Healthy dog breeds Diversity in dog breeds Pieter

Healthy dog breeds Diversity in dog breeds Pieter Oliehoek www. dogsglobal. com info@dogsglobal. com

What will we talk about Variable presentation…. ! • Short and simple course: genetics. . And then: • Diversity within dog breeds • • • Population size Founders FGS …. FGE … Inbreeding • Dog breeds lost dramatic amount of diversity • Breeding in practice - Diversity • • One-time litters Mean Kinship • • Dogs Global Database Crossbreeding (other breeds or animals from the region)

Interactive !!!!!

5 Statements Most software used by breeders work with 10 generations 1) For inbreeding calculations 10 generations is enough. True? ? Yes / No

5 Statements Many test’s for diseases are required before breeding is allowd 2) Diseases within a breed can be avoided by selecting against the affected animals. True? Yes / No

5 Statements The most practised measure taken is to avoid inbreeding of a litter (by disallowing parent offspring matings and check inbreeding of a litter before a mating 3) By avoiding inbreeding, we keep the diversity of the breed. True? Yes / No

5 Statements 4) If you don’t select against the wrong traits (like cataract) these traits will be spread over the population True? Yes / No

5 Statements Almost all breeds require X-ray for HD before being used in breeding 5) HD-testing is necessary or at least not harmful for a breed True? Yes / No

Disney / Shakalin Husky

Shakalin Husky / Canadian Inuit Dog Eight below (Disney) Ainu (people)

What is a breed? …. And what do you want to preserve? ? Breed- characteristics Healthy animals Exterior Behaviour ▪ Independent / good hunter Animals having same origin subspecies; region; country Possibilities to improve he breed

Short Course on Gene(tic)s 20. 000 -pairs) loci (gene in the dog ▪ Humans: 26. 000 For each ‘locus’ 2 alleles Questions ? !? !? !

The alleles (genes). . 1: A||a 2: B||b 3: C||c 4: D||d 5: D|| . . : D|| 20. 000+ | | => a 1 Ᾰ ᾶ ἀ a 2 => β b 1 Б B 2 => c 1 … … 25 Each different form of a gene: is called: “allel” Warning I often use: “different genes” !!! meaning: alleles

Genes in the population 20. 000 loci (genes) in the dog Half of each parent Just 100 to 1000 loci (genes) determine the breed Only 5 – 10 loci are most influential 19. 000 genes (loci) are NOT influential. . But they CAN be ‘ill’!!! Each mammal has 5 recessive genetic diseases

What is diversity (of the breed / population) Number of animals Population size / Founders Number of unique alleles Founder Genome Surviving (FGS) ▪ Estimated in “Number of animals” Spread of alleles / relatedness Founder Genome Equivalents (FGE) ▪ Estimated in “Number of animals en” Inbreeding

Founders Highly relevant for populations in captivity Animals that are unrelated to each other Own parents often unknown, but not necessarily All other animals descend from these founders • • In zoos: animals from the wild Icelandic Sheepdog: animals from remote area’s Wetterhoun => Frisian Hunters Leonberger => companion animals / working animals (old Saint Bernard type) Crossbreeding with another breed is also a ‘founder’ There is never more diversity than there was present in the founders animals

The alleles. . F 1 F 2 1 | | 2 | | 3 | | | | 20. 000+ F 3 || || => Founders: each gene unique => a 1 Ᾰ ᾶ a ἀ a 2 => β b 1 B Б b B 2 => c 1 … … 6 => etc. . !!!

Zoo populations Population: number of animals Founders: number of original unrelated wild caught animals species Population Founders FGS FGE Cheetah 1640 1590 366 11 Bonobo 200 103 52 60 Lesser Panda 550 279 50 21 Okapi 269 165 24 18

Dog breeds Population: number of animals Founders: number of original unrelated animals en

Founders Wetterhoun Registration Nr Name Gender Year Pups Rep NHSB NR 34568 Juno Reu 1943 5 5 282. 5 30. 8% NHSB NR 40847 Mollie Teef 1942 3 3 167. 9 18. 3% 49. 1% NHSB NR 5 Sannie Reu 1945 4 2 132. 1 14. 4% 63. 5% NHSB NR 17 Sophie Teef 1943 1 1 90. 3 9. 8% 73. 4% NHSB G 0 275767 Fijkje Teef 1959 5 2 90. 2 9. 8% 83. 2% NHSB G 0 275897 Ferdau Teef 1956 5 1 82. 8 9. 0% 92. 2% NHSB G 0 154319 Mollix Reu 1946 2 1 36. 1 3. 9% 96. 2% NHSB NR 1 Reu 1942 2 1 18. 0 2. 0% 98. 1% Teef 1946 7 2 17. 0 917 1. 9% 100. 0% Jentje NHSB G 0 155121 Marina 8 Founders Totaal: Contri Perc. 100% Som:

Founders Nederlandse Kooikerhondje Nummer Name DG-P 1 Mother of Biffie VHNK 21 Bobbie VHNK 132 Bennie (uit Friesland) VHNK 119 Tommie (uit Friesland) DG-P 2 Mother of Piet DG-P 5 Mother of Polly VHNK 129 Bello VHNK 128 Koala VHNK 111 Bally VHNK 33859 Pluis VHNK 51 Petit VHNK 70 Sita VR 338 Peggy Number of founders: 13 M/V Bitch Dog Bitch Bitch Year 1941 1945 1950 1954 1955 1966 Pup Rep Contribution Perc. % 1 1 468. 0 6. 0% 9 7 2907. 0 37. 1% 4 2 1116. 2 14. 2% 5 3 1322. 9 16. 9% 1 1 131. 2 1. 7% 1 1 7. 8 0. 1% 1 1 105. 2 1. 3% 9 3 1411. 9 18. 0% 6 2 115. 5 1. 5% 2 1 78. 4 1. 0% 10 1 159. 9 2. 0% 5 1 6. 2 0. 1% Current Population: 7838. 0 Sum 6. 0% 43. 1% 57. 3% 74. 2% 75. 9% 76. 0% 76. 1% 77. 4% 95. 4% 96. 9% 97. 9% 99. 9% 100. 0%

What is diversity (of the breed / population) Number of animals Population size / Founders Number of unique alleles Founder Genome Surviving (FGS) ▪ Estimated in “Number of animals” Spread of alleles / relatedness Founder Genome Equivalents (FGE) ▪ Estimated in “Number of animals” Inbreeding

Founders Wetterhoun Registration Nr Name Gender Year Pups Rep NHSB NR 34568 Juno Reu 1943 5 5 282. 5 30. 8% NHSB NR 40847 Mollie Teef 1942 3 3 167. 9 18. 3% 49. 1% NHSB NR 5 Sannie Reu 1945 4 2 132. 1 14. 4% 63. 5% NHSB NR 17 Sophie Teef 1943 1 1 90. 3 9. 8% 73. 4% NHSB G 0 275767 Fijkje Teef 1959 5 2 90. 2 9. 8% 83. 2% NHSB G 0 275897 Ferdau Teef 1956 5 1 82. 8 9. 0% 92. 2% NHSB G 0 154319 Mollix Reu 1946 2 1 36. 1 3. 9% 96. 2% NHSB NR 1 Reu 1942 2 1 18. 0 2. 0% 98. 1% Teef 1946 7 2 17. 0 917 1. 9% 100. 0% Jentje NHSB G 0 155121 Marina 8 Founders Totaal: Contri Perc. 100% Sum:

Founders Kooikerhondje Reg. Nr. Name DG-P 1 Mother of Biffie VHNK 21 Bobbie VHNK 132 Bennie (uit Friesland) VHNK 119 Tommie (uit Friesland) DG-P 2 Mother of Piet DG-P 5 Mother of Polly VHNK 129 Bello VHNK 128 Koala VHNK 111 Bally VHNK 33859 Pluis VHNK 51 Petit VHNK 70 Sita VR 338 Peggy Number of founders: 13 M/V Bitch Dog (M) Bitch Bitch Year 1941 1945 1950 1954 1955 1966 Pups Rep Contribution Perc. % 1 1 468. 0 6. 0% 9 7 2907. 0 37. 1% 4 2 1116. 2 14. 2% 5 3 1322. 9 16. 9% 1 1 131. 2 1. 7% 1 1 7. 8 0. 1% 1 1 105. 2 1. 3% 9 3 1411. 9 18. 0% 6 2 115. 5 1. 5% 2 1 78. 4 1. 0% 10 1 159. 9 2. 0% 5 1 6. 2 0. 1% Current Population: 7838. 0 Sum 6. 0% 43. 1% 57. 3% 74. 2% 75. 9% 76. 0% 76. 1% 77. 4% 95. 4% 96. 9% 97. 9% 99. 9% 100. 0%

FGS Founder Genome Surviving Number of (partial) founders that is still present in the current population FGS Scale: Number of animals ▪ Never higher than number of founders ▪ Never lower than 0. 5

De alleles. . 8 unique alleles in 4 animals F 1 F 2 F 3 F 4 || || 20. 000+ || => Founders: each gene unique => a. R ar a. B ab a. G ag a. Y ay !!!

Loss of diversity Founders: FGS 4 Loss over generations: 4 Loss of alleles: Founder Genome Survival 2

diversity: animals / alleles D 1 D 2 D 3 1 | | | 2 | | | 3 | | | 20. 000+ | | D 4 => population (4 animals) || => a 1 Ᾰ ᾶ || => β b 1 Б || => c 1 … => 3 unique alleles || || || FGS = 1. 5

Zoo populations Population: number of animals Founders: number of original unrelated wild caught animals FSG: Founder Genome Surviving (unique alleles) Species Cheetah Bonobo Red Panda Okapi Founders FGS FGE 1640 1590 366 11 200 103 52 60 550 279 50 21 269 165 24 18 Population

What is diversity (of the breed / population) Number of animals Population size / Founders Number of unique alleles Founder Genome Surviving (FGS) ▪ Estimated in “Number of animals” Spread of alleles / relatedness Founder Genome Equivalents (FGE) ▪ Estimated in “Number of animals” Inbreeding

Spread of alleles / relatedness (being family) Some alleles are overrepresented. . Some are underrepresented: Gene-frequenties. . Next: an example. .

Loss of diversity Founders: Loss over the generations: FGS FGE 4 4 4 2. 5 2 1. 3 Loss of alleles: Founder Genome Survival Spread of alleles: Genetic diversity or: Founder Genome Equivalents

Overrepresented (dominant) ancestors: Wetterhoun Name Boris Duke Alwin fen de Alde Slus Adrie fen ’t Marlân Berend fen de Otterhounen Abe fan de Snitser Zwik Wanda Elske Age fan ’e Leijensigge Akke van de Wero Beitske fan Mid Fryslân Gender Reu Reu Teef Teef Reu Teef Year 1971 1950 1962 1944 1956 1959 1944 1970 1961 1968 1954 1966 Halbart fan State Bearestein Reu 1979 Warmolt v. Wiejanka Brunbeant fan it Broeksteriziem Anoeska v. Wiejanka Reu Teef 1984 1967 1979 Father Mother Alwin fen de Alde Slus Wanda Sannie Adrie fen ’t Marlân Boate Elske Juno Mollie Duke Akke van de Wero Berend fen de Otterhounen Aukje fan ’t Wielenswal Juno Sophie Age fan ’e Leijensigge Bouck Remco fen de Otterhounen Ferdau Bear fan ’t Wielenswal Beitske fan Mid Fryslân Wibo fen ’t Wetterlân Bontje Abe fan de Snitser Formke Wiard fan de Brun Frodina fan State Goaijngeamieden Bearestein Elger from the Dogstable Froukje v. Wiejanka Zeus Nienkega Boris Doutsen fan’t Oerset Pups 197 27 37 14 19 62 19 35 16 25 12 23 Rep 15 5 4 5 6 2 4 4 3 4 Contr. 325. 4 35. 5% 238. 5 26. 0% 236. 2 25. 8% 210. 2 22. 9% 196. 7 21. 5% 193. 0 21. 0% 180. 6 19. 7% 176. 5 19. 2% 165. 7 18. 1% 161. 5 17. 6% 144. 2 15. 7% 127. 4 13. 9% 31 5 125. 5 9 38 22 4 5 3 124. 8 123. 0 122. 9 13. 7% 13. 6% 13. 4%

Overrepresented (dominant) ancestors: Kooikerhondje Registration Nr. Name Gender Year Father Mother Pups Rep Contr. VR 1 Nico Reu 1954 Cedric v Walhalla Kiddy 40 VHNK 7660 Kiddy Teef 1948 Robert v Walhalla Tim 5 Carlieneke v Walhalla 6 VHNK 10844 Cedric v Walhalla Reu 1953 Bally VHNK 27761 Nestor Reu 1954 Cedric v Walhalla Kiddy 62 VR 325 Anton v. Berkahoeve Reu 1970 Roderick v. d. Borchvree Judy 56 VR 31 Tobias Reu 1963 Nico Noortje v. d. Borchvree 43 VR 120 Bijntje Teef 1955 Piko Keetje 21 BYL. G-1 -793249 Quacatossy’s Hiawatha Reu 1975 Frans Bobby VHNK 3804 Margrietje v. Walhalla Teef 1942 Bennie (uit Friesland) VHNK 10838 Carlieneke v Walhalla Teef 1943 Bobbie Quacatossy’s Donderstormpje Tommie (stammoeder) uit Friesland Margrietje v. Walhalla VHNK 10834 Robert v Walhalla Reu 1944 Bobbie Margrietje v. Walhalla VHNK 14220 Aramis Reu 1949 Janus Kooiker Flapje VHNK 10836 Tim Teef 1947 Bobbie Tommie Ii v. Walhalla VR 26 Olivier v. d. Borchvree Reu 1962 Nico Bijntje BYL. G-0 -736727 Arjan Frieso v. Kooikersgraaf Reu 1974 Friso v. d. Csashjahoeve VHNK 3806 Tommie Ii v. Walhalla Teef 1942 Bennie (uit Friesland) VR 63 Roderick v. d. Borchvree Reu 1965 Tobias VR 512 Quacatossy’s Anouschjka Juliette Teef 1971 Wander VR 4 Bram Reu 1957 Nestor Quacatossy’s Anouschjka Juliette Tommie (stammoeder) uit Friesland Bijntje Vrouwe Astrid v. Neerlands Bloed Diana v. d. Roem v Boekel BYL. G-0 -966788 Hein Reu 1977 Nicky Judith 169 4 6 5 8 2296. 1 29% 4 2226. 3 29% 3 2172. 1 28% 12 1669. 8 21% 86% 58% 107% 13 1611. 8 21% 10 1557. 9 20% 128% 4 1409. 8 18% 10 1275. 2 16% 166% 3 1266. 3 16% 2 1204. 0 15% 148% 183% 199% 214% 2 1120. 7 14% 6 1113. 7 14% 229% 257% 29 1 1113. 2 14% 9 1104. 1 14% 73 14 1021. 1 13% 285% 2 2 966. 1 12% 3 956. 0 12% 17 1 23 14 29 2 891. 6 11% 7 847. 4 11% 131 17 838. 0 11% 243% 271% 297% 309% 321% 332% 342%

Relatedness vs. Genetic diversity

FGE: a numeric example

Loss of diversity Founders: Loss over generations: FGS FGE 4 4 4 2. 5 2 1. 3 Loss of alleles: Founder Genome Survival Spread of alleles: Genetic diversity or Founder Genome Equivalents

Loss of diversity This is still ongoing!! FGE: founder genome equivalents Is best predictor

Dierentuin populaties FGE: founder genome equivalents: How much diversity (or how little relatedness) Best predictor of inbreeding! Species Cheetah Bonobo Red Panda Okapi Population 1640 200 550 269 Founders 1590 103 279 165 FGS 366 52 50 24 FGE 60 21 18 11

The main message By overuse of few animals: specific genes become overrepresented Genes of dominant ancestors are present in all animals Making all current animals family to each other When all animals are family (highly related) ▪ Each mating causes inbreeding ▪ Inbreeding has become inevitable

What is diversity (of the breed / population) Number of animals Population size / Founders Number of unique alleles Founder Genome Surviving (FGS) Spread of alleles / relatedness Founder Genome Equivalents (FGE) Inbreeding Per individual On population level – depend on relatedness (and thus diversity)

Inbreeding per individual: what is that? 1: a||a 2: b||b 3: c||c 4: d||d 5 : d||d . . : d|| 20. 000+ | | => a 1 Ᾰ ᾶ ἀ a 2 => β b 1 Б B 2 => c 1 … … 25 => more often the same allele !!!

So. . What about inbreeding? Inbreeding is the chance of having the same Allele on a loci. . Value between: 0 and 100% A simple test in inbreeding You will not have to calculate. . Just know: Brother x sister mating: 25%

Inbreeding calculations & Generations In this slide [ F ] is the same Females are unrelated halfbrother / halfsister mating Inbreeding: female X ? ? ? male

Inbreeding calculations & Generations In this slide [ F ] is the same male Inbreeding: female X parents: halfbrother / halfsister : Inbreeding coefficient: 12. 5 % (brother x sister => 25% )

Inbreeding calculations & Generations In this slide [ F ] is the same male Inbreeding: male Y higher or lower than X? (of previous slide)

Inbreeding calculations & Generations In deze slide is [F] hetzelf de manne tje. Inbreeding: female Z ?

Inbreeding calculations: ALL generations 1 2 3 4 5 6 7 8 9 10 11 12 … … 20 2 4 8 16 32 64 128 256 512 1024 2048 4094 … … 1. 000 (a million)

Founders Wetterhoun Registration Nr Name Gender Year Pups Rep NHSB NR 34568 Juno Reu 1943 5 5 282. 5 30. 8% NHSB NR 40847 Mollie Teef 1942 3 3 167. 9 18. 3% 49. 1% NHSB NR 5 Sannie Reu 1945 4 2 132. 1 14. 4% 63. 5% NHSB NR 17 Sophie Teef 1943 1 1 90. 3 9. 8% 73. 4% NHSB G 0 275767 Fijkje Teef 1959 5 2 90. 2 9. 8% 83. 2% NHSB G 0 275897 Ferdau Teef 1956 5 1 82. 8 9. 0% 92. 2% NHSB G 0 154319 Mollix Reu 1946 2 1 36. 1 3. 9% 96. 2% NHSB NR 1 Reu 1942 2 1 18. 0 2. 0% 98. 1% Teef 1946 7 2 17. 0 917 1. 9% 100. 0% Jentje NHSB G 0 155121 Marina 8 Founders Totaal: Contri Perc. 100% Sum:

Overrepresented (dominant) ancestors: Wetterhoun Name Boris Duke Alwin fen de Alde Slus Adrie fen ’t Marlân Berend fen de Otterhounen Abe fan de Snitser Zwik Wanda Elske Age fan ’e Leijensigge Akke van de Wero Beitske fan Mid Fryslân Gender Reu Reu Teef Teef Reu Teef Year 1971 1950 1962 1944 1956 1959 1944 1970 1961 1968 1954 1966 Halbart fan State Bearestein Reu 1979 Warmolt v. Wiejanka Brunbeant fan it Broeksteriziem Anoeska v. Wiejanka Reu Teef 1984 1967 1979 Father Mother Alwin fen de Alde Slus Wanda Sannie Adrie fen ’t Marlân Boate Elske Juno Mollie Duke Akke van de Wero Berend fen de Otterhounen Aukje fan ’t Wielenswal Juno Sophie Age fan ’e Leijensigge Bouck Remco fen de Otterhounen Ferdau Bear fan ’t Wielenswal Beitske fan Mid Fryslân Wibo fen ’t Wetterlân Bontje Abe fan de Snitser Formke Wiard fan de Brun Frodina fan State Goaijngeamieden Bearestein Elger from the Dogstable Froukje v. Wiejanka Zeus Nienkega Boris Doutsen fan’t Oerset Pups 197 27 37 14 19 62 19 35 16 25 12 23 Rep 15 5 4 5 6 2 4 4 3 4 Contr. 325. 4 35. 5% 238. 5 26. 0% 236. 2 25. 8% 210. 2 22. 9% 196. 7 21. 5% 193. 0 21. 0% 180. 6 19. 7% 176. 5 19. 2% 165. 7 18. 1% 161. 5 17. 6% 144. 2 15. 7% 127. 4 13. 9% 31 5 125. 5 9 38 22 4 5 3 124. 8 123. 0 122. 9 13. 7% 13. 6% 13. 4%

5 Statements Most software used by breeders work with 10 generations 1) For inbreeding calculations 10 generations is enough. True? ? Yes / No

Diversity & Inbreeding What is the relation between: diversity and inbreeding? !? ! Without diversity all animals are related (family) Diversity = 1 – relatedness (average!!) Each mating is now: inbreeding thus: (higher) chance that 2 genes on one locus are the same allele

Diversity & Inbreeding follows loss of diversity It is NOT the cause! Example: one new founder: ▪ next generation: Inbreeding is 0%. . ▪ and than? ? Also: inbreeding is genetic but not heritable ▪ An inbred animal can be healthy ▪ But the chance is really low

5 Statements The most practised measure taken is to avoid inbreeding of a litter (by disallowing parent offspring matings and check inbreeding of a litter before a mating 3) By avoiding inbreeding, we keep the diversity of the breed. True? Yes / No

Diversity & Inbreeding Diversity decreases Ø Relatedness increases Ø Inbreeding increases (inevitably) Ø Animals become affected more often!!

Breed specific diseases Bernese Mountain Dog • • • “ 50% dies of cancer around age of 5” Other research Berner Sennenhund shows 45. 7% High incidence as well: • Irish water spaniel (51%), • Flat-coated retriever (50. 3%), • Vizsla (rough-haired) 46, 7% • Uninvestigated breeds? !? ! • Polygenetic!. . also • • Epilepsy en Polymyositis (Kooikerhondje) De Wetterhoun Severe Combined Immune Deficiency (SCID) Monogenetic (fortunately there is a solid DNA test!!) Other breeds? ! • • • Polygenetic Monogenetic Many many breed specific genetic diseases are known

Genetic diseases. . . (700+) Acepromazine sensitivity; Achalasia; Achondrogenesis; Achondroplasia; Achromatopsia type 3; Acinar atrophy; Acne vulgaris; Acral mutilation; Addison’s disease; Adrenal hyperplasia; Afibrinogenaemia; Aggressive temperament; Alabama rot; Alexander disease; Alopecia X; Alport syndrome; Amblyopia; Amyloidosis; Anaemia; Anemia. Hunter syndrome; Hurler-Scheie syndrome; Hyaluronan accumulation; Hydroxyglutaric acidurea (1 -2 -HGA); Hydrocephalus and hypertrichosis; Hydronephrosis; Hyperadrenocorticism; Hypercalcemia; Hyperlipidaemia; Hyperlipoproteinaemia; Hyperparathyroidism and renal cortical Hypoplasia (juvenile); Hyperparathyroidism- neoplasia; Hypertonic myopathies (Scotty Cramp); Hypertrophic cardiomyopathy; Hypertrophic neuropathy; Hypertrophic osteodystrophy/ hydroxylapetite deposition disease; Hyperuricosuria; Hypoadrenocorticism; Hypochondrodysplasia; Hypochondroplastic dwarfism; Hypofibrinogenemia; Hypofibrinogenaemia; Hypomyelinating neuropathy; Hypomyelination; Hypospadias; Hypothyroidism with hyperlipoproteinaemia; Hypothyroidism with hypomyelination; Ichthyosis; Idiopathic haemorrhagic pericardial effusion; Idiopathic polyneuropathy; Idiopathic thrombocytopenic purpura (ITP); Ig. A deficiency – inflammatory enteropathy; Imerslund-Grasbeck syndrome; Immune mediated thrombocytopenia; Immunodeficiency syndrome; Immunodeficient dwarfism; Immunoproliferative enteropathy; Incomplete ossification of humeral condyle; Infertility; Inflammatory bowel disease; Intradural haemorrhage; Intradural vasculitis; Interdog dominance aggression; Intervertebral disc calcification; Intervertebral disc herniation; Intraocular xanthogranuloma; Intrinsic platelet function defect; Iris cysts; Ivermectin sensitivity; Juvenile polyarteritis; Juvenile myopathy; Juvenile nephropathy; Juvenile onset polyarthritis; Juvenile renal disease; Kartagener’s syndrome; Keratoconjunctivitis sicca; Keratinisation defect; Kidney stones; Knee problems; Knobbed acrosome defect; Knock knees; Krabbe disease; Lafora's disease; Laryngeal paralysis-polyneuropathy; Leber congenital amaurosis; Legg-Calve Perthe disease; Leishmania susceptibility; Lens luxation; Lentiginosis profusa; Lethal acrodermatitis; Lethal astrocytosis; Leukodystrophy; Leukoencephalo-myelopathy; Leukopenia; Lipid storage disease (Wolman disease); Lissencephaly; Lobster Claw Deformity; Longevity; Lower motor neuron disease; Low Glutathione-S-Transferase; Lumbosacral osteochondrosis; Lung lobe torsion; Lymphocytic thyroiditis; Lymphoedema; Lymphosarcoma; Malignant histiocytosis; Malignant hyperthermia; Masticatory muscle myositis; Medullary thyroid carcinoma; Megaoesophagus; Meningoencephalitis; Metaphyseal osteopathy; Microphthalmia and anterior segment defects; Microphthalmia with coloboma; Microphthalmia with multiple ocular defects; Mitochondrial encephalomyopathy; Mitochondrial myopathy; Mitral (left atrio-ventricular) valve defects; Mitral (left atrio-ventricular) valve dysplasia; Mitral stenosis; Motor neuron abiotrophy; Mucinosis; Mucopolysaccharidosis I (Hurler-Scheie syndrome); Mucopolysaccharidosis II (Hunter syndrome); Mucopolysaccharidosis IIIa (Sanfilippo syndrome); Mucopolysaccharidosis IIIb (Sanfilippo syndrome); Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome); Mucopolysaccharidosis VII (Sly syndrome); Multicentric lymphoma; Multifocal retinal dysplasia (no skeletal deformities); Multifocal retinal dysplasia with skeletal abnormalities (Oculo-skeletal dysplasia); Multifocal retinopathy; Multiple epiphyseal dysplasia; Multiple ocular defects; Muscular dystrophy; Muscle hypertonicity; Musladin-Leuke Syndrome; Myasthenia gravis; Myoclonus epilepsy; Myopathy and neuropathy; Myopia; Myotonic dystrophy; Myotonic myopathy; Narcolepsy; Nasal dermatitis; Nasal parakeratosis; Necrosis of femoral head (Legg-Calve-Perthe disease); Necrotizing encephalitis; Necrotizing meningoencephalomyelitis; Nemaline rod myopathy; Neonatal encephalopathy with seizures; Neoplasia – glioma; Neoplasia – haemangioma & haemangiosarcoma; Neoplasia - histiocytosis; Neoplasia – mammary carcinoma; Neoplasia – mast cell tumour; Neoplasia – oral melanoma; Neoplasia – osteosarcoma; Neoplasia – soft tissue sarcoma; Neoplasia, various; Nephropathy (juvenile); Nervousness; Neural Tube Defect; Neuroaxonal dystrophy (NAD); Neurodegeneration; Neurogenic muscular atrophy; Neuronal abiotrophy; Neuronal ceroid lipofuscinosis; Neuronal vacuolation; Neutrophil defect; Niemann-Pick disease Type A/B; Niemann-Pick disease Type C; Non-Hodgkin's lymphoma; Nonspherocytic hemolysis; Ocular dermoid cysts; Ocular melanosis; Oculo-skeletal dysplasia, drd 1; Oculo-skeletal dysplasia, drd 2; Oculo-skeletalheamatological syndrome; Oligodendroglial dystrophy; Oligodontia; Onychodystrophy; Optic nerve hypoplasia; Osmotic fragility; Osteoarthrosis; Osteochondrodysplasia; Osteochondromatosis; Osteochondrosis dissecans, shoulder & stifle joints; Osteochondrosis of lateral trochlear ridge; Osteogenesis imperfecta; Otitis externa; Overshot jaw; Oxalate nephropathy; Palmoplantar hyperkeratosis; Pancreatic acinar atrophy; Pancreatitis; Panniculitis; Pannus; Paroxysmal dystonic choreoathetosis; Paroxysmal seizures; Patent ductus arteriosus; Patellar luxation; Pectus excavatum; Pectinate ligament dyplasia; Pemphigus foliaceus; Pericardial mesothelioma; Peripheral (femoral) artery occlusive disease; Peripheral neuropathy; Perivasculitis; Persistent hyaloid remnants; Persistent hyperplastic primary vitreous (PHPV)/Persistent hyperplastica tunica vasculosa lentis (PHTVL); Persistent hyperplastic tunic vasculosa lentis (PHTVL); Persistent Mullerian duct syndrome (PMDS); Persistent pupillary membranes; Persistent right aortic arch; Persistent scratching; Pharmacogenetic abnormalities; Pigmentary glaucoma; Pituitary dependent hyperadrenocorticism; Pituitary dwarfism (combined pituitary hormone deficiency); Platelet mediated bleeding disorder (Scott's syndrome); Platelet storage pool defect (with cyclic neutropenia); Pneumocystis pneumonia; Polioencephalomyelopathy; Polycystic kidney and liver disease; Polycystic kidney disease; Polydactyly and skeletal and soft tissue abnormalities; Polydactyly and skeletal malformations; Polyglucosan body disease; Polyneuropathy; Polyradiculoneuritis; Portosystemic shunt; Primary familial hyperphosphatasemia; Primary glaucoma; Primary hyperoxaluria type 1; Primary hypertension; Primary open angle glaucoma; Primary orthostatic tremor; Primary sensory neuropathy; Progressive axonopathy; Progressive hereditary nephritis; Progressive paralysis and dementia (Alexander Disease); Progressive Retinal Atrophy – early retinal degeneration (erd); Progressive Retinal Atrophy of late onset; Progressive Retinal Atrophy – photoreceptor dysplasia (pd); Progressive Retinal Atrophy- probably as rod-cone dystrophy type 1 (rcd 1); Progressive Retinal Atrophy – progressive rod cone degeneration (prcd); Progressive Retinal Atrophy – rod-cone dystrophy type 2 (rcd 2); Progressive Retinal Atrophy – rod-cone dystrophy type 3 (rcd 3); Progressive Retinal Atrophy – X-linked progressive retinal atrophy; Progressive Retinal Atrophy (retinal pigment epithelium dystrophy); Progressive Rod Cone Degeneration; Protein losing enteropathy (PLE); Protein losing nephropathy (PLN); Pseudoachondroplasia; Psychomotor retardation; Pulmonary fibrosis; Pulmonary hypertension; Pulmonary Oedema; Pulmonic stenosis; Pyoderma (skin infections); Pyruvate kinase deficiency; Quadriplegia; Rage Syndrome; Renal amyloidosis; Renal calculi; Renal cystadenocarcinoma and nodular dermatofibrosis; Renal dysplasia; Renal vasculopathy; Respiratory distress syndrome; Retinal dysplasia (multifocal, mrd); Retinal dysplasia/degeneration - ceroid lipofuscinosis; Retinal Ganglion cell distribution; Retinal pigment epithelium dystrophy; Rhinitis; Sacral osteochondrosis; Sandhoff disease; Sanfilippo syndrome; Sarcoma; Schisis; Scott's syndrome; Sebaceous adenitis; Sebacious gland hyperplasia; Seborrhoea; See-saw nystagmus; Seizures: malonic acidurea; Selective intestinal cobalamin malabsorption; Sensorial deafness; Sensorineural deafness; Sensory axonopathy; Severe combined immunodeficiency (SCID); Shaking pup; Shar Pei Fever; Sick sinus syndrome; Siezures (partial); Skin and hair abnormalities; Sly syndrome; Sodium thiopentane sensitivity; Solid intraocular xanthogranuloma; Spectrin Deficiency; Spherocytosis; Spina bifida; Spinal cerebellar degeneration; Spinal muscular atrophy; Spondyloarthrosis; Spondylo-epithelial dysplasia; Spondylolithesis; Spontaneous chronic corneal epithelial defects (SCCED); Spontaneous hypertension; Sry –ve sex reversal; Stenosis of the bundle of His; Stiff Skin Syndrome; Stomatocytosis with chondrodysplasia; Stomatocytosis with hypertrophic gastritis; Subacute necrotizing encephalopathy; Subaortic stenosis; Sudden Acquired Retinal Degeneration Syndrome; Sudden death syndrome; Superficial stromal keratitis; Symmetrical Lupoid Onychodystrophy; Syringomelia; Syringohydromelia; Systemic lupus erythematosis; Tail chasing; Tapetal degeneration; Taurine deficiency; Tay-Sachs disease; T-cell non-Hodgkin's lymphoma; Telangiectasia; Tetralogy of Falot; Thiopurine-SMethyltransferase deficiency; Thrombocytopenia; Thrombopathy: delta storage pool defect; Thyroiditis; Tied tongue; Tracheal collapse; Trapped neutrophil syndrome; Tremor syndrome: central axonopathy; Tricuspid (right atrioventricular) valve dysplasia; Tubular transport dysfunction “Fanconi’s syndrome”; Type 1 von Willebrand disease; Type 2 von Willebrand disease; Type 3 von Willebrand disease; Urate urolithiasis; Urinary incontinence; Uroliths (cystine); Uroliths (struvite, oxalate, other); Uveodermatological syndrome; Vasculitis; Ventricular arrhythmia; Ventricular septal defect; Vitiligo; Vitreous degeneration; Vogt-Koyanagi-Harada syndrome; White matter spongy degeneration; Wobbler syndrome; Xanthinuria; X-linked myopathy: muscular dystrophy; X-Linked Progressive Retinal Atrophy XLPRA 1; X-linked Progressive Retinal Atrophy XLPRA 2; X-linked severe combined immunodeficiency; Zinc responsive dermatosis; ; Aniridia; Ankyloglossia; Anury (absence of tail); Aortic aneurysm; Aortic stenosis; Arnold-Chiari malformation; Arteritis; Aseptic meningitis; Asthma; Ataxia and myelopathy; Atherosclerosis; Atopic dermatitis; Atrial septal defect; Atrioventricular heart block; Attention deficit disorder; Autoimmune haemolytic anaemia; Autoimmune thyroiditis; Axonal neuropathy; Basset thrombopathia; B-cell non-Hodgkin's lymphoma; Beagle pain syndrome; Beta adrenoreceptor insensitivity; Bilateral sensorial deafness; Birt-Hogg-Dube syndrome; Black hair follicular dysplasia; Black skin disease; Blindness with ocular developmental anomalies; Bloat; Blue-eye; Bob-tail trait; Brachycephalic airway syndrome; Brachycephaly; Brachygnathia; Brachyury; Bradyarrhythmia; Brittle bone disease; Calcinosis circumscripta; Calcium excess mediated bone disease; Cancer; Canine adenovirus type 1 (CAV 1) sensitivity; Canine hereditary multi-systems atrophy (CHMSA); Canine leukocyte adhesion deficiency (CLAD); Canine motor neurone disease; Cardiac arrhythmias; Cardiac valvular defects; Cardiomyopathy; Caroli's disease; Carpus subluxation; Catalase deficiency; Cataract; Central core myopathy; Centronuclear myopathy (cnm); Cerebellar and cerebral cortical degeneration; Cerebellar ataxia - extrapyramidal abiotrophy; Cerebellar cortical abiotrophies; Cerebellar degeneration (immune mediated); Ceroid lipofuscinosis type 2; Ceroid lipofuscinosis (ceroidal retinal degeneration); Cervical disc prolapse; Charcot-Marie-Tooth disease; Cherry Eye; Chondrodysplasia; Chondrodystrophia; Choroidal hypoplasia; Chronic pancreatitis; Chronic superficial keratitis of the cornea; Chronic valvular disease; Chylothorax; Ciliary dyskinesia (Kartagener’s syndrome); Cleft palate; Clotting disorder; Cobalamin malabsorption; Coeliac disease; Collie eye anomaly (CEA); Colour dilution alopecia (CDA); Cone-rod dystrophy; Congenital adrenal hyperplasia syndrome; Comedones; Common variable immunodeficiency; Complement (C 3) deficiency; Cone degeneration (cd); Congenital sensorineural deafness with microphthalmia; Congenital Stationary Night Blindness (CSNB); Conotruncal defect; Conjunctivitis; Coonhound paralysis; Copper associated liver disease; Copper toxicosis; Cori disease; Corneal dystrophy; Corneal endothelial dystrophy; Corneal oedema; Corneal ulcers; Cornification and multiple congenital defects; Cornification defect; Cornifying epithelioma (Keratocanthoma); Cranial cruciate ligament rupture; Cranio-mandibular osteopathy; Cranioschisis; Cricopharyngeal achalasia; Cricopharangeal dysfunction; Cryptorchidism; Cushing syndrome (congenital); Cutaneous asthenia (Ehlers Danlos syndrome); Cutaneous lupus erythematosis; Cutaneous vasculopathy; Cyclic hematopoiesis; Cyclic neutropenia; Cysteine and urate uroliths; Cystic bone lesions; Cystine and urate uroliths; Cystinuria; Dancing Doberman disease; Degenerative encephalomyelopathy; Degenerative myelopathy; Demodicosis; Demyelination; Dermatitis; Dermatofibrosis (nodular); Dermatomyositis; Dewclaw; D-glyceric acidurea; D-glycericacidaemia; D-glycerate kinase deficiency; Diabetes mellitus; Diabetes mellitus (gestational); Diabetes insipidus; Dilated cardiomyopathy; Displaced canine teeth; Distal myopathy; Distal polyneuropathy; Distichiasis; Doberman hepatitis; Double Muscling; Dry eye; Dwarfism: pseudoachondroplastic dysplasia; Dyskinesia in pups; Dysphagia; Dysraphic spine; Dystocia; Ear Inflammation; Ectodermal dysplasia; Ectopia lentis; Ectopic ureters; Ectrodactyly; Ehlers Danlos syndrome; Elbow deformity; Elbow dysplasia; Elbow incongruity; Elliptocytosis; Emphysema with bronchial hypoplasia; Encephalitis; Encephalomyelopathy; Entropion; Epidermolysis bullosa; Epilepsy; Essential hypertension; Everted membrane nictitans; Exercise induced collapse; Exocrine pancreatic insufficiency; Factor I (Fibrinogen) deficiency; Factor II (Prothrombin) deficiency; Factor VII (Proconvertin) deficiency; Factor X (Stuart-Prower Factor) deficiency; Factor XI (Plasma Thromboplastin Antecedent) deficiency; Factor XII (Hageman Factor) deficiency; Familial focal seizures; Familial nephropathy; Familial renal disease; Fanconi syndrome; Fibrodysplasia Ossificans; Fibrinoid Leukodystrophy; Fibrosarcoma; Forbes disease; Fractures of humeral condyle; Fucosidosis (alpha); Galactocerebrosidosis; Galactosialidosis; Gastric carcinoma; Gastric dilatation/ volvulus; Gastropathy; Gaucher’s disease I; Generalised tremor; Giant axonal neuropathy; Gingival hypertrophy; Glanzmann’s-type I thrombasthenia; Glaucoma - pigmentary; Glaucoma - secondary; Glaucoma with ciliary body cysts; Globoid cell leukodystrophy; Glomerulonephropathy; Glomerulonephritis; Glucosuria; Glutathione-S-Transferase deficiency; Gluten sensitive enteropathy; Glycogen storage disease Ia (von Gierke disease); Glycogen storage disease II (Pompe disease); Glycogen storage disease type IIIa; Glycogen storage disease IV; Glycogen storage disease VII, (Phosphofructokinase deficiency); GM 1 gangliosidosis; GM 2 gangliosidosis (type AB) (Tay Sachs disease, AB variant); GM 2 gangliosidosis (type B) (Sandhoff disease); Goniodysgenesis; GSTT 1 deficiency; Grey matter spongy degeneration; Guillaine Barre syndrome; Haemophilia A; Haemophilia B; Hair loss; Hairless, defective teeth; Hairless, small litter size; Halothane sensitivity; Hemeralopia; Hemimelia; Hemivertebrae; Hemophagocytic histiocytic sarcoma; Hemophilia; Hepatitis (chronic active); Hepatocerebellar degeneration; Hepatoportal microvascular dysplasia; Hereditary ataxia; Hereditary myelopathy; Hereditary myopathy; Hereditary necrotizing myelopathy; Hereditary nephritis; Hereditary polyneuropathy; Hereditary spinal muscular atrophy (“Canine motor neurone disease”); Hereditary ventricular tachycardia; Hexosaminidase B deficiency; High K erythrocytes; Hindlimb lameness; Hip dysplasia; Histiocytic sarcoma; Histiocytic ulcerative colitis; Horner’s syndrome;

Inbred is not ‘pure-bred’ 20. 000 loci (genes) in the dog Half of each parent Just 100 to 1000 loci (genes) determine the breed Only 5 – 10 loci are most influential 19. 000 genes (loci) are NOT influential. . Each mammal has 5 recessive genetic diseases Inbreeding ‘elevates’ these diseases

5 Statements Many test’s for diseases are required before breeding is allowd 2) Diseases within a breed can be avoided by selecting against the affected animals. True? Yes / No

Selection against diseases. . Berner Sennenhund 80 s: Clinical Hip Dysplasia 90 s: Elbow Dysplasia Now: High incidence of cancer Kooikerhondje 80 s: Von Willebrand (v. WF) Now: Polymyocitis

Inbreeding depression There is another disadvantage: Sensitive to the environment Low immune response Less fitness Litter sizes milk-production fertility Longevity This differs per population

Inbred strains 100% Homozygous (completely inbred) 20+ rat-strains (with ‘variations’) 50+ mouse strains(with‘variations’) 2 cavy strains (Guiney Pig)

Inbred strains

Breeding for diversity Diversity is highest when relatedness (mean kinship) is lowest Diversity ‘prevents’ inbreeding an genetic diseases ▪ Also: Inbreeding depression ▪ p. s. an exception is healthy inbred strains. . Without diversity no selection possible!!

5 a 10 minute break After: How about diversity (and thus inbreeding) in our dog breeds?

What is Diversity? FGE (in %: genetic Diversity) Formula = 1 / (2 * mean kinship) Calculated via kinship Founder Genome Equivalents FGS: (in %: Allel Diversity) Formula = ½ * # Alleles Calculated via genedrop Founder Genome Survival

On the background… Dog populations are fundamentally different from ‘natural populations’ or livestock populations Within population genetics I never found one rule that is applicable to all populations in need of conservation (endangered species or rare breeds)

Dierentuin populaties FGE: founder genome equivalents: How much diversity (or how little relatedness) Best predictor of inbreeding! Species Cheetah Bonobo Red Panda Okapi Population 1640 200 550 269 Founders 1590 103 279 165 FGS 366 52 50 24 FGE 60 21 18 11

Dog breeds FGE: founder genome equivalents: How much diversity (or how little relatedness) Best predictor of inbreeding! Breed Lancashire Heeler Icelandic Sheepdog Toller Stabyhoun Wetterhoun Saarloos Wolfdog Population Founders 3400 3000 25. 000+ 7000 1000 700 FGS FGE 5 24 9 30 22 2 2. 5 2. 4 1. 9 1. 5 1. 3 1? ?

Inbred strains

Icelandic Sheepdog: example

Population Size Icelandic Sheepdog

Founders & Diversity Scale: number of animals

Years 2017 2015 2013 2011 2009 2007 2005 2003 2001 1999 1997 1995 1993 1991 1989 1987 1985 1983 1981 1979 1977 1975 1973 1971 1969 Inbreeding 1967 1965 1963 1961 1959 1957 1955 1953 1951 1949 1947 1945 1943 1941 Average Kinship / Inbreeding Scale: Percentage Kinship 0, 4 0, 35 0, 3 0, 25 0, 2 0, 15 0, 1 0, 05 0

Conclusions for: Icelandic Sheepdog What you look at determines your conclusion: Number of dogs increases => good! Inbreeding (rate of -) is not dramatic => neutral Number of unique alleles show strong decrease => bad!! Population-size does not tell us much Also (rate of) inbreeding not predictive ▪ Side note: nor is effective population size

Cluster-analyse: what happened?

Conclusions on loss of diversity Loss goes unnoticed due to 2 reasons: 1. Small number of ‘best’ males dominate ▪ This is a continues process ▪ On a pedigree you can NOT see how much animals are truly related 2. Unrelated animals are NOT noticed ▪ Their loss keeps on being undetected ▪ On a pedigree you can NOT see which animals are truly UNrelated

Warning Actually almost nothing done to keep diversity within dog breeds!!! Sometimes you see max of 3 litters per dog or bitch ▪ This is possibly just a “drop in the ocean” ▪ True loss happens over generations Inbreeding as a tool does NOT avoid inbreeding

Current measures for preservation of diversity Inbreeding limitations: No grandparent – grandchild No brother – sister, etc. . Restriction on litters: Maximum 3 - 4 - 5 litters

Current measures for preservation of diversity Inbreeding limitations: Has NO influence on preservation of diversity Has NO influence on inbreeding in the future Example: We find an unrelated dog (founder)

Overrepresented (dominant) ancestors Registration Nr. Name Gender Year Father Mother Pups Rep Contr. VR 1 Nico Reu 1954 Cedric v Walhalla Kiddy 40 VHNK 7660 Kiddy Teef 1948 Robert v Walhalla Tim 5 Carlieneke v Walhalla 6 VHNK 10844 Cedric v Walhalla Reu 1953 Bally VHNK 27761 Nestor Reu 1954 Cedric v Walhalla Kiddy 62 VR 325 Anton v. Berkahoeve Reu 1970 Roderick v. d. Borchvree Judy 56 VR 31 Tobias Reu 1963 Nico Noortje v. d. Borchvree 43 VR 120 Bijntje Teef 1955 Piko Keetje 21 BYL. G-1 -793249 Quacatossy’s Hiawatha Reu 1975 Frans Bobby VHNK 3804 Margrietje v. Walhalla Teef 1942 Bennie (uit Friesland) VHNK 10838 Carlieneke v Walhalla Teef 1943 Bobbie Quacatossy’s Donderstormpje Tommie (stammoeder) uit Friesland Margrietje v. Walhalla VHNK 10834 Robert v Walhalla Reu 1944 Bobbie Margrietje v. Walhalla VHNK 14220 Aramis Reu 1949 Janus Kooiker Flapje VHNK 10836 Tim Teef 1947 Bobbie Tommie Ii v. Walhalla VR 26 Olivier v. d. Borchvree Reu 1962 Nico Bijntje BYL. G-0 -736727 Arjan Frieso v. Kooikersgraaf Reu 1974 Friso v. d. Csashjahoeve VHNK 3806 Tommie Ii v. Walhalla Teef 1942 Bennie (uit Friesland) VR 63 Roderick v. d. Borchvree Reu 1965 Tobias VR 512 Quacatossy’s Anouschjka Juliette Teef 1971 Wander VR 4 Bram Reu 1957 Nestor Quacatossy’s Anouschjka Juliette Tommie (stammoeder) uit Friesland Bijntje Vrouwe Astrid v. Neerlands Bloed Diana v. d. Roem v Boekel BYL. G-0 -966788 Hein Reu 1977 Nicky Judith 169 4 6 5 8 2296. 1 29% 4 2226. 3 29% 3 2172. 1 28% 12 1669. 8 21% 86% 58% 107% 13 1611. 8 21% 10 1557. 9 20% 128% 4 1409. 8 18% 10 1275. 2 16% 166% 3 1266. 3 16% 2 1204. 0 15% 148% 183% 199% 214% 2 1120. 7 14% 6 1113. 7 14% 229% 257% 29 1 1113. 2 14% 9 1104. 1 14% 73 14 1021. 1 13% 285% 2 2 966. 1 12% 3 956. 0 12% 17 1 23 14 29 2 891. 6 11% 7 847. 4 11% 131 17 838. 0 11% 243% 271% 297% 309% 321% 332% 342%

Loss of diversity Founders: Loss over the generations: FGS FGE 4 4 4 2. 5 2 1. 3 Loss of alleles: Founder Genome Survival Spread of alleles: Genetic diversity or: Founder Genome Equivalents

Dog breeds FGE: founder genome equivalents: How much diversity (or how little relatedness) Best predictor of inbreeding! Breed Lancashire Heeler Icelandic Sheepdog Toller Stabyhoun Wetterhoun Saarloos Wolfdog Population Founders 3400 3000 25. 000+ 7000 1000 700 FGS FGE 5 24 9 30 22 2 2. 5 2. 4 1. 9 1. 5 1. 3 1? ?

What can we do? Loss happens unnoticed; 2 causes 1. Small number ‘best’ best dominate breeding 2. Unrelated animals are NOT detected This can be different. . .

Preserve Diversity 3 ways: Stimulate: Mean one time litters Kinship Crossbreeding / new founders (+ 1) promote your breed: more dogs

Stimulate: one time litters Use all dogs. . Possible? ? Stimulate Suppose “one time litters” each dog is used only one time. . Is there any selection? !

5 Statements 4) If you don’t select against the wrong traits (like cataract) these traits will be spread over the population True? Yes / No

Stimulate: one time litters Use as many different dogs as possible This is for both dogs and bitches Think about it: which tests are absolutely nessary? Testing might mean: selection Tell owners and veterinarians: stop castrating all dogs Proposal: ? ? Are there clinical cases of HD in the Curly Coated Retriever? Maybe no HD test for a first litter? No obligation to have been on show for first litter? What do you see as (in-)possibilities?

5 Statements Almost all breeds require X-ray for HD before being used in breeding 5) HD-testing is necessary or at least not harmful for a breed True? Yes / No

Preserve Diversity 3 ways: Stimulate: Mean one time litters Kinship Find the unrelated animals Crossbreeding / new founders (+ 1) promote your breed: more dogs

Selection: saving genetic diversity (within populations) Some animals have more unique alleles (diversity) than others This is calculated by “mean kinship” -> relatedness

Mean kinship (mk) … you can skip this slide … Average relatedness of one animal to all other animals of the population (including oneself): A B C D A 0. 6 0. 3 0. 1 0. 2 B 0. 3 0. 5 0. 2 C 0. 1 0. 2 0. 6 0. 1 D mk 0. 2 => 0. 3 0. 2 0. 1 0. 7 … Question ? !? !? !

Mean kinship per (living) animal example: Wetterhoun Registratie Nr NHSB 2727149 NHSB 2654390 NHSB 2654389 NHSB 2654388 NHSB 2683646 NHSB 2727153 NHSB 2727152 NHSB 2796760 NHSB 2727150 NHSB 2683645 NHSB 2798996 NHSB 2798997 NHSB 2837258 NHSB 2649162 NHSB 2727148 NHSB 2734552 NHSB 2727151 NHSB 2658030 NHSB 2837259 NHSB 2837260 NHSB 2837264 NHSB 2837262 NHSB 2837263 NHSB 2837261 NHSB 2807208 NHSB 2658028 NHSB 2683643 NHSB 2658032 NHSB 2658033 NHSB 2658029 NHSB 2658034 NHSB 2658027 NHSB 2683644 NHSB 2649163 Naam Doede v. d. eestroom Murron Joeke Caillou Yentel van jasmijndomein Oege v. d. eestroom Lolle v. d. eestroom Ids fan smahusum Tamme v. d. eestroom Boris van jasmijndomein Famke Fopke Brend fan 'e wetterkrite Gerben Reitze v. d. eestroom Wobbe-jascha fan 'e wetterkrite Gurbe v. d. eestroom Nelly Jeldert fan 'e wetterkrite Folmer fan 'e wetterkrite Marrit fan 'e wetterkrite Wiep fan 'e wetterkrite Frouke fan 'e wetterkrite Ygram fan 'e wetterkrite Akka Wette Bumbel van jasmijndomein Jenta Hasse Bijke Targa Lieuwe Banjer van jasmijndomein Wytze Geboren 10/11/2008 05/05/2007 07/12/2007 10/11/2008 24/05/2010 10/11/2008 07/12/2007 11/06/2010 26/04/2011 23/03/2007 10/11/2008 13/01/2009 10/11/2008 24/05/2007 26/04/2011 26/04/2011 26/08/2010 24/05/2007 07/12/2007 24/05/2007 24/05/2007 07/12/2007 23/03/2007 M/V M Nakomelingen 0 0 0 0 0 0 0 0 19 0 0 Mean Kinship 35 35 35 35 35 35 35 35 35

Inbreeding (COI) vs. Mean Kinship (mk) Like Inbreeding mk is between 0 and 1 or between 0% and 100% Though the basis of the calculations are similar, mean kinship behaves completely different. A comparison:

Saving diversity: 4 steps Example: • • Icelandic Sheepdog 15. 000+ 1956 Iceland – Scandinavia – NL, DE, FR USA • Should be as clean as possible

Mean kinship: Leonberger Where do we find diversity? KInship in the Leonberger per Country Other Norway Russia Sweden Australia Hungary Slovak Rep. Finland Switzerland New Zealand Canada Spain Austria Denmark Italy USA Poland Belgium Great Britain Czech Republic Netherlands Germany France 0 1000 2000 3000 4000 5000 6000 7000 8000

Preserve Diversity 3 ways: Stimulate: Mean one time litters Kinship Crossbreeding / new founders What to expect? How many are needed? Do you lose the type? (+ 1) promote your breed: more dogs

Examples Saarlooswolfhond Swiss white shepherd Siberian Husky How many crossbreds are needed? And what then? ? => Lecture on it’s own. . Podenco Portuguese Wetterhoun Labrador retriever Poodle “Frisian Dogs” Samoyed Nenet Laika

Cross-breeding alone is by far not enough.

Crossbreeding is no ‘pil’

Crossbreeding: how Many animals Having a lot of offspring

Dog breeds & breeding for diversity www. dogsglobal. com One-time litters Mean Kinship Keep FGE at same level Increase FGE towards FGS Crossbreeding or adding new founders => WHEN? ? Increase FGS Breed Lancashire Heeler Icelandic Sheepdog Toller Stabyhoun Wetterhoun Saarloos Wolfdog Population Founders 3400 3000 25. 000+ 7000 1000 700 FGS FGE 5 24 9 30 22 2 2. 5 2. 4 1. 9 1. 5 1. 3 1? ?

Summary Breeds lost dramatic amount of Diversity Caused by decades over use of few ‘best’ dogs Main cause of all genetic diseases and suffering This loss is still ongoing! Highest priority: stop this leak of diversity, by: Stimulation of one-time litters Mean Kinship Crossbreeding only useful when carried out smart First look for diversity within the breed “Type” cán be preserved as well

www. dogsglobal. com Mission: Healthy dog breeds Science combined: Conservation genetics (zoos) Livestock breeding genetics Cynology (we are ‘dog-people’) ICT: we have a team in Portugal How to breed healthy: One database per breed Pedigrees from now till founders Automated analyses ▪ including Mean Kinship

www. dogsglobal. com Clubs: Add: Litters and registration-numbers Soon: data on diseases Monitoring Population genetics Future: Breeding Value Estimates