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Gene or Region: FKBP6
Reference Variant: G (iar1), C (iar2)
Mutant Variant: A (iar1+iar2)
Affected Breeds: Thoroughbred
Research Confidence: Preliminary - Initial study had low number of horses, expanded study in progress
Explanation of Results: iar1/iar1, iar2/iar2 = four Impaired Acrosomal Reaction Subfertility alleles detected, may be affected (males/stallions only) iar1/iar1, iar2/n = three Impaired Acrosomal Reaction Subfertility alleles detected, no known effect n/iar1, n/iar2 = two Impaired Acrosomal Reaction Subfertility alleles detected, no known effect n/n, n/iar2 = one Impaired Acrosomal Reaction Subfertility allele detected, no known effect
In normal fertilization, the the head of a sperm binds to the egg and releases the contents of a structure known as the acrosome. However, some males have otherwise normal sperm that are unable to properly carry out this process, leading to sub- or infertility due to impaired acrosome reaction. Very little is known about the genetics of male fertility. One study of 7 horses with known IAR, 87 known fertile stallions, and 171 male horses of unknown fertility status found an association with two SNPs in the FKBP6 gene. All 7 case stallions had genotype A/A for both, as compared to only 2 known fertile stallions and 3 unknown fertility males. The authors noted that fertility was defined as having at least one foal, though even males with IAR can rarely produce offspring.
FKBP6 is a binding protein involved in replication of sperm and possibly fertilization. Though not much is known of its specific actions, mouse and rat mutants are unable to produce sperm, and human variants have been associated with impairments in sperm production. This gene is only expressed in males, and expression has only been detected in testis and ejaculate. The two mutations (IAR1, IAR2) do not appear to alter the structure of FKBP6, though they may play a role in its regulation. In humans and mice FKBP6 was also studied and found related to sperm issues.
As Impaired Acrosomal Reaction is thought to be "multi-allelic" (meaning it involves multiple alleles or genomic sites as opposed to just one), only male horses with the IAR mutation in all four alleles, in both regions, are thought to be possibly affected. Simply put: to be at risk, your graph will appear with two completely red bars indicating homozygosity in both regions for the IAR risk allele.
This study/allele set has only been conducted in Thoroughbred horses, the effects are yet unknown in other breeds.
Raudsepp T et al., “Genome-wide association study implicates testis-sperm specific FKBP6 as a susceptibility locus for impaired acrosome reaction in stallions.” (2012) PLoS Genet. 8: e1003139. PMID: 23284302
Junctional Epidermolysis Bullosa (JEB), also known as red foot disease or hairless foal syndrome, results in the inability to produce the proteins needed to keep the skin on the body. Affected foals exhibit symptoms within days of birth, including blisters at the pressure points, detatchment of the hooves, and oral ulcers. As there is no treatment, affected foals are humanely euthanized.
Kissing Spines Susceptibility (KSS) evaluates a horses genetic risk for developing Kissing Spines. Horses diagnosed with Kissing Spines will have two or more dorsal spinous processes that are too close together, touch, or even overlap. This bone-on-bone grinding causes varying degrees of pain, and thus decreased mobility.
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