CONCEPT OF GENOMIC SELECTION: A NEW BREEDING PARADIGM

PRESENTED BY:

Kush Shrivastava

Traditional breeding methods have been quite successful so

far, without the knowledge of the genes acting on quantitative traits.

Breeders have enhanced production traits in their herds by selecting superior individuals as progenitors for the next generations.

Conventional selection based on individual records, pedigree or progeny performance or family performance.

BREEDING GENES ? VALUE

DNA Markers

Direct Genetic Marker G E N E S M A R K E R

Indirect Genetic Marker

G E N E S

M A R K E R S

Individual observation

Genes

Information from relatives

Phenotype

QTL

Environment

Estimated Breeding Value

Molecular Genetic Markers

Selection

 Requires

prior knowledge of gene alleles or

markers that are associated with the traits of interest.

Explains

only a limited part of the genetic

differences between individuals.

Require

families !

Whole genome SNPs are available for major

livestock species.

Whole genome genetic markers

Segregation of entire genome (and not merely a set of specific regions of interest) can be followed.

Paternal relationships not required !

MARKERS

Genomic selection was first described by Meuwissen

et al. (2001).

Large number of SNPs are required. Distributed throughout the genome. Some might be close to region of interest. Can be used to explain variation in trait(s).

Select on the basis of SNP effects of entire genome.

(Eggen, 2012)

REFERENCE POPULATION

GENOTYPING

PHENOTYPIN G

PREDICTION EQUATION BASED ON SNP

W1X1 + W2X2 + W3X3 + W4X4..

MOST OF THE GENETIC VARIATION IN CAPTURED

SUBSEQUENT GENERATIONS

SELECTION ON CANDIDATES BASED ON GEBV ONLY (Hayes et al., 2009, 2013)

Case I: MAS consider a single SNP marker with allele A&B

Allele A: +4 AND Allele B: - 4

Animal no. 1 Marker (SNP) allele AA Value +8 MAS- EBV +8

2
3

AB
BB

0
-8

0
-8

Case II: Genomic selection - Consider 4 SNPs ; allele A vs. B SNP 1 Allele A: +4 AND Allele B: -4 SNP 2 Allele A: +2 AND Allele B: -2 SNP 3 Allele A: +1 AND Allele B: -1 SNP 4 Allele A: -3 AND Allele B: +3

(Eggen, 2012)

 Genomic

selection builds on existing breeding

programs.
Better

selection accuracy while reducing the

generation interval.
In

cattle, more than 15 countries are now using

genomic breeding values.

Schaeffer (2006) showed that using genomic selection, the genetic gain per year could be doubled in dairy cattle.
Bull A is born and is selected based on EBV

Bull A is put to progeny testing

Progeny of Bull A is born

Progeny of Bull A calves

Milk production data of progeny of Bull A become available.

Sons of Bull A are born

0 yrs

1 yrs 3mo

2 yr

4 yr

4 yr 6 mo

5 yr 3 mo

EBV of bull A is estimated using progeny performance & can be used as sire

Generation Interval = 63months Fig. Timeline of a traditional artificial insemination breeding program based on progeny testing. EBV = estimated breeding value.
(Schefers and Weigel, 2012)

Fig. Timeline of an aggressive artificial insemination breeding program based on the use of genomic bulls as sires of sons. GEBV = genomic estimated breeding value; EBV = estimated breeding value.
Progeny of Bull B reaches sexual maturity and can be used as sire of sons. Milk production data from progeny of bull B are available for calculation of EBV

Bull B is born & selected on basis on GEBV

Bull B reaches sexual maturity & can be used as sire

Progeny of Bull B is born

Grandson of Bull B are born

Great grandson of Bull B are born

0 yrs

1 yrs

1 yr 9 mo

2 yr 9 mo

3 yr 6 mo

4 yr 6 mo

5 yr 3 mo

Generation Interval = 21 months

Grandson of Bull B reaches sexual maturity and can be used as sire of sons

(Schefers and Weigel, 2012)

Started since 2008 in United States, Canada, New Zealand, France, Netherlands.

Genomic predictions values were more accurate than

traditional pedigree index, specially for low for low

heritability traits
(Van Raden et al. 2009)

Reduction of breeding bulls due to higher selection intensity in NZ.

(Spelman et al. 2010)

Genomic selection has not yet been implemented in small ruminants.

Pilot genomic evaluations have been implemented in

New Zealand.

SNP chip still not available for goats. However, due to limitation in current data recording schemes - GS might produce inferior results.
(Van der Werf, 2009)

Pig breeding Still under research & experimentation.

SNP chips for pig is available.

(Ibaez-Escriche and Gonzalez-Recio., 2011)

GI is low in pigs, therefore, to increase response, GS will be effective for traits with low accuracy of selection (e.g., low heritable traits, slaughter traits etc.) Population size for low heritable traits Approx. 10 times larger.
(Goddard, 2009)

Increase of 68% in accuracy of the breeding values of the experimental population over traditional selection.
(Forni et al. 2010)

(Ibaez-Escriche and Gonzalez-Recio., 2011)

Sequenced genome available in 2004.

(Hiller et al., 2004)

Three SNP panels of sizes 6, 12 and 42 K are available.

Experimental GS results are available.

(Long et al. 2007; Gonzlez-Recio et al. 2008 ,2009)

Why should commercial breeder takes up GS ? Cost effectiveness yet to be verified !

(Ibaez-Escriche and Gonzalez-Recio., 2011)

Sequencing data of almost all important livestock species

is available.

(Fan et al., 2010; Eggen, 2012)

1HD = High Density; LD = Low Density 2 Illumina Inc., San Diego, CA; Affymetrix, Santa Clara, CA.

(Eggen, 2012)

Low Density = Low Cost; lesser genome coverage

High Density = More Cost; more genome coverage

Habier et al. (2009) and Weigel et al. (2009; 2010) confirmed small losses in accuracy on the genomic predictions on using LD chips.

Strategy I - Weigel et al. (2009), select only based on SNPs that show strong association thus might be neglecting small effects.

60000 SNP

2242 SNP

Trait

Goddard and Hayes (2008) : Ancestors are genotyped with dense panels

and the selection candidates are genotyped with standard low-density

panels

But it require pedigree, not a big deal for dairy cattle in developed nations. Success depends on 2 factors (Goddard, 2009):

Size of the founder Choice of the ancestor population

700000 SNPs

Reference population

Weigel et al., (2010) Utilizing genomic information from ancestor or relatives, there is only 4 % reduction in estimated breeding value by using LD chips as

2000 compared to HD chips. SNPs

High Density SNP map

(Weigel et al., 2010)

(Buch et al. 2012 )

Planned mating Based on approx.7 generation) by using genetic relationship current population as reference

Re- estimation of GEBV (after

High density SNP chips Up to 7 lakh SNPs Whole genome sequencing & re- sequencing.
Sequence based selection

Inclusion of sequence data

40 % gain in accuracy of predicted breeding value
Accuracy maintained up to 10 generations (Meuwissen and Goddard, 2010)

Livestock have large numbers of symbionts, (bacteria and protozoa) in digestive tract. Affect some key traits feed conversion efficiency.

Rumen microbiome profile is important methane

production. Beef cattle more methane production. Emission depends upon type of ruminal microbes
(Johnson and Johnson, 1995)

Microbes carried by an animal depend on features of the animal (to some extent).

Can be regarded as part of the phenotype of the animal and subject to genetic variation.

Bensen et al., 2010; Identified QTL in mice affecting gut mircoflora.

Selection of cattle for desirable gut microflora.
Look for genome wide SNPs that favour the desirable gut ecosystem

Manipulation of microbes be external effects (like feed etc.)

(Hayes et al., 2013)

Treated genome as a Black Box Not necessary to know what's INSIDE it. No credit for function of individual gene.

Markers

GENES !!
Function of each gene (& the variation within)

Phenotype Understanding of the biology of the animal that makes phenotypic variations significant E

(Eggen, 2012)

Limited by the absence of programs that record phenotypes on pedigreed animals

lack of evaluation or national testing programs to assess the genetic value of germplasm.

Genomic approaches should help in identifying critical populations for preservation

Conservation of some local well-adapted breeds. Genomics = manage what we can measure Collecting a minimum number of phenotypes in the field is one of the critical and challenging steps to further deployment of genomic selection in developing countries. (Eggen, 2012)