Animal Molecular Breeding 2024, Vol.14, No.4, 280-287 http://animalscipublisher.com/index.php/amb 283 the breed's other desirable characteristics, such as its robust health, friendly personality, and striking appearance (Abitbol et al., 2024)). The development of the Siberian cat as a hypoallergenic breed was largely unintentional at first, but breeders have since recognized and enhanced this trait, making the Siberian one of the few breeds specifically known for its hypoallergenic potential. While not every Siberian cat will be hypoallergenic, the breed’s overall lower production of Fel d 1 has established it as one of the most popular hypoallergenic breeds (Salonen et al., 2019). 4.3 Challenges and limitations in hypoallergenic cat breeding Breeding for hypoallergenic traits in cats presents several challenges and limitations. One major difficulty is the genetic complexity of allergen production. The inheritance patterns of hypoallergenic traits are not fully understood, as the production of Fel d 1 and other allergens is influenced by multiple genes. This makes it difficult to predict the allergenic potential of offspring, even when breeding from hypoallergenic lines. Furthermore, variability in allergen levels within hypoallergenic breeds remains a significant challenge. Not all individuals within a breed like the Siberian cat will produce the same low levels of allergens, and some may still trigger allergic reactions (Brackett et al., 2022). Additionally, selective breeding focused solely on hypoallergenic traits can lead to ethical concerns about inbreeding and its potential consequences, such as a reduced gene pool and the increased risk of genetic disorders. While hypoallergenic breeding aims to produce cats with fewer allergens, it is important to balance this goal with the long-term health and genetic diversity of the breed. Moreover, environmental factors, such as diet, grooming, and general health, can influence allergen production, further complicating the breeding process. Despite these efforts, achieving a completely hypoallergenic cat remains elusive, as even hypoallergenic breeds can produce sufficient allergens to trigger reactions in some sensitive individuals (Thoms et al., 2020; Bienboire-Frosini et al., 2020). 5 Genomic Technologies in Hypoallergenic Cat Breeding 5.1 Use of genetic testing in identifying hypoallergenic traits Genetic testing plays a crucial role in identifying hypoallergenic traits in cats by analyzing the distribution and frequency of genetic variants associated with allergens. For instance, extensive panel testing has been used to identify disease-associated variants across various cat breeds, which can be instrumental in reducing allergen levels through selective breeding. The use of high-throughput SNP genotyping technologies, such as the feline 63K DNA array, has improved the genetic dissection of traits, allowing breeders to identify and select for hypoallergenic traits more efficiently. These technologies enable breeders to assess genetic diversity and identify specific markers associated with hypoallergenic traits, thereby supporting breeding programs aimed at reducing allergens like Fel d 1 (Figure 2) (Gandolfi et al., 2018; Anderson et al., 2021). Figure 2 A)The signature "smile" of a cat with Myotonia Congenita; B) The rare coat color phenotype Amber in a random-bred cat from Finland; C) Polydactyly variant Hw also associated with extra toes in all four feet. Photo credit (from A to C): Kimberly Sullivan, Ari Kankainen, Samantha Bradley (Adopted from Anderson et al., 2021) 5.2 CRISPR and gene-editing technologies for hypoallergenic traits CRISPR-Cas9 technology has emerged as a powerful tool for creating hypoallergenic cats by enabling precise gene editing. Recent studies have demonstrated the successful use of CRISPR to knock out the CH2 gene in cats, resulting in significantly reduced levels of the major allergen Fel d 1 (Lee et al., 2023). This gene-editing approach offers a promising avenue for developing hypoallergenic cats by directly targeting and modifying the
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