces generation

interval Not yet feasible

Frozen, genotyped embryo market Cost of genotyping < cost of ET Could replace AI if accuracy high


Best chromosome 1

-40

0

40

80

120

160

X 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

Chromosome

Net

mer

it, $

Co-Op Boliver Lisha-ET


Best chromosome 2

-40

0

40

80

120

160

X 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

Chromosome

Net

mer

it, $

Kellercrest Earnit Hank


Best 30 chromosomes

-40

0

40

80

120

160

X 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29

Chromosome

Net

mer

it, $

Genomics Extraordinare

Overall net merit = $3,148


What may be coming

Approximate (impute) genotypes of missing ancestors to increase predictor population

Increase number of SNPs or even use entire DNA sequence

Impute 600K SNP from current 50K chip

Impute 50K from lower cost, lower density chip


Application to more traits

Animal’s genotype good for all traits

Traditional evaluations required for accurate estimation of SNP effects

Traditional evaluations not currently available for heat tolerance

Research populations could provide data for traits that are expensive to measure Estimates of SNP effects must be

appropriate for target population


Implications

Extraordinarily rapid implementation of genomic evaluations

Young-bull acquisition and marketing now based on genomic evaluations

Genomic evaluations may allow more cows from commercial herds to be used as bull dams


Financial support

National Research Initiative grants, USDA NAAB (Columbia, MO)

ABS Global (DeForest, WI) Accelerated Genetics (Baraboo, WI) Alta (Balzac, AB) Genex (Shawano, WI) New Generation Genetics (Fort Atkinson, WI) Select Sires (Plain City, OH) Semex Alliance (Guelph, ON) Taurus-Service (Mehoopany, PA)

Holstein Association USA (Brattleboro, VT) American Jersey Cattle Association

(Reynoldsburg, OH) American Brown Swiss Association (Beloit, WI) Agricultural Research Service, USDA

Why genomics works and what is coming

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