Marker assisted selection

Artificial Selection
• Artificial selection occurs whenever humans
choose to breed from certain animals and not
from others.
• The aim is to select as parents those animals
that have the highest breeding value for the trait
of interest, out of all the candidates available for
selection, so as to achieve the highest possible
average performance for that trait in the
offspring of selected parents.
• The true breeding value of an animal for a
particular trait is unknown, but can be estimated
from phenotypic values.
• Animals are ranked according to estimated
breeding value (EBV) for the trait of interest and
those at the top of the list are selected.
• In classical genetic improvement programmes,
the sources of information used in calculation of
EBVs include:
- own phenotype
- information from relatives
- information from correlated traits
• Selection is carried out based on the observable
phenotypes without knowing which genes are
actually being selected.
 Marker-assisted selection (MAS)
• MAS - Use of information from genetic markers
to help make selection decisions of animals for
genetic improvement.
• This is done in a manner that exploits both
known major genes and all unknown genes.

• Technologies
- MAS - Select on a molecular marker linked to
the gene of interest = indirect marker

• Genotypic assisted selection (GAS) - select

directly on the gene of interest = direct marker
• Genetic markers are identifiable DNA
sequences, found at specific locations of
the genome, and transmitted by the
standard law of inheritance from one
generation to the next.
• Genetic markers are “landmarks’ at the
genome that can be chosen for their
proximity to the quantitative trait loci (QTL)
of interest.
• We cannot actually observe inheritance at
the QTL itself, but we observe inheritance
at the marker, which is close to the QTL.
• Different kinds of DNA markers exist : restriction
fragment length polymorphisms (RFLPs),
Random amplified polymorphic DNA (RAPDs),
amplified fragment length polymorphisms
(AFLPs), Microsatellite and Single nucleotide
polymorphisms (SNPs).
• These markers allow high-density DNA marker
maps to be constructed for a range of livestock
species.
• Using the marker map, putative genes affecting
traits of interest can be detected by testing for
statistical associations between marker variants
(alleles) and the trait of interest.
• The idea behind marker assisted selection is
that there may be genes with significant effects
that may be targeted specifically in selection.
• Some traits are controlled by single genes (e.g.
genetic disorders and hair colour).
• Most traits of economic importance are
quantitative traits that are controlled by many
genes, called quantitative trait loci (QTL),
together with environmental factors (e.g. Milk
yield and growth rate in animals).
• Some of these genes have a larger effect while
others have small effects on the phenotype
observed.
• Finding the actual genes is difficult.
• In the first instance markers linked to the genes
(generally those of larger effect) are identified,
then MAS is carried out.
• The success of MAS is influenced by the
relationship between the markers and the genes
of interest.
• Suppose there is a marker M (with two alleles M
and m) known to be located on a chromosome
close to a gene of interest Q (with a variant Q
that increases milk yield and a variant q that
decreases yield), that is not yet known.
• If an individual has M and Q on one
chromosome and m and q on the other
chromosome
- Any of its progeny receiving the M allele
will have a high probability (depending on
how close M and Q are to each other on
the chromosome) of carrying the
favourable Q allele. This will be preferred
for selection purpose.
- Any of its progeny inheriting the m allele
will have inherited the unfavourable q.
This will not be preferred for selection.
 Types of relationship between the
markers and the genes of interest
(i) The marker is located within the gene of
interest (i.e. within gene Q)
- The marker is the causative of mutation
- By following inheritance of M alleles,
inheritance of the Q alleles is followed directly.
- Selection basing on the marker is referred as
gene-assisted selection (GAS).
- Identifying the gene and causative mutation
can take many years.
- It is more difficult for quantitative traits than for
qualitative traits because causality is
difficult to prove.
(ii) The marker is in linkage disequilibrium (LD) with
the gene of interest (Q) throughout the population
- LD is the tendency of certain combinations of
alleles (e.g. M and Q or m and q) to be inherited
together.
- Population-wide LD can be found when markers
and genes of interest are physically very close to
each other (within 1 to 5 cM) and/or when
breeds/lines have been crossed in recent
generations.
- Selection using these markers is called LD-MAS.
- The LD markers can be identified using
candidate genes or fine-mapping
approaches.
(i) The marker is in linkage equilibrium (LE) with
the gene of interest (Q) throughout the
population
- In a population that is in LE, alleles at two loci
are randomly assorted into haplotypes i.e. a
chromosome that carry M allele is no more
likely to carry Q allele than the chromosome
that carry m allele.
- Selection using these markers is called LE-
MAS. It is the most difficult situation for
applying MAS.
- If the marker and QTL are in LE, there is no
value in knowing an individual’s genotype
because it provides no information on QTL
genotype.
• The LE markers can be detected on a genome-
wide basis by using breed crosses or analysis of
large half-sib families within the breed.
• Such genome scans require only sparse marker
maps (15 to 50 cM spacing) to detect most QTL
of moderate to large effects.
• The three types of marker loci differ in their
application in selection programmes.
• Direct markers and, to a lesser degree, LD
markers, allow for selection on genotype across
the population because of the consistent
association between genotype and phenotype.
• LE markers allow for different linkage phases
between markers and QTL from family to family.
 Some points about MAS
• MAS is less accurate that GAS
• The accuracy of MAS depends on
recombination frequency (linkage
distance) between the marker and QTL.
• MAS requires progeny testing to
determine linkage phase of QTL and
marker in each family.
Requirement for successful application of MAS

• Gene mapping – identification of genes and

DNA markers and their chromosomal location
• Marker genotyping – genotyping of large
numbers of individuals for large numbers of
markers
• QTL detection – detection and estimation of
associations of identified genes and genetic
markers with traits of economic importance.
• Genetic evaluation – integration of phenotypic
and genotypic data in statistical methods to
estimate breeding values of individuals.
• MAS – use of genetic markers information in
selection and mating programmes.
Traits which will benefit most Marker
assisted selection

• Traits that require slaughter to be

measured e.g. carcass traits
• Traits that are measured on one sex only
e.g. milk production
• Traits that are measured late in life e.g.
lifetime fecundity
• Traits that are difficult or expensive to
measure e.g. disease resistance
Relative advantage of MAS/GAS over
traditional selection is higher if
• Heritability is low - the value of information on
individual QTL tends to be higher because
accuracy of breeding values is increased by a
relatively larger amount.
• The trait of interest cannot be measured on one
sex – marker information gives a basis to rank
animals of that sex.
• The trait is not measurable before sexual
maturity - marker information can be used to
select at a juvenile stage.
• The trait is difficult to measure or requires
sacrifice (as with many carcass traits) - marker
information can be used instead.
• The QTL is of larger effect
• QTL and marker are closely linked
• Mode of gene action is non-additive
• The favourable allele is initially rare
 Importance of Phenotypic Data

• The need for phenotypic data won’t

disappear because of genetic markers
• Many small QTL will remain undetected
• Marker/QTL relationships must be re-
estimated and verified regularly
• Changes in other traits must be
monitored
 Response to MAS over time
• Response due to genetic change in individual
QTL is limited – stopping when ideal variants are
widespread throughout the population.
• This happens more quickly where just one or
two closely marked QTL are involved for the trait
of interest, and frequencies of favourable
variants are not low to start with.
• Of course the actual benefits of favourable
variants will continue.
• It is the level of impact in the population that is
limited - in contrast to 'normal‘ selection where
genetic gains usually appear to be unlimited.
Short and long term effects of
Marker Assisted Selection
Marker-assisted introgression
• Use of genetic marker to speed up
introduction of a gene of interest from one
breed to another.
• Bring in desired allele(s) from a donor breed
to recipient breed and use markers to select
crossbreds/backcrosses carrying it
 Introgression strategy
QTL(s) for introgression identified in a donor animal

Donor Animal x Recipient Animal

F1 Offspring x Recipient animal

Back-cross 1

2 – 6 generations of back-crossing
with the recipient animals

Back-cross 5

Inter-cross (Back-cross 5 x Back-cross 5)

7 -11 generations of intercrossing

Inter-cross 5 (new genotype)

 Some points about MAI
• A large number of animals are required
(≥500 animals in each generation).
• Its important to trace the QTLs so that
they are retained while the recipient
genome is recovered.
• Risk – epistatic effects: performance of
QTL identified in the donor breed cannot
be predicted in advance in the recipient
breed.