Pelger-Huet Anomaly

In Australian Shepherd Dogs

What is Pelger-Huet Anomaly?

PHA is an incompletely dominant genetic disorder that causes the nuclei of white blood cells to be abnormally shaped and structured. It is usually lethal in homozygous dominant individuals, and heterozygous individuals are typically healthy and function normally. There are no phenotypic indicators that an individual has the disease.

It should not be confused with pseudo-Pelger-Huet Anomaly, which can result from myeloid leukemia, myelodysplasia, and bi-lineage acute lymphocytic leukemia, after considerable chemotherapy treatments, as well as certain deficiencies or excesses of substances. It is not a heritable disease, but appears very similar to the true Pelger-Huet Anomaly.

What Causes Pelger-Huet Anomaly?

In dogs, the lethal form is an autosomal dominant inherited gene, inherited from seemingly-healthy heterozygous adults. It has a 25% chance of occuring when two heterozygotes are bred. Because the disorder has incomplete penetrance, it is difficult to regulate breeding stock for carriers without blood smear tests of each of them prior to breeding. The disorder in adults is typically discovered while completing complete blood counts or biochemistry profiles for other purposes.

It is similar to the double merle gene in Australian Shepherds in its lethal form, and is thought to have developed because genes have been inadvertently concentrated due to selective breeding.

Cellular Structure

The gene responsible for the Pelger-Huet anomaly is the LBR (Lamin B receptors) gene on subband 1q42.1, first discovered in crossbreeding experiments with rabbits in Germany. The gene product of LBR is responsible for maintaining nuclear membrane structure. Homozygous dominant individuals have very coarsely and tightly bound neutrophils that are typically not capable of normal function. Heterozygous individuals have neutrophils with lobed, dumbell shaped nuclei, also called "pince-nez" because of their similarity to pinched nose spectacles.

LBR interacts with the heterochromatin proteins, which is thought to be the cause for the excessive clumping of chromatin observed. These abnormalities in heterozygous individuals do not seem to effect neutrophil function and the cells can phagocytize normally. Homozygous individuals are very rare, but when they do occur, have neutrophils that are a single round shape with eccentric nuclei, clumped chromatin, and and little to no segmentation.

Homozygous vs. Heterozygous Individuals

Individuals who receive the dominant (PP) homozygous genes are typically reabsorbed in the uterus, stillborn, or die shortly after birth. This has a large impact on breeders because it reduces litter size, but close to no effect on the long term dog owners because heterozygotes function normally.

In the very rare case that a homozygous individual does survive past puppyhood, it is susceptible to skeletal anomalies, developmental delays, and seizures.

Discussion Point...

What precautions would you take while arranging breedings if you were a prestigious Australian Shepherd breeder, and your prize, award winning sire was a heterozygous carrier of the Pelger-Huet Anomaly?

Is it ethical or worthwhile to breed to another heterozygous female carrier who was equally prestigious in her awards and accomplishments, if her owner approached you and asked if you would allow a breeding to your sire?


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