A DNA Primer for Dog Breeders - Genetic Diversity: Heterozygosity

By Carol Beuchat PhD
One of the most basic things to know both about a breed and an individual dog is genetic diversity. In a breed, genetic diversity is the variation in DNA that results in the differences in traits from individual to individual. Genetic diversity also allows populations to adapt or evolve in the face of changes in the environment or disease.
In an individual animal, genetic diversity is realized in the fraction of loci that are heterozygous. Inbreeding increases the fraction of loci that are homozygous, and this in turn raises the risk of the expression of a recessive genetic disorder. Homozygosity also results in an overall deterioration in health referred to as "inbreeding depression". So, at both the individual and population (i.e., breed) levels, it is important for breeders to be monitoring genetic diversity.
There are several different ways to assess genetic diversity using SNP data. Below I will describe how each is estimated, what the data mean, and how breeders can use the information.

Heterozygosity (Ho)

A very common method of assessing genetic diversity from DNA data is by computing heterozygosity.
A locus with two copies of the same nucleotide (e.g., AA, aa) is homozygous. A locus with two different nucleotides (Aa) is heterozygous. This is part of the data spreadsheet from SNP genotype which lists the genotypes found at 4 SNP markers (e.g., BICF2G...., etc) on the chromosomes of 12 dogs (one in each row).

For the first marker (column 618), you can see that some dogs are homozygous for that SNP (either AA or GG), while some are heterozygous (AG). For the next two SNPs, all but one of the dogs are homozygous for the same nucleotides, and all of the dogs are homozygous at the last marker.

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We can determine the degree of heterozygosity of each of these markers by tallying up the different combinations of alleles for each marker in each of the dogs in our sample. From these information, we can then compute heterozygosity, which is simply the fraction of all of the marker that were heterozygous, averaged over all of the dogs. The higher the heterozygosity, the greater the genetic diversity. This is usually referred to as "observed heterozygosity" (Ho).
The graphs below show the frequency distribution of observed heterozygosity (Ho) determined for dogs in four different breeds: the Labrador and Golden Retrievers, the Coton de Tulear, and the Stabyhoun. You can see immediately that although there are dogs in both of the retrievers with low heterozygosity (0.2 or lower), there is some variation in the population such that the distribution extends up to about 0.35. The average and minimum Ho are similar to these in the Coton de Tulear, but the highest heterozygosity is about 0.3. The population of Stabyhoun has the lowest heterozygosity with most individuals less than about 0.25 and little variation around the mean of 0.2.
The data for heterozygosity for these four breeds reveal that the Labrador and Golden have the highest average heterozygosity, the Coton de Tulear, somewhat less, and the Stabyhoun the least. Individual dogs with the highest values for Ho will produce puppies with lower levels of inbreeding on average than dogs with lower Ho.

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Inbreeding

Most breeders are familiar with Wright's Coefficient of Inbreeding (COI), which is calculated from pedigree data. The COI provides an estimate of the predicted level of inbreeding based on the simple assumptions that alleles are inherited independently and with equal probability. From this, you can predict the COI of a dog based just on the pedigree data (providing it is accurate and complete) as well as the average COI of a litter of puppies. Because COI is based on the probability of inheriting alleles across all generations of a pedigree, it cannot estimate the COI of a dog exactly. However, it usually correlates well enough with "actual" inbreeding (based on DNA homozygosity) that it remains the single most useful statistic used by animal and plant breeders to assess the level of inbreeding in an individual or the inbreeding to be expected in progeny.

If pedigree data are incomplete, or you need a more accurate estimate of inbreeding than is computed using COI, inbreeding can be estimated directly from DNA. Of course, heterozygosity that we discussed above is related to inbreeding as

Ho = 1- homozygosity.

However, there are some additional methods of estimating inbreeding that can also tell us about how inbreeding is distributed over the chromosomes and how long ago it occurred. This is done by looking for "runs of homozygosity" (ROH) - regions of the chromosomes where there are many conse... homozygoous loci. Inbreeding doesn't produce inbreeding that is randomly scattered all over the chromosomes. Selection, both natural and artificial, will produce "hot spots" of homozygosity in the regions of the chromosome where genes under selection are located. If the genes remain under continuous selection, the ROH will get longer and longer every generation.

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