Brachygnathia Inferior in Cloned Dogs Is Possibly Correlated with Variants of Wnt Signaling Pathway Initiators

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.

Genome-Wide Characterization of Somatic Mutation Patterns in Cloned Dogs Reveals Implications for Neuronal Function, Tumorigenesis, and Aging

“…We refer to specific variations observed uniquely in cloned dogs, distinct from the donor, as somatic mutations. In our previous study, cloned dogs were generated using Somatic Cell Nuclear Transfer (SCNT) from a donor [ 17 ]. Whole genome sequencing data were obtained by using the Illumina sequencing platform to analyze the blood of the donor and its cloned dogs (NT2 and NT4), which were clinically diagnosed as completely normal.…”

“…In another study, cloned dogs were produced via SCNT using ear fibroblasts from a 5-year-old male German Shepherd [ 17 ]. Whole genome sequences of the original dog were generated from the whole blood of a 6-year-old German Shepherd.…”