Gene Mutations Related to Polycystic Kidney Disease in Cats Confirmed to Be on the Decline

Anicom Phar株式会社 (President and CEO: Shoichiro Koga, hereinafter "the Company"), in collaboration with Anicom Advanced Medical Research Institute Inc., Anicom General Insurance Company Limited, and Azabu University (President: Ken Murakami), has analyzed mutations in the PKD1 gene associated with Polycystic Kidney Disease (PKD), a common hereditary kidney disease in cats, using pet insurance data and large-scale genetic testing data.

As a result, a comparison before and after the widespread adoption of comprehensive genetic testing for kittens revealed a 42.6% decrease in the proportion of cats with PKD1 gene mutations across all 14 breeds.

Furthermore, a significant decrease in the proportion of cats with the mutation was observed in Scottish Folds, Persians, and Ragamuffins. On the other hand, no clear increase in the degree of inbreeding was observed, suggesting that breeding management considering genetic diversity may have been implemented.

These research findings suggest that the spread of genetic testing is useful in reducing the risk of hereditary diseases in cats. This research was published online on June 18, 2026, in BMC Genomics, an international academic journal dealing with genome science published by Springer Nature.

Background of This Research

Polycystic Kidney Disease (PKD) (※1) is a hereditary disease in which numerous cysts form in the kidneys, leading to decreased kidney function and potentially renal failure as it progresses. It is particularly known in Persians and their related breeds, with specific mutations in the PKD1 gene (※2) being one of the primary causes. PKD can take time to develop, and affected cats may be used for breeding before clinical symptoms appear. Therefore, it has been difficult to fully assess the risk based solely on appearance or health status at a young age, making early confirmation through genetic testing and its application in breeding crucial.

In recent years, genetic mutations related to such hereditary diseases have become detectable through consumer genetic testing (※3). Particularly since the latter half of the 2010s, genetic testing, initially aimed at parent cats used for breeding, has become widely performed on kittens and is now utilized by many pet shops and breeders.

However, previous reports on feline PKD have often focused on individuals treated at secondary veterinary facilities such as university hospitals, leaving uncertainties regarding the prevalence in the general cat population and the frequency of gene mutations. Concerns have also been raised about increased inbreeding and reduced genetic diversity when individuals with causative mutations are excluded from breeding (※4).

Therefore, this study aimed to understand the overall picture of PKD, the relationship between the prevalence of PKD and PKD1 gene mutations, how their frequencies have actually changed, and whether these changes have impacted the genetic structure of the overall cat population, using pet insurance data and large-scale genetic testing data.

Research Results

1. Analysis of Cystic Kidney Disease Prevalence from Insurance Data

First, this study examined the prevalence of cystic kidney disease in 14 cat breeds using pet insurance claim data from Anicom General Insurance. Among 12,589 cats with insurance contracts of over 10 years, 21 cats were diagnosed with PKD or kidney cysts based on insurance claims. The median age at which the first claim for this disease was confirmed was 5 years, with no significant differences observed based on breed, sex, or age. Furthermore, in a group of 33,576 cats with genetic testing data regardless of insurance contract period, analysis linking insurance and genetic testing data revealed that 7 out of 9 cats (77.8%) diagnosed with cystic kidney disease carried the previously known PKD1 gene mutation. This indicates that, based on the analysis of insurance data in Japan, the PKD1 gene mutation is involved in a majority of feline PKD cases.

However, some cats diagnosed with cystic kidney disease did not possess the conventional PKD1 gene mutation. Therefore, by combining reference sequence data from AnAms1.0, previously developed by our company and recognized by Guinness World Records (Reference: Certified as Guinness World RecordTM for "World's Most Accurate Cat Genome Sequence"), with exome and whole-genome sequencing (※5) – proprietary technologies offered as testing services by our company – we searched for other candidate mutations in PKD-related genes. As a result, 8 new candidate mutations were identified in PKD-related genes, suggesting the involvement of genetic factors other than the conventional PKD1 mutation.

2. Analysis of PKD1 Mutation Frequency Changes from Genetic Testing Data of 61,968 Cats

Next, the frequency of PKD1 gene mutations was analyzed using genetic testing data from 61,968 cats across 14 breeds. The results showed breed-specific differences in the proportion of cats with PKD1 gene mutations as of 2022. Mutations were confirmed in breeds such as Himalayan, Persian, and Scottish Fold, while no cats with the conventional PKD1 mutation were found in the data for Ragdoll, Maine Coon, Bengal, and Russian Blue. Furthermore, a comparison between the periods before and after the widespread adoption of genetic testing for kittens revealed a 42.6% decrease in the proportion of cats with PKD1 gene mutations across all 14 breeds. Detailed analysis of 8 breeds with sufficient sample sizes showed a significant decrease in the proportion of cats with PKD1 gene mutations in Scottish Folds, Persians, and Ragamuffins. Specifically, a decrease rate of 38.8% was observed in Persians, and 49.5% in Scottish Folds (from 3.2% in 2019 to 1.6% in 2022).

3. Verification of the Relationship Between Gene Mutation Reduction and Inbreeding

In efforts to reduce mutations related to hereditary diseases, excluding individuals with mutations from breeding can lead to a decrease in the number of individuals used for breeding, potentially increasing inbreeding. Therefore, this study conducted population genetic analysis using whole-genome mutation data for Scottish Folds and Persians, where a decrease in PKD1 gene mutation frequency was confirmed.

The results showed no significant changes in the overall genetic structure of the population when comparing 2019 and 2022. Furthermore, no significant increase was observed in indicators of inbreeding. On the other hand, a notable decrease in effective population size (※6) – the estimated number of individuals contributing to actual reproduction – was observed in the population of cats with PKD1 gene mutations compared to those without. This suggests that cats with PKD1 gene mutations may have had reduced opportunities to be used in breeding, indicating progress in breeding management utilizing genetic testing.

Significance of This Research

This study revealed that PKD1 gene mutations related to feline PKD have decreased in some breeds with the spread of genetic testing. Particularly important is that while the reduction of PKD1 gene mutations was confirmed, no clear increase in the degree of inbreeding was observed in Scottish Folds and Persians. This suggests the possibility of balancing the reduction of hereditary disease risk with the improvement of animal welfare by utilizing genetic testing not merely to "exclude individuals with mutations," but also to incorporate it into breeding plans while considering genetic diversity. Previous research by the collaborative research team has yielded similar results for mutations related to hereditary diseases in Corgis and Miniature Dachshunds (Reference 1: Further progress towards eradicating the lethal hereditary disease "Degenerative Myelopathy (DM)" in dogs) (Reference 2: Widespread genetic testing significantly reduces the risk of "Progressive Retinal Atrophy (PRA)" in dogs).

On the other hand, a decrease in PKD1 gene mutations was not observed in some breeds, including British Shorthairs, Minuets, and Munchkins. Moving forward, it is important to promote the use of genetic testing in these breeds as well and to consider appropriate breeding management practices.

Future Prospects

This study reaffirmed that the conventional PKD1 gene mutation is significantly involved in feline PKD. However, the existence of cats diagnosed with cystic kidney disease despite not having the PKD1 gene mutation suggests the involvement of unknown genetic factors or factors difficult to detect with conventional single-gene testing.

Future research, including comprehensive genome analysis using next-generation sequencers and integrated analysis with larger-scale insurance and clinical data, is expected to elucidate the pathogenesis of feline PKD and other hereditary diseases.

【Original Paper Information】

Journal: BMC Genomics

Paper Link: https://link.springer.com/article/10.1186/s12864-026-13048-4

Original Title: Widespread genetic testing controls inherited polycystic kidney disease while avoiding inbreeding in cats

Authors: Hisashi Ukawa 1,2, Akane Kida 2, Kai Ataka 1, Ryo Horie 2,3, Yuki Matsumoto 1,2,3,4

1: Anicom Phar Inc., Testing Business Division

2: Anicom General Insurance Co., Ltd., R&D Department

3: Anicom Advanced Medical Research Institute Inc., Research and Development Department

4: Azabu University Data Science Center

【Glossary】

(※1) Polycystic Kidney Disease (PKD)

A hereditary disease in which numerous fluid-filled sacs (cysts) form in the kidneys. The cysts gradually enlarge, leading to decreased kidney function and, in severe cases, renal failure. In cats, it is particularly known to occur in Persians and their related breeds. Since affected cats may be used for breeding before symptoms appear, pre-confirmation through genetic testing is considered important.

(※2) PKD1 gene mutation: A mutation in the gene that is the primary cause of Polycystic Kidney Disease. Having just one copy of this mutation causes the disease (dominant inheritance). This mutation is responsible for the majority (approximately 80%) of feline PKD cases and can be confirmed in advance through genetic testing.

(※3) Consumer genetic testing: Genetic testing services that can be directly applied for by owners and breeders without going through a medical institution. By simply collecting and sending a sample, such as a swab from the oral mucosa, the presence or absence of risk mutations for hereditary diseases can be investigated.

(※4) Inbreeding: Mating between individuals with close blood relationships. As inbreeding progresses, genetic diversity is lost, increasing the risk of hereditary diseases and physical weaknesses becoming more apparent. In this study, the fact that an increase in inbreeding was not observed concurrently with the decrease in PKD1 mutations is a significant finding.

(※5) Exome sequencing / Whole-genome sequencing: Analytical methods that comprehensively read the base sequences of genes. Exome sequencing focuses on the protein-coding regions, while whole-genome sequencing targets the entire genome. These are used to search for the causes of cases that cannot be explained by known mutations. (Reference: Comprehensive genetic testing: NGS testing services)

(※6) Effective population size: A genetically estimated value of the number of individuals contributing to actual reproduction. It is an indicator of "how many individuals are involved in maintaining genetic diversity," rather than the absolute number of individuals. In this study, the decrease in effective population size of cats with PKD1 mutations suggests that cats with the mutation were used less frequently for breeding.