A Unique Case of Mosaicism for Two Robertsonian Translocations, rob(17;27) and rob(17;29), in a Subfertile Mare (Equus caballus).

Overview

• This study reports a unique case of a subfertile mare (Equus caballus) exhibiting mosaicism for two distinct Robertsonian translocations involving chromosomes 17, 27, and 29.
• The research highlights the genetic and clinical characteristics of this rare chromosomal rearrangement in horses and explores its implications for fertility and chromosome biology.

Introduction to Robertsonian Translocations (ROBs)

• ROBs are structural chromosomal rearrangements common in mammals where two acrocentric chromosomes fuse at their centromeres, forming a single chromosome.
• These rearrangements are medically significant as they are associated with subfertility and congenital disorders across various species.
• While common in species like humans, mice, and cattle, ROBs are extremely rare in horses despite their karyotype having multiple acrocentric chromosomes (18 in horses).

Case Description and Methods

• The subject is a horse mare with clinical signs of subfertility such as small ovaries, irregular heat cycles (estrus), and a history of two pregnancy losses.
• Conventional cytogenetic techniques (like chromosome banding), molecular cytogenetic approaches, and DNA analysis methods were used to characterize the chromosomal abnormalities.
• The molecular characterization allowed identification of the specific chromosomes involved and the nature of the translocations.

Key Findings

• The mare showed mosaicism, meaning two different cell lines existed within the same individual:
• One cell line with 63 chromosomes including a Robertsonian translocation between chromosomes 17 and 27 (designated rob(17;27))
• Another cell line with 63 chromosomes including a Robertsonian translocation between chromosomes 17 and 29 (rob(17;29))
• No normal karyotype cells were detected; all cells had one of the two types of ROBs.
• Both derivative chromosomes formed by these translocations retained two structural centromeres, a feature typical also seen in human and bovine ROBs.
• This is the first reported instance of a nonhomologous chromosome ROB in horses and the presence of mosaicism for two distinct ROBs in the same individual.

Clinical Implications

• The mare’s subfertility symptoms align well with previously reported effects of ROBs in other animals.
• Small ovary size, irregular estrus cycles, and pregnancy losses indicate that these chromosomal abnormalities can significantly impact reproductive success.
• This suggests that ROBs may be an underrecognized cause of fertility issues in horses.

Biological and Evolutionary Significance

• ROBs contribute to chromosomal evolution by changing the structure and number of chromosomes over generations.
• The study draws attention to the role of centromeric satellite DNA — repetitive DNA sequences located around centromeres — in forming ROBs, as these sequences may facilitate fusion events.
• Despite horses having a high number of acrocentric chromosomes, ROBs are rare, hinting at species-specific genomic or molecular features that influence the formation of such translocations.
• Further molecular studies on this mosaic mare could shed light on the nature of centromeric satellite sequences that either encourage or prevent Robertsonian fusions.

Conclusions and Future Directions

• This is a novel and unique case highlighting mosaicism for two distinct Robertsonian translocations in a horse, expanding knowledge of chromosomal abnormalities in equine genetics.
• The findings emphasize the need for further molecular and genomic analysis to understand the mechanisms behind ROB formation and their association with fertility.
• Understanding the role of centromeric regions may help explain species differences in ROB frequency and contribute to veterinary diagnostics and management of subfertility in horses.