Article
Biotechnology & Applied Microbiology
Vanessa A. Raphtis, Dhruv Sharma, Sichao Wang, Jae Y. Kim, Amanda L. Jacobson, Christine D. Harman, Andras M. Komaromy
Summary: This study revealed a possible relationship between the G661R missense mutation in the ADAMTS10 gene and ocular pulse amplitude (OPA) in a canine model of open-angle glaucoma. Dogs with the mutation displayed higher intraocular pressure (IOP) and lower OPA compared to normal dogs. The findings suggest that OPA may be a valuable clinical tool for assessing ocular stiffness and susceptibility to elevated IOP.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Cell Biology
Menghan Xu, Jin Yang, Jiayue Sun, Xuemei Xing, Zheng Liu, Tao Liu
Summary: A novel heterozygous missense mutation c.977C>T in the PCK2 gene was identified in a five-generation Chinese PACG family, but not in unaffected individuals or unrelated healthy individuals. In vitro assays showed that the mutation induced cell cycle arrest and apoptosis in RGC-5 cells, with alterations in various signaling pathways.
Article
Ophthalmology
Hang-Jing Wu, Douglas P. Mortlock, Rachel W. Kuchtey, John Kuchtey
Summary: The study demonstrated that Adamts10(G661R/G661R) mice recapitulate the short stature and ocular phenotypes of WMS. The altered fibrillin-1 and fibrillin-2 immunoactivity in the mutant mice suggests that the G661R mutation of Adamts10 perturbs regulation of the fibrillin isotype composition of microfibrils in the mouse eye.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Medical Laboratory Technology
Li Li, Nan Zuo, Danyang Yang, Dingwei Zhang, Yiguo Feng, Xiaoli Li
Summary: DSAP, the most common clinical subtype of porokeratosis, was studied for gene mutations in four pedigrees and three sporadic cases in the Chinese population. Two gene mutations related to DSAP were identified, providing potential value for genetic counseling and prenatal diagnosis.
CLINICA CHIMICA ACTA
(2021)
Article
Biochemistry & Molecular Biology
Lucia Fadiga, Mariana Lavrador, Nuno Vicente, Luisa Barros, Catarina Goncalves, Asma Al-Naama, Luis R. Saraiva, Manuel C. Lemos
Summary: A novel missense mutation in the FGFR1 gene associated with CHH has been identified, expanding the mutational spectrum of this gene and contributing to the understanding of the pathogenesis of CHH.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Antonino Musumeci, Francesco Cali, Carmela Scuderi, Mirella Vinci, Girolamo Aurelio Vitello, Sebastiano Antonino Musumeci, Valeria Chiavetta, Concetta Federico, Greta Amore, Salvatore Saccone, Gabriella Di Rosa, Antonio Gennaro Nicotera
Summary: Recessive mutations in the POLR3A gene are associated with POLR3-HLD and deficient cerebral myelin formation. In a cohort of five families from Sicily, Italy, two cases of POLR3-related leukodystrophy were detected, with one caused by a compound heterozygous mutation in the POLR3A gene.
Article
Veterinary Sciences
Richard A. A. Pytak, Christopher G. G. Pirie, Christine D. D. Harman, Amanda L. L. Anderson, Shay Xuejing Yao, Andras M. Komaromy
Summary: This study aimed to evaluate the anterior segment angiographic findings in hypertensive ADAMTS10-open-angle glaucoma (ADAMTS10-OAG) eyes compared to normotensive control eyes. The results showed that the time to onset of all angiographic phases was significantly prolonged, while the time to onset of sodium fluorescein (SF) leakage into the aqueous humor was significantly reduced in glaucomatous eyes. Only glaucomatous eyes demonstrated evidence of SF stromal leakage. Multiple linear regression analysis indicated that glaucoma was not predictive of the time to onset of any angiographic phase or leakage, but pulse was a significant factor contributing to the severity of aqueous humor leakage.
VETERINARY OPHTHALMOLOGY
(2023)
Article
Genetics & Heredity
Runfeng Zhang, Peng Jia, Yanyi Yao, Feng Zhu
Summary: This study reported a case of mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH) in a Chinese family. Through genetic analysis, a novel variant in the CASK gene associated with the disease was identified. The patient exhibited symptoms such as microcephaly, pontocerebellar hypoplasia, and severe intellectual disabilities. This research facilitates the diagnosis of the disease in the family and expands the variant spectrum of the CASK gene in MICPCH patients.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Yuting Zeng, Yuhua Pan, Jiayao Mo, Zhiting Ling, Lifang Jiang, Fu Xiong, Wenjuan Yan
Summary: A missense mutation in the COL1A1 gene was found to cause a DGI-I phenotype without bone disease, with ultrastructural analysis revealing severe developmental disorder. The use of patient DPSCs for research can help elucidate pathogenesis and develop regenerative therapies.
FRONTIERS IN GENETICS
(2021)
Article
Cell Biology
Wei Jiang, Mengyue Deng, Chun Gan, Li Wang, Huawei Mao, Qiu Li
Summary: A novel TNFAIP3 variation (c.1804A > T, p.T602S) related to Behcet-like disease was reported, causing over-activation of the canonical NF-KB signaling pathway in patient PBMCs. The identified mutation triggers a dominantly inherited Behcet-like disorder due to A20 haploinsufficiency, emphasizing the importance of prenatal diagnosis and therapeutic intervention.
CELLULAR IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yanbo Kong, Haoan Yi, Fan Li, Xiu Duan, Lipu Yang, Xinyu Fan, Guojiu Wu, Minjun Ma, Xu Zha, Yongshu He
Summary: The aim of this study was to identify the causative gene associated with presenile cataract in a Chinese family. Through pedigree analysis and genetic sequencing, a mutation in the CRYBA2 gene was found to potentially contribute to the development of the disease.
MOLECULAR GENETICS AND GENOMICS
(2023)
Article
Genetics & Heredity
Ang Li, Siwen Liu, Peng Zhang, Xintong Hu, Guiying Li, Weiyue Gu, Yanfang Jiang
Summary: This study identified a novel mutation in the SIX1 gene that is associated with NS-UHL in a three-generation Chinese family. Bioinformatics analysis confirmed the pathogenicity of this mutation and its impact on the structure of the SIX1 protein.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Shafaq Ramzan, Stephanie Tennstedt, Muhammad Tariq, Sheraz Khan, Hafiza Noor Ul Ayan, Aamir Ali, Matthias Munz, Holger Thiele, Asad Aslam Korejo, Abdul Razzaq Mughal, Syed Zahid Jamal, Peter Nuernberg, Shahid Mahmood Baig, Jeanette Erdmann, Ilyas Ahmad
Summary: The study investigated a consanguineous Pakistani family with four patients with cardiac conduction disease and identified a novel homozygous missense mutation in the TNNI3K gene. Molecular dynamics simulations showed changes in protein surface and hydrogen bond network due to the mutation. Analysis revealed structural variations in the ATP-binding pocket and homodimer interface caused by the mutation, suggesting it as a pathogenic variant.
Article
Genetics & Heredity
Lu Cao, Ruixue Zhang, Liang Yong, Shirui Chen, Hui Zhang, Weiwei Chen, Qiongqiong Xu, Huiyao Ge, Yiwen Mao, Qi Zhen, Yafen Yu, Xia Hu, Liangdan Sun
Summary: A novel missense mutation in the SASH1 gene was identified as the cause of Dyschromatosis universalis hereditaria (DUH) in a Chinese family. Despite the affected family members having identical mutations, differences in clinical manifestations were observed, highlighting the complexity of phenotype-influencing factors in DUH.
BMC MEDICAL GENOMICS
(2021)
Article
Genetics & Heredity
Xuefeng Xie, Mazhar Khan, Muhammad Zubair, Abbas Khan, Ranjha Khan, Jianteng Zhou, Yuanwei Zhang, Muzafar Said, Sher Ali Khan, Qamar Zaman, Ghulam Murtaza, Muzamil Ahmad Khan, Wei Liu, Xiaoning Hou, Huan Zhang, Bo Xu, Xiaohua Jiang, Shun Bai, Qinghua Shi
Summary: Non-obstructive azoospermia (NOA) is a major cause of male infertility, with the majority of cases remaining idiopathic. This study identified a novel missense mutation in the DND1 gene using whole-exome sequencing, and demonstrated its impact on male fertility through protein misfolding and weakened interaction with the crucial regulator NANOS2 in primordial germ cell development.
FRONTIERS IN GENETICS
(2022)
Article
Agriculture, Dairy & Animal Science
Christopher A. Jenkins, Ellen C. Schofield, Cathryn S. Mellersh, Luisa De Risio, Sally L. Ricketts
Summary: Genotype imputation using a reference panel combining high-density array data with publicly available whole genome sequence consortium variant data is shown to be an effective and accurate method to increase the density of lower-density array datasets in dogs. The study demonstrates high accuracy in imputation, utilizing reference panels consisting of breed-specific array data and multi-breed variant data. The findings provide evidence and support for the efficacy of this approach in canine genetics.
Article
Clinical Neurology
Silvia Nitschke, Mitchell A. Sullivan, Sharmistha Mitra, Charlotte R. Marchioni, Jennifer P. Y. Lee, Brandon H. Smith, Saija Ahonen, Jun Wu, Erin E. Chown, Peixiang Wang, Sara Petkovic, Xiaochu Zhao, Laura F. DiGiovanni, Ami M. Perri, Lori Israelian, Tamar R. Grossman, Holly Kordasiewicz, Francisco Vilaplana, Kazuhiro Iwai, Felix Nitschke, Berge A. Minassian
Summary: This study investigates the influence of glucan chain length on precipitation and the disease caused by abnormal glycogen structure. The authors found that the glycogen pathology of RBCK1 deficiency is similar to malin-deficient Lafora disease and can be rescued by downregulating glycogen synthase.
Article
Veterinary Sciences
Hannah K. Walker, Claudia Ottka, Hannes Lohi, Ian Handel, Dylan N. Clements, Adam G. Gow, Richard J. Mellanby
Summary: The study found no clear evidence supporting the need to establish seasonal reference ranges for serum metabolites in dogs, as only a few metabolites showed statistically significant seasonal variance.
JOURNAL OF VETERINARY INTERNAL MEDICINE
(2022)
Article
Psychiatry
Milla Salonen, Salla Mikkola, Emma Hakanen, Sini Sulkama, Jenni Puurunen, Hannes Lohi
Summary: This study examined the associations between personality traits and unwanted behavioral traits in dogs. The results showed that dog personality traits resemble human personality traits and are associated with similar patterns of unwanted behaviors. This suggests that dogs may be a suitable animal model for studying human behavior and psychiatric disorders.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Multidisciplinary Sciences
Jenni Puurunen, Claudia Ottka, Milla Salonen, Julia E. Niskanen, Hannes Lohi
Summary: Metabolomics has vast potential in biomedical applications. Factors such as age, breed, sex, sterilization, diet type, and fasting time significantly affect the metabolite profiles of healthy pet dogs, with breed and age causing considerable variation in metabolite concentrations.
ROYAL SOCIETY OPEN SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Carolin Anna Imbery, Frank Dieterle, Claudia Ottka, Corinna Weber, Gotz Schlotterbeck, Elisabeth Mueller, Hannes Lohi, Urs Giger
Summary: The adrenal glands play a major role in metabolic processes, and abnormal serum cortisol concentrations can have serious metabolic consequences. Analysis of serum samples from untreated and treated hyperadrenocorticism and hypoadrenocorticism in dogs revealed metabolic abnormalities that tended to normalize with treatment, but not completely.
Article
Genetics & Heredity
Janelle M. Belanger, Tiina Heinonen, Thomas R. Famula, Paul J. J. Mandigers, Peter A. Leegwater, Marjo K. Hytonen, Hannes Lohi, Anita M. Oberbauer
Summary: A risk haplotype on CFA14 was found to interact with a common risk haplotype on CFA37 in Belgian shepherds, increasing the risk of idiopathic epilepsy. The ACTG haplotype on CFA14 and GG haplotype on CFA37 were associated with elevated risk, and a disruptive insertion in the RAPGEF5 gene adjacent to CFA14 haplotype was identified.
Article
Genetics & Heredity
Maria Kaukonen, Michelle E. McClements, Robert E. MacLaren
Summary: Retinitis pigmentosa (RP) is a common inherited retinal degenerative disease, and pathogenic variants in the Rhodopsin (RHO) gene are the main cause of autosomal dominant RP (adRP). Base editing technology provides exciting possibilities for treating adRP, but further research is needed for optimization.
Article
Multidisciplinary Sciences
Salla Mikkola, Milla Salonen, Emma Hakenan, Hannes Lohi
Summary: Problematic behavior is a significant welfare issue in cats and a common reason for relinquishment. Fearfulness, aggression towards humans, and excessive grooming are comorbid with each other, and breed and environmental variables are associated with these behaviors. Poor socialization with humans and a history of being a rescue cat are linked to higher fearfulness.
Article
Genetics & Heredity
Maram E. A. Abdalla Elsayed, Maria Kaukonen, Peter Kiraly, Jasmina Cehajic Kapetanovic, Robert E. E. MacLaren
Summary: In this study, bioinformatic analysis was used to explore potential therapeutic options for a patient with Sorsby fundus dystrophy. Genetic testing revealed a TIMP3 variant, which could be corrected using gene editing technology.
Article
Genetics & Heredity
Tiina Heinonen, Thomas Flegel, Hanna Mueller, Alexandra Kehl, Sruthi Hundi, Kaspar Matiasek, Andrea Fischer, Jonas Donner, Oliver P. Forman, Hannes Lohi, Marjo K. Hytoenen
Summary: In this study, a Miniature Australian Shepherd family with symptoms similar to hereditary hyperekplexia in humans was reported. Whole genome sequence data analysis revealed a 36-bp deletion in the GLRA1 gene, which was found to be completely associated with the disease in pedigree samples and additional cohorts of related dog breeds. This study establishes a spontaneous large animal disease model for human hereditary hyperekplexia by associating a variant in the canine GLRA1 gene with the disorder for the first time.
Article
Multidisciplinary Sciences
Hanna Sinkko, Jenni Lehtimaki, Hannes Lohi, Lasse Ruokolainen, Anna Hielm-Bjorkman
Summary: The rising trend in non-communicable chronic inflammatory diseases coincides with changes in Western lifestyle. While changes in the human microbiota may play a central role in the development of chronic diseases, estimating the contribution of associated lifestyle factors remains challenging. We studied the influence of lifestyle factors, such as diet, antibiotic use, and residential environment, on the gut microbiota of healthy and atopic pet dogs. The results showed that diet was the most significant factor associated with gut microbiota, while antibiotic use was associated with the severity of symptoms in atopic dogs.
ROYAL SOCIETY OPEN SCIENCE
(2023)
Article
Agriculture, Dairy & Animal Science
Marjo K. K. Hytonen, Sanna Viitanen, Sruthi Hundi, Jonas Donner, Hannes Lohi, Maria Kaukonen
Summary: This study confirmed the presence of hemophilia A in two Labrador Retriever pedigrees and identified a mutation associated with it through whole-genome sequencing. A gene test can now be developed to screen dogs before breeding to prevent further cases. However, the cause of decreased FVIII activity in another affected dog remains to be determined in future studies.
Article
Genetics & Heredity
Soma Farag, Imran H. Yusuf, Maria Kaukonen, Laura J. Taylor, Peter Charbel Issa, Robert E. Maclaren
Summary: CDHR1-associated RP exhibits a relative preservation of cone function in the presence of a presumed hypomorphic allele and may be considered a hypomorphic disease phenotype. Further research is needed to identify modifying factors that determine disease phenotype, as macular dystrophy with relative sparing of rods may also occur with hypomorphic CDHR1 alleles.
OPHTHALMIC GENETICS
(2023)
Article
Genetics & Heredity
Julia E. Niskanen, Asa Ohlsson, Ingrid Ljungvall, Michaela Droegemueller, Robert F. Ernst, Dennis Dooijes, Hanneke W. M. van Deutekom, J. Peter van Tintelen, Christian J. B. Snijders Blok, Marion van Vugt, Jessica van Setten, Folkert W. Asselbergs, Aleksandra Domanjko Petric, Milla Salonen, Sruthi Hundi, Matthias Hoertenhuber, DoGA Consortium, Juha Kere, W. Glen Pyle, Jonas Donner, Alex V. Postma, Tosso Leeb, Goran Andersson, Marjo K. Hytonen, Jens Haggstrom, Maria Wiberg, Jana Friederich, Jenny Eberhard, Magdalena Harakalova, Frank G. van Steenbeek, Gerhard Wess, Hannes Lohi
Summary: This study used a canine model of dilated cardiomyopathy (DCM) to perform genome-wide analysis and identified two novel candidate genes associated with DCM. It also revealed the complex genetic factors involved in the disease, including cardiac function, energy homeostasis, and morphology. Additionally, the study found candidate variants in these two genes in human DCM patients.