Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic renal disorder caused by mutation in 2 genes PKD1 and PKD2. Thus far, no mutation is identified in approximately 10% of ADPKD families, which can suggest further locus heterogeneity. Owing to the complexity of direct mutation detection, linkage analysis can initially identify the responsible gene in appropriate affected families. Here, we evaluated an Iranian ADPKD family apparently unlinked to both PKD1 and PKD2 genes. This is one of the pioneer studies in genetic analysis of ADPKD in Iranian population.
Methods: Linkage reanalysis was performed by regenotyping of flanking microsatellite markers in 8 individuals of the ADPKD family. Direct mutation analysis was performed by Sanger sequencing.
Results: Mutation analysis revealed a pathogenic mutation (c.1094+1G>A) in the PKD2 gene in the proband. Analyzing 2 healthy and 4 clinically affected members confirmed the correct segregation of the mutation within the family and also ruled out the disease in 1 suspected individual. Misinterpretation of the linkage data was due to the occurrence of 1 crossing over between the PKD2 intragenic and the nearest downstream marker (D4S2929). Homozygosity of upstream markers caused the recombination indistinguishable.
Conclusion: Although analysis of additive informative polymorphic markers can overcome the misleading haplotype data, it is limited because of the lack of other highly polymorphic microsatellite markers closer to the gene. Direct mutation screening can identify the causative mutation in the apparently unlinked pedigree; moreover, it is the only approach to achieve the confirmed diagnosis in individuals with equivocal imaging results.
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http://dx.doi.org/10.1016/j.krcp.2016.02.003 | DOI Listing |
Proc Natl Acad Sci U S A
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Cancer Biology & Genetics Program, Sloan Kettering Institute, New York, NY 10065.
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Laboratory of Precision Medicine and Biopharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Recurrent missense mutations in the human epidermal growth factor receptor 2 (HER2) have been identified across various human cancers. Among these mutations, the active S310F mutation in the HER2 extracellular domain stands out as not only oncogenic but also confers resistance to pertuzumab, an antibody drug widely used in clinical cancer therapy, by impeding its binding. In this study, we have successfully employed computational-aided rational design to undertake directed evolution of pertuzumab, resulting in the creation of an evolved pertuzumab variant named Ptz-SA.
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January 2025
Division of Livestock Infectious Diseases, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.
Historically considered to be nonenveloped, hepatitis E virus (HEV), an important zoonotic pathogen, has recently been discovered to egress from infected cells as quasi-enveloped virions. These quasi-enveloped virions circulating in the blood are resistant to neutralizing antibodies, thereby facilitating the stealthy spread of infection. Despite abundant evidence of the essential role of the HEV-encoded ORF3 protein in quasi-enveloped virus formation, the underlying mechanism remains unclear.
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January 2025
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, United States of America.
Host-pathogen interactions represent a dynamic evolutionary process, wherein both hosts and pathogens continuously develop complex mechanisms to outmaneuver each other. Borrelia burgdorferi, the Lyme disease pathogen, has evolved an intricate antigenic variation mechanism to evade the host immune response, enabling its dissemination, persistence, and pathogenicity. Despite the discovery of this mechanism over two decades ago, the precise processes, genetic elements, and proteins involved in this system remain largely unknown.
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CSIRO Agriculture and Food, Canberra, ACT, 2601, Australia.
Zebularine-treated wheat uncovered a phenotype with characteristics of an epigenetically regulated trait, but major chromosomal aberrations, not DNA methylation changes, are the cause, making zebularine unsuitable for epigenetic breeding. Breeding to identify disease-resistant and climate-tolerant high-yielding wheats has led to yield increases over many years, but new hardy, higher yielding varieties are still needed to improve food security in the face of climate change. Traditional breeding to develop new cultivars of wheat is a lengthy process taking more than seven years from the initial cross to cultivar release.
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