Prevalence of the Mutations Responsible for Glanzmann Thrombasthenia in Horses in Brazil

Abstract

Simple SummaryHereditary bleeding disorders occur in different species due to mutations in genes coding specific hemostatic proteins leading to alterations in their synthesis, or to the production of non-functional proteins which leads to impairment of hemostasis. Some of these disorders have been described in horses, i.e., Von Willebrand disease (VWD), hemophilia A, and Glanzmann’s thrombasthenia (GT). GT is an inherited disease characterized by hemorrhage and has been described in different species including horses of varied breeds (Thoroughbred, Standardbred, Oldenburg, Peruvian Paso, and Quarter Horse). There are two different mutations described in horses a single guanine to cytosine substitution (CGG for CCG) and a 10 base pair deletion in the ITGA2B gene.AbstractGlanzmann’s thrombasthenia (GT) is an autosomal recessive inherited disorder characterized by changes in platelet aggregation, leading to hemorrhage and epistaxis. To date, two independent mutations have been described in horses and associated with this disorder, a point mutation (c.122G > C) and a 10-base-pair deletion (g.1456_1466del) in the Integrin subunit alpha2β gene (ITGA2B) of horses of different breeds (Quarter Horse, Thoroughbred, Oldenburg, and Peruvian Paso). ITGA2B codifies the αIIb subunit of the αIIbβ3 integrin, also termed platelet fibrinogen receptor. Horses with GT have been diagnosed in the USA, Canada, Japan, and Australia. However, there are no studies on the prevalence of GT in horses. The aim of this study is to evaluate the prevalence of the mutations responsible for GT in horses in Brazil. A total of 1053 DNA samples of clinically healthy Quarter Horse (n = 679) and Warmblood horses (n = 374) were used. DNA fragments were amplified by PCR and sequenced. The genotype of each animal was analyzed and compared to the nucleotide sequence of the ITGA2B gene found on GenBankTM. There were no carriers in the analyzed samples, that is, all animals tested were wild type. Therefore, under the conditions in which this study was carried out, it can be inferred that GT seems to be extremely rare in the population of Quarter Horses and Warmbloods in Brazil, although it is not possible to affirm that there are no horses carrying mutated alleles in Brazil.

Prevalence of the E321G MYH1 variant in Brazilian Quarter Horses

“…The allele frequency of the E321G MYH1 variant in QHs in Brazil was estimated to be 0.074, which is twice as high as the frequency observed in 146 randomly selected QHs in the USA and Canada (0.034) and is more similar to that observed in elite performance QHs in the USA (0.049). 9 As observed for MYH1, the frequencies of alleles involved in other genetic diseases, that is, PSSM1, 4 HYPP, 10 GBED 13 and hereditary equine regional dermal asthenia (HERDA), 14 in Brazilian QHs were also similar to those found in American QHs. 3 The results obtained in this study and in previous studies 4,10,11,15 suggest that the similarity in the allele frequencies of these mutations may be because Brazilian QHs are often closely related to American QHs 14 and reining is a popular discipline in both countries.…”

“…As observed for MYH1 , the frequencies of alleles involved in other genetic diseases, that is, PSSM1, 4 HYPP, 10 GBED 13 and hereditary equine regional dermal asthenia (HERDA), 14 in Brazilian QHs were also similar to those found in American QHs 3 . The results obtained in this study and in previous studies 4,10,11,15 suggest that the similarity in the allele frequencies of these mutations may be because Brazilian QHs are often closely related to American QHs 14 and reining is a popular discipline in both countries.…”