Organizer Notes:

Progress has been made and is continuing since the first virtual workshop (held on September 28, 2021-Theme: Standardizing Genetic Testing. Since this meeting, changes have been made to advance the Harmonization of Genetic Testing for Dogs (HGTD) initiative, based on the workshop’s recommendations, and we are still making progress towards more harmonized approaches to genetic testing reports.The focus of the second IPFD Virtual workshop is on genetic diversity (primarily from a genetic tests/tools view), and discussions will aim to identify genetic diversity tools and resources, and discuss priorities and actions for the benefit of dogs. We were thrilled to have a key speaker, Prof. John Woolliams (UK)

Summary of Talks and Key Take-aways from Discussion.

Speakers: Prof. John Woolliams (UK) [Key Note]; Samantha Hauser (Embark, USA), Katy Evans (Guide Dogs, USA), Saija Tenhunen (Viking Genetics, FI), Pieter Oliehoek (Dogs Global, NL), Sally Ricketts (University of Cambridge, UK), and Aimée Llewellyn-Zaidi (IPFD).

Date: 3 May 2022

Summary:

Managing inbreeding is about managing genetic risks, of the unknown and known inherited traits. Mutation effects very rarely (almost never) improve health. They can be neutral, and they can be deleterious in small and significant ways. The breed needs a fixed reference point (e.g. base population) to be defined, by which to measure and monitor changes as well as an understanding of knowing what degree of inbreeding a given breed is starting from (e.g. available genetic material).

Recessive diseases is a consequence of failure to manage inbreeding.

Focusing inbreeding management in near (e.g. 2-5 generations) kinships may be a practical way to address the worst effects of health-risks and inbreeding depression, but long-term management is also important. Goal should be maximum genetic gain (selection) while restricting increasing rate of inbreeding

Concepts/Tools:

IDB (F)

Probability that 2 copies of an allele from the base population (ancestral allele) has been inherited. Often derived from pedigree (e.g. COI).

• You can’t manage inbreeding by F alone.

• You can avoid excessive inbreeding for an individual.

• You can’t assess the breed’s gene pool using F.

Kinships and Relationships

Inbreeding in the breed – calculate F for the breed: probability that 2 alleles sampled at random from the breed are IBD. These pairwise comparisons are called “kinships” or relationships.

Genetic risks for a breed increase with rate of change in F over generations, not F itself (e.g. how fast inbreeding is happening) – effective population size.

Genomic Tools:

IBD can be tracked directly by genomics using markers. Sufficiently dense markers can calculate relationships back to base population. (Breed)

Can also use markers for individual dog’s using runs of homozygosity (ROH) that can approximate recent close inbreeding (individuals)

Drift can measure how much the allele frequencies have changed from the reference base. Drift is important as it determines fixation and genetic loss. Drift has a significant impact on deleterious mutations especially.

Homozygosity can be measured directly by markers – how much (what fraction) of the genome is homozygous vs heterozygous. This is especially relevant for inbreeding depression.

Effects of Genomic Tools:

Restricting Drift = increase loss of rare alleles, faster loss of heterozygosity (rarer alleles might be deleterious or desirable)

Promoting heterozygosity = promotes rare alleles (including deleterious ones), resists fixation of beneficial alleles, increasing inbreeding depression, increases IBD

Tracking IBD = correspondence between drift and loss of heterozygosity, fastest genetic gain, more rapid loss of undesirable alleles and fixing of superior alleles

Inbreeding Management:

• Management by true genomic IBD is an optimal tool.

• Manage the breeding population as a whole – managing the gene pool cannot be done in isolation. Breeders must work collectively.

• Restricting the rate of inbreeding requires restricting the long-term impact of individual dogs (e.g. popular sires/dams) – e.g. limit registered offspring numbers from over-represented dogs.

• Key recommendations - promote a wide-range of offspring for breeding from; use more healthy dogs.