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Matching DNA

Matching nuclear DNA to mitochondrial DNA

The final part of Alan Porter’s in-depth report on the latest genetic science and how breeders should use this knowledge to decide on mating plans

IN PEDIGREE TERMS when we consider the tail-female line of a mare (representing the mitochondrial line) and then look at the rest of the pedigree (representing the nuclear DNA) of an individual or a proposed mating we want to see a structure that indicates that the foal will have a high chance of inheriting nuclear DNA that fits the mitochondrial line of the mare.

We have all looked down at a catalogue page and seen instances where a particular sire or sire-line has had an outweighed influence on the superior runners found in the female lineage noted on the page, but we should note here, that the nuclear DNA can come from either side of the pedigree, which is an important factor when considering matings.

So, if we look at a mare such as Immortal Verse we see she is from the L haplogroup (annotated in red, see pdf)

Her sire, Pivotal, and his sire Polar Falcon, are both also from the L haplogroup, and since they were both high-class runners, the odds are that they possessed nuclear DNA that combined well with the L haplogroup mitochondria.

When we come to Side Of Paradise, the dam of Immortal Verse, we see that three of her four grandparents are from the L haplogroup, a statement that also applies to Immortal Verse’s grand-dam, Mill Princess.

This means there is a very high chance that Immortal Verse, a superior runner, has the nuclear DNA that fits the L mitochondrial haplogroup in double copy i.e. she is homozygous (she has inherited the same versions of a genomic marker from each biological parent).

So from the nuclear/mitochondrial standpoint she is an “independent unit” meaning her foals should inherit the nuclear DNA to fit the L haplogroup, irrespective of her mates.

Immortal Verse has now produced, in consecutive years, the Cheveley Park Stakes (G1) heroine Tenebrism (by Caravaggio whose sire and dam are from the N and G haplogroups) and the 2022 Airlie Stud Stakes (G2) winner Statuette (from the first crop of Justify, whose sire and dam are both from the N haplogroup).

If we take a mare such as La Petite Virginia (see overleaf) we see that she has a far more heterozygous (she has inherited different versions of a genomic marker from each biological parent) background – in fact her grandparents are from four different mitochondrial haplogroups – which means an ideal mating for her would be with a stallion that reinforces her G mitochondrial haplogroup, something that is absent in her own nuclear pedigree.

Her mating with Ruler Of The World, which produced the recent Pretty Polly Stakes (G1) winner La Petite Coco, did just that as Ruler Of The World is by Galileo, who is also from the G mitochondrial line.

We might also observe that Galileo is by Sadler’s Wells, who is from the D haplogroup, implying that the same nuclear DNA might well work with both G and D mitochondrial lines something that is further suggested out by the fact that La Petite Virginia’s granddam, the German champion La Dorada, is also by a stallion from the D haplogroup from the G mitochondrial family.

This all brings us to the question of how what we have discovered about mitochondria – its importance to athletic performance, and the need for the right nuclear DNA to combine with the mitochondrial DNA – can be practically employed in evaluating a pedigree or planning a mating?

It certainly isn’t a simple matter for a breeder wishing to take this very important factor into consideration when planning a mating or for someone selecting prospects from the sales. The mitochondrial haplotypes of individuals aren’t currently listed in the General Stud Book, and given the number of errors in the tables of descent based on Bruce Lowe’s system, and its discordance with actual mitochondrial DNA, that utilizing his family numbers isn’t a solution.

...there is a very high chance that Immortal Verse, a superior runner, has the nuclear DNA that fits the L mitochondrial

I will declare something of an interest as a partner with Byron Rogers in the company Performance Genetics. He and his company has done much of the work establishing the true mitochondrial descent of the breed, and is now able to offer a practical way of considering mitochondrial lines of descent in a pedigree.

Performance Genetics has been established for more than decade, evaluating thoroughbreds utilising machine learning to analyse biomechanical (from a short-walking video), cardiovascular and DNA data.

Now it has now created a programme to analyse thoroughbred pedigrees.

Named Molecular Matings, this soon-to-be-publicly-available programme has an ever-growing database of over 500,000 thoroughbreds and the results of nearly 100,000 individual stakes events.

we can now say with an extremely high degree of certainty from which mitochondrial DNA line any individual horse stems

What is unique about this database is that as a result of extensive DNA testing of over 5,000 horses, finding diverse samples in order to trace them back to a distant most common recent ancestor in the General Stud Book, it also contains the true mitochondrial haplotype of almost all the modern female families.

Following the adoption of DNA testing in the 1970s and 80s as a criteria for registration into the stud books worldwide, ensuring the veracity of modern pedigrees, we can now say with an extremely high degree of certainty from which mitochondrial DNA line any individual horse stems.

The mitochondrial DNA of the horse and it’s immediate ancestors – which points to the degree of likelihood of there being compatibility between the nuclear and mitochondrial – is also vital component of the machine learning programme within Molecular Matings.

It considers numerous other factors, based on pedigree data (also including relationships between various individuals in the pedigree, Wright’s Coefficients of Inbreeding, and the Ancestral History Coefficient as proposed by Baumung and colleagues); the performance and production data of immediate ancestors (including proprietary ratings for individual runners, for sires, grandsires and broodmare sires); and the presence or lack of proven affinity between individuals in the pedigree.

The machine learning analysis of the data – including for the first time, reliable mitochondrial haplotype information – to rate the pedigree in terms of potential to produce an elite runner is the unique feature of the programme.

Molecular Matings does also include all the functions one would expect from a pedigree research programme, including the ability to look at individual pedigrees and hypothetical pedigrees; to search stakes winners by sire, sire line, broodmare sire or broodmare sire line; to search for horse bred on specific crosses or containing specific ancestors; and female line searches.

It’s all a long way in time and complexity from the work of Bruce Lowe, but I’ve got a feeling that he’d be happy to find that he was much nearer the mark than the mid-20th century debunkers would have believed.

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