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Brachygnathia Inferior in Cloned Dogs Is Possibly Correlated with Variants of Wnt Signaling Pathway Initiators
Yong-Ho Choe1, Tai-Young Hur2, Sung-Lim Lee1,3
1Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea.
Abstract:
Abnormalities in animals cloned via somatic cell nuclear transfer (SCNT) have been reported. In this study, to produce bomb-sniffing dogs, we successfully cloned four healthy dogs through SCNT using the same donor genome from the skin of a male German shepherd old dog. Veterinary diagnosis (X-ray/3D-CT imaging) revealed that two cloned dogs showed normal phenotypes, whereas the others showed abnormal shortening of the mandible (brachygnathia inferior) at 1 month after birth, even though they were cloned under the same conditions except for the oocyte source. Therefore, we aimed to determine the genetic cause of brachygnathia inferior in these cloned dogs. To determine the genetic defects related to brachygnathia inferior, we performed karyotyping and whole-genome sequencing (WGS) for identifying small genetic alterations in the genome, such as single-nucleotide variations or frameshifts. There were no chromosomal numerical abnormalities in all cloned dogs. However, WGS analysis revealed variants of Wnt signaling pathway initiators (WNT5B, DVL2, DACT1, ARRB2, FZD 4/8) and cadherin (CDH11, CDH1like) in cloned dogs with brachygnathia inferior. In conclusion, this study proposes that brachygnathia inferior in cloned dogs may be associated with variants in initiators and/or regulators of the Wnt/cadherin signaling pathway.
Insights
Cloned dogs exhibited mandibular shortening (brachygnathia inferior) due to genetic variants in Wnt/cadherin signaling pathways. This research identifies potential causes for developmental abnormalities in cloned animals.
Area of Science:
- Animal cloning
- Developmental genetics
- Canine genomics
Background:
- Somatic cell nuclear transfer (SCNT) cloning can result in animal abnormalities.
- Cloned dogs were produced for bomb-sniffing purposes using SCNT.
Purpose of the Study:
- To investigate the genetic cause of brachygnathia inferior (mandibular shortening) in cloned dogs.
- To identify genetic defects associated with developmental abnormalities in SCNT-derived canines.
Main Methods:
- Karyotyping and whole-genome sequencing (WGS) were performed on cloned dogs.
- Genetic analysis focused on identifying single-nucleotide variations and frameshifts.
Main Results:
- No chromosomal numerical abnormalities were found in any cloned dogs.
- Whole-genome sequencing revealed variants in Wnt signaling pathway genes (WNT5B, DVL2, DACT1, ARRB2, FZD 4/8) and cadherin genes (CDH11, CDH1like) in affected dogs.
- Two cloned dogs showed normal development, while two exhibited brachygnathia inferior.
Conclusions:
- Brachygnathia inferior in cloned dogs is potentially linked to variants in Wnt/cadherin signaling pathway components.
- This study highlights the role of specific genetic pathways in SCNT-related developmental defects.
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