Genomic Inbreeding Coefficient (GIC, g-COI)

The genomic inbreeding coefficient is best determined by analysing SNP arrays (single nucleotide polymorphism) or whole genome sequencing (WGS), using as many individual SNPs as possible that are evenly distributed across the genome. The GIC reported by Generatio is a ROH-based genomic inbreeding coefficient and corresponds to the value commonly referred to in the scientific literature as F_ROH (McQuillan et al. 2008).

In the first step, the ROH (runs of homozygosity) are identified from the SNP genotypes, i.e. longer stretches in which the animal is homozygous throughout. The lengths of all ROH are summed and divided by the length of the genome covered by the ROH analysis (sex chromosomes are usually excluded). The result is a percentage, the GIC. The higher the GIC of the animal analysed, the more of its genome is homozygous as a result of inbreeding.

Comparability: How high the GIC turns out also depends on the parameters of ROH detection, above all the minimum length from which a segment is counted as a ROH, and on the SNP density of the array. GIC values from different laboratories or methods are therefore not directly comparable.

The GIC indicates the realised proportion of the genome that is homozygous (autozygous) as a result of inbreeding. This is the difference to the pedigree-based inbreeding coefficient (F_PED), which can only indicate the proportion expected on average. Due to Mendelian sampling, however, the proportion actually inherited varies from animal to animal, even between full siblings; the GIC measures it.

This applies to all genes, i.e. to desirable performance traits and breed-specific characteristics as well as to the inheritance of deleterious recessive alleles.

The higher the GIC, the greater the inbreeding and the higher the probability that rare deleterious recessive alleles also come together in the homozygous state and are expressed.

The GIC also allows a conclusion as to the theoretical relationship between the parents of the animal analysed, provided that these parents were not themselves the result of inbreeding.

Examples:

Purebred dogs show high average levels of genomic inbreeding; a study of more than 200 breeds found an average of around 25 %, with large differences between breeds (Bannasch et al. 2021). This shows that the individual breeds have been established through inbreeding and that breed-typical characteristics have then been consolidated through continued inbreeding.

A value of 25 % therefore does not mean that a full-sibling mating took place. The value has more likely arisen through cumulative inbreeding over many generations. This also explains GIC values of over 40 %, which are observed in some breeds with a small population size or pronounced continued inbreeding. Whether the inbreeding is recent or ancient is shown by the length of the ROH: long ROH originate from matings a few generations back, short ROH from inbreeding in the distant past (see ROH profiles).

Both the genomic inbreeding coefficient and genomic heterozygosity are building blocks for assessing genetic diversity and health, but they provide different information that complement each other.

The two are closely linked: the larger the proportion of the genome that is homozygous due to inbreeding, the lower the heterozygosity as a rule. The heterozygosity value shows the overall genetic diversity of the animal analysed, but does not indicate which part of the homozygosity is due to inbreeding and where in the genome it lies.

Together with the ROH profiles, the GIC is the basis for breeding strategies that avoid inbreeding in individual matings or reduce it in a population with an already threatening level of inbreeding.

The GIC is part of the 'Inbreeding & Diversity' assessment. For this purpose, Generatio carries out SNP array genotyping and, in addition to the GIC, determines the HE value and the ROH profile. The assessment is currently available for dogs, horses and camelids.

Single tests:

• Dog:Inbreeding & Diversity (Fitness) Dog
• Horse:Inbreeding & Diversity (Fitness) Horse
• Camelids:Inbreeding & Diversity (Fitness) Camelids

Bundles including inbreeding analysis:

• Dog:SNP Profile Identity & Inbreeding & Fitness Dog: DNA identity and inbreeding analysis
• Dog:ProLine Bundle Dog: DNA identity, inbreeding and diversity analysis and breed analysis
• Horse:Bundle Breed Analysis, Identity, Inbreeding Assessment
• Horse:MIM-6-Var. plus Inbreeding & Fitness: test for the six MIM variants and inbreeding analysis
• Dromedary:Bundle DNA Identity and Inbreeding Analysis Dromedary

Lexicon:

• Genomic Heterozygosity
• ROH Profiles
• Popular Sire Syndrom

Literature:

• McQuillan, R., Leutenegger, A.-L., Abdel-Rahman, R. et al.: Runs of homozygosity in European populations.Am J Hum Genet 83:359-372, 2008. DOI: 10.1016/j.ajhg.2008.08.007
• Ceballos, F.C., Joshi, P.K., Clark, D.W., Ramsay, M., Wilson, J.F.: Runs of homozygosity: windows into population history and trait architecture.Nat Rev Genet 19:220-234, 2018. DOI: 10.1038/nrg.2017.109
• Bannasch, D., Famula, T., Donner, J., Anderson, H. et al.: The effect of inbreeding, body size and morphology on health in dog breeds.Canine Med Genet 8:12, 2021. DOI: 10.1186/s40575-021-00111-4
• Nishio, M., Inoue, K., Ogawa, S. et al.: Comparing pedigree and genomic inbreeding coefficients, and inbreeding depression of reproductive traits in Japanese Black cattle.BMC Genomics 24:376, 2023. DOI: 10.1186/s12864-023-09480-5