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The dangers of inbreeding in the Arabian horse
Dr. Steven JanssensLivestock genetics
ECAHO, Prague06 feb 2015
Livestock GeneticsDivision Gene Technology, Dep. BiosystemsKU Leuven
http://[email protected]
Kasteelpark Arenberg 30 – 2456B-3001 HeverleeBelgium
Tel: +32 (0)16 32 85 96 Fax: +32 (0) 16 321 994
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Introduction
Diversity between breeds
• The species (Equus Caballus) covers a large number of breeds that differ in many characteristics (e.g. body size)
• Breeds were linked to geographical location � studbooks
• Studbooks organise selection(impose restrictions on reproduction)
• � Selection causes a reduction in the genetic variationin breeds
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Subdivision of the breed may further reducediversity• Sporthorses
show jumping <-> dressage
• In Arabians breeding for:
morphology <-> endurance <-> recreation, ….
keeping original maternal strains pure (RASANs???)
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Why do we need to bother about geneticdiversity?
• Capacity to adapt(= can a population respond to natural and human selection)
• Linked to fitness(= capacity to produce fertile offspring)
� Studbooks need to monitor the genetic diversity of breeds toguarantee survival in the long run
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The origin of geneticvariation
Nuclear DNA
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The horse genome• 62 autosomes + 2 (XX or XY)
• 2,7 109 basepairs (Wade et al. 2009)
• 20322 genes
• 3 106 locations of variation (2012) inthe genome !!!
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Inheritance
• Chromosomes exist in pairs (2n)
• One comes from stallion, other from mare
⇒Horses have 2 copies for every gene, each horse is unique
Genes can have several variants due to mutations �
alleles
⇒Some alleles are no longer functional, some have advantages….
⇒Estimated 1 recessive, deleterious allele/animal
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Mitochondrial DNA…..maternal inheritance
• mtDNA is passed on onlyfrom mare to all the offspring
• Maternal lineages share the same mtDNA
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Genetic variation
• Is caused at the level of the DNA(also mtDNA)
• Genes exist in (many) variants, some advantageous, somedeleterious (1 recessive deleterious allel per individual)
• Genetic variation causes phenotypic variation,but not all variation at DNA level is known (currently)
• Variation affects adaptation capacity and fitness of population
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Measures of diversity
COI – Coefficient of inbreeding (F)
• The probability that 2 genes at any locus in the genomeare identical by descent and results from matingindividuals related by common ancestors (=inbreeding)
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The biological mechanism..
• Mating halfsibs• Each gene has 50%
probability to pass on• F = total prob. for
offspring to behomozygous(red or blue)
1/21/2
1/21/2
P(homozygous red) = 1/2*1/2*1/2*1/2 = 0.0625P(homozygous blue) = 1/2*1/2*1/2*1/2 = 0.0625
F=0.125
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Close matings
Combinations Relationship COI of offspring (F)
Sire - daughter 0.50 0.250
Grandsire -granddaughter
0.25 0.125
Brother-sister(full sibs)
0.50 0.250
Halfsibs 0.25 0.125
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Compute F from a pedigree
Foal
Stallion
Mare
Grandsire
Grandmother
Grandsire
Grandmother
Common ancestor
11
2
m n
F+ +
=
∑
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Find “loops” that connect the sire and dam-side
5 individuals are in the path => F= 0,55=0,0325
Foal
Stallion
Mare
Grandsire
Grandmother
Grandsire
Grandmother
Common ancestor
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Reduction of fitness due to inbreeding
• Increased homozygosity(for desirable traits)
• Unmasking of recessive deleterious alleles(estimates in man and mice indicate that on averageeach individual carries 1 lethal mutation)
• Reduced allozyme variablity(even if genes are not the same, they can work in the same way)
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Inbreeding depression• Mostly on reproduction and fitness traits
(fertility, survival, disease resistance, …)• Typically 1% decrease in fitness per 1% increase in
inbreeding
Example: pregnancy rate
F=0, non inbred: 80%
F=0,125 (parents were halfsibs): 70%
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Inbreeding depression in horses• In Friesians, strong relationship of F of the foal on
« retained placenta » at parturition
• In Polish Arabians, no effect of inbreeding on body measurements (height at withers, chest and cannonbone circumference)
• In Norwegian trotters, negative effect of inbreeding on racing performance
• In Belgian Warmbloods also a negative effect of F on show jumping performance
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Control of inbreeding short and long term
• Avoid high individual F’s
• Monitor and conserve the geneticvariation of the breed
change of average F of the population
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COI in Friesians
Sevinga et al. 2004
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Rate of inbreeding (ΔF) in Friesians
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Inbreeding rate and effective size
• Effectieve population size = number of animals in ideal population with same rate of inbreeding as the studied population
• Rule of thumb:
Ne ≥ 100 or ΔF=0,005 per generation
Ne < 50 danger � ΔF ≥ 0,01 per generation
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Populationunderstudy
foals/yearNe F
Friesian 52392 3000 27 0,15
Belgian Draught 5900 800 80-100 0,03
Arabians(Spain, 2011)
14247 ??? 39 0,09
Arabians(Poland, 2005)
706 ??? -- 0,01
Arabians(Belgium)
4056 350 ?? 0,00
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Ne reflects mating practice in the breed
• Based on number of breeding mares and stallions
1Ne
14Nf
14Nm
Stallions (Nm) Mares (Nf) Ne
Belg. Arabian 836 1860 2307
Belgian Draught 446 384.6 1597
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Ne and mating practice
• Unbalanced use of stallionsand/or mares
V is variance in family size forstallions and mares
Var. Of family size stallions(Vf)
Var. Of family size mares(Vm) Ne
Belg. Arabian 232 3,89 135,3
Belgian draught 1853 2,8 41,6
Ne8N
4 Vf Vm
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Pedigree analysis can reveal much more…
• Number of founders, number of ancestors, number of founder genomes, generation interval ….
• Requires correct and complete pedigree file
�t his feature is expressed in Complete Generation Equivalents
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• Pedigree complete over 4 generations� CGE = 4
• Number of ancestors / generation
21, 22, 23, 24, …
Complete Generation equivalents
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• Incomplete pedigree� CGE = 3.56
• Animals with low CGE� common ancestors less likely
� seem less related
� probably: real inbreeding > calculated
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Pedigree completeness
• Belgian Arabians
CGE = 2,5
� Conclusions forBelgian Arabiansare very preliminary
• Spanish study
CGE = 7,7
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Alternative…..molecular tools
• Use of genetic markers to assess breed diversity
• 2 main indicators of molecular diversity- rate of heterozygosity (H)- allelic richness (Ar)
• We need DNA from a representative group of horses
• Tracking of maternal lineages using mtDNA
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Observedheterozygosity
Expectedheterozygosity
Allelicrichness
Belgian Draught 0,663 0,657 6,7
Arabians(Spain, 2011)
0,533 0,636 3,41
Arabians(Algeria, 2014)
0,718 0,731 6,43
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• Comparison of observed heterozygosity (number of heterozygotes = HO) to the expected heterozygosity (under HWE = HE) � estimate of the degree of inbreeding
• Population inbreeding coefficient (Fis)o Number between -1 and 1
• FIS = 0 � no inbreeding (population HWE)• FIS > 0 � heterozygote deficit (inbreeding)• FIS < 0 � heterozygote excess
� could indicate possible bottleneck, outbreeding,small sample size!
Fis � 1 ���
��
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Relationship between Arabian breeds andstrains
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Maternal lineages can be questioned basedon mtDNA
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Conclusions
The danger of inbreeding in the Arabian horse
• Inbreeding results in:
- inbreeding depression (fitness and reproduction)
- unmasking of deleterious alleles
• In several horse breeds, negative effects of inbreedinghave been demonstrated
• Inbreeding is not only an issue for each individual but should also be handled at population level
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What to do…
• Monitor the breedIf pedigree’s are avalaible this is method of choice. Otherwise, molecular methods can be used
• Ne is a good basic measure to express genetic diversitya value of 100 is desirable for survival of the breed
• Scientific tools exist to optimize breedingaim at equal contributions of parents to next generation
• Carefully think about use of genetic tests !!Exclusion of carrier animals might lead to “bottleneck” thatwill generate new problems in 3 or 4 generations.
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Molecular tools
• Based on markers present in nuclear or mitochondrial DNA
• Requires biological sample and representative number of horses
• No pedigree data needed
• Many applications (within and between breeds)
• Technology evolves fast….applications will follow the coming years. It is a good idea to collect biologicalsamples routinely and more important, record anyinteresting phenotype (disease, color, performance, ….)
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Thank you for yourattention
Acknowledgements
Ministry of the Flemish communitydep. sustainable agricultural development&Flemish Pig Breeding association