Resources and insights

After two decades in the veterinary medical field, I’ve witnessed countless treatment protocols, diagnostic advances, and management trends. Yet nothing has transformed my understanding of equine health quite like muscle myopathies. These complex conditions—PSSM1, MIM and its variants, MFM, MYHM, and so forth—have become unexpected catalysts, revealing fundamental truths about health that extend far beyond the horses they affect. What makes these conditions so instructive isn’t their complexity, it’s their honesty. Unlike many equine ailments that respond to pharmaceutical intervention, muscle myopathies strip away our comfortable reliance on medical management. They demand something more fundamental: a return to species-appropriate nutrition, natural movement patterns, and collaborative care that honors the whole horse. When Medicine Meets Its Match In my years as an equine nutrition professional, I’ve consulted on hundreds of muscle myopathy cases. The pattern is strikingly consistent: owners arrive having tried every supplement, every medication, every promise of a solution. Their horses continue to struggle. Not because the veterinary care was inadequate, but because these conditions require something medicine alone cannot provide. This is where beauty emerges from the burden. When conventional treatments offer minimal relief, we’re forced to examine our husbandry practices and whether our convenient systems serve the…

When you’ve exhausted all your resources and drained your back account, trying to find what is wrong with your horse, then what do you do? You dig a little deeper, research longer and keep asking questions. You get told you are crazy, your horse has got the better of you, and mostly you are making stuff up. You consider euthanasia but the good days come and you are left feeling hopeful and yet still frustrated.  Here is the story of my beloved Tuned up Whiz it, aka Whizzy.  Her current diagnosis is PSSM type 2 via biopsy and n/P2, n/Px n/MYHM via EquiSeq DNA testing. I met Whizzy the fall of 2009, she was 4 years old. Her price was way out of my range due to her breeding and intense training to be a reining  horse.  Whizzy just could not spin in one direction fast enough to meet the needs of the owner. She needed to move her fast as she had already bought another 2 year old. I took her on trial and I had x-rays that revealed some changes in her right front hoof, my farrier thought it no big deal. I  made a super low offer…

Introduction This blog post explores the K1 allele of the equine COL6A3 gene, which encodes Collagen type VI alpha 3 chain. Portions of this blog post serve as additional sources of information to supplement the COL6A3 Gene Page. The K1 allele of COL6A3 carries a missense mutation, shown below. The protein model XP_014595871.3 was used to assign amino acid positions. Figure 1. Alignment of partial COL6A3 protein sequences from horse, compared to the K1 variant. The position of the amino acid affected by the substitution is highlighted in red. We present data to support the hypothesis that the K1 allele of COL6A3 is damaging. The K1 variant (G1976A) substitutes an alanine for a glycine. The affected amino acid is in the triple-helical portion of COL6A3. The general sequence of this region in all collagens is GLY-X-Y, where every third amino acid is a glycine. The X and Y amino acids are generally poorly conserved. In the formation of the collagen triple-helical region, the glycine residues are points of contact between helices. Glycine has the smallest R group of any amino acid (a hydrogen atom). Other amino acids in these positions interfere with triple helix formation to some extent. For further discussion,…

Introduction This blog post explores the P3 allele of the equine FLNC gene, which encodes filamin-C. Portions of this blog post serve as additional sources of information to supplement the FLNC Gene Page. The P3 allele of FLNC carries two missense mutations, shown below. The protein model XP_023495410.1 was used to assign amino acid positions. Figure 1. Alignment of partial FLNC protein sequences from horse, compared to the P3a and P3b variants. The positions of the amino acids affected by the two substitutions are highlighted in red. We present data to support the hypothesis that the P3 allele of FLNC is damaging. For the P3a variant (E794K), the substitution of lysine (positively charged) for glutamic acid (negatively charged) is a somewhat conservative substitution. For the P3b variant (A1248T), the substitution of threonine (polar uncharged) for alanine (hydrophobic) is a nonconservative substitution. Evolutionary conservation provides convincing evidence that the P3 allele of FLNC is damaging.  We use public data to show that the reference allele of P3a (E794) is highly conserved across 389 species of mammals, birds, reptiles, amphibians, and fish representing 29 unique sequences of the 41-amino acid query sequence centered on the position of the E794K allele, covering about 400…

Introduction This blog post explores the P4 allele (S42L) of the equine MYOZ3 gene, which encodes myozenin 3. Portions of this blog post serve as additional sources of information to supplement the MYOZ3 Gene Page. We present data to support the hypothesis that the P4 allele of MYOZ3 (S42L) is damaging. The substitution of leucine (hydrophobic) for serine (polar uncharged) in the P4 allele of MYOZ3 is a nonconservative substitution of a chemically dissimilar amino acid.  Evolutionary conservation provides convincing evidence that the P4 allele of MYOZ3 is damaging. We use public data to show that the reference allele is completely conserved across 448 species of mammals and birds representing 155 unique sequences of the 41-amino acid query sequence centered on the S42L allele, covering over 310 million years of evolutionary history.  P4 allele of equine MYOZ3 Evolutionary conservation provides evidence on whether the P4 allele of MYOZ3 is damaging. In this approach, predicted MYOZ3 protein sequences are compared among a number of different species. This method, applied to mammals and birds, is shown below. A 41 amino acid segment of the protein sequence of equine MYOZ3 (XP_005599348.1), centered on the position of the variant, is shown below. This sequence is compared to…

Introduction This blog post explores the P2 allele (S232P) of the equine MYOT gene, which encodes myotilin. Portions of this blog post serve as additional sources of information to supplement the MYOT Gene Page. We present data to support the hypothesis that the P2 allele of MYOT (S232P) is damaging. The substitution of proline (heterocyclic) for serine (polar uncharged) in the P2 variant of MYOT is a nonconservative substitution of a chemically dissimilar amino acid. Evolutionary conservation provides convincing evidence that the P2 allele of MYOT is damaging. We use public data to show that the reference allele is widely conserved across most of 244 species of mammals and birds covering over 310 million years of evolutionary history. There is a prominent exception in humans, where the MYOT gene has a conservative amino acid substitution that has gone to fixation (S232T). The substitution of threonine (polar uncharged) for serine (polar uncharged) in human MYOT is a conservative substitution of a chemically similar amino acid. This variant has gone to fixation in all the great apes most closely related to humans (chimp, bonobo, gorilla, and orangutan), but is absent from Old World monkeys, placing the origin in the common ancestor to…