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Resulting Phenotype (resulting + phenotype)
Selected AbstractsMolecular diagnosis of inherited disorders: lessons from hemoglobinopathies,HUMAN MUTATION, Issue 5 2005George P. Patrinos Abstract Hemoglobinopathies constitute a major health problem worldwide, with a high carrier frequency, particularly in certain regions where malaria has been endemic. These disorders are characterized by a vast clinical and hematological phenotypic heterogeneity. Over 1,200 different genetic alterations that affect the DNA sequence of the human ,-like (HBZ, HBA2, HBA1, and HBQ1) and ,-like (HBE1, HBG2, HBG1, HBD, and HBB) globin genes are mainly responsible for the observed clinical heterogeneity. These mutations, together with detailed information about the resulting phenotype, are documented in the globin locus-specific HbVar database. Family studies and comprehensive hematological analyses provide useful insights for accurately diagnosing thalassemia at the DNA level. For this purpose, numerous techniques can provide accurate, rapid, and cost-effective identification of the underlying genetic defect in affected individuals. The aim of this article is to review the diverse methodological and technical platforms available for the molecular diagnosis of inherited disorders, using thalassemia and hemoglobinopathies as a model. This article also attempts to shed light on issues closely related to thalassemia diagnostics, such as prenatal and preimplantation genetic diagnoses and genetic counseling, for better-quality disease management. Hum Mutat 26(5), 399,412, 2005. © 2005 Wiley-Liss, Inc. [source] Gene conversions are a common cause of von Willebrand diseaseBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2005P. K. Gupta Summary von Willebrand disease (VWD), the most common inherited bleeding disorder, is very heterogeneous, both in its phenotype and genotype. One particular molecular mechanism of VWD is due to recombination events between the true gene and its pseudogene on chromosome 22. We assessed the frequency and extension of such events in 50 multi-ethnic index patients with severe VWD type 3 and in five index patients with VWD type 2M Vicenza. One additional unclassified patient had been diagnosed with possible VWD in Russia solely on a clinical basis. Gene conversions, previously thought to be rare events, were identified in >10% of our study population: in six multi-ethnic patients with severe VWD type 3, in one patient with VWD type 2M Vicenza and the Russian patient was finally diagnosed with VWD type 2B New York/Malmoe. Our results suggest a significant contribution of this particular molecular mechanism to the manifestation of VWD. The location of the gene conversions, their extension and their occurrence as homozygous, compound heterozygous or heterozygous mutations determines the resulting phenotype. [source] Mutation analysis and characterization of COL7A1 mutations in dystrophic epidermolysis bullosaEXPERIMENTAL DERMATOLOGY, Issue 7 2008Ningning Dang Abstract:, Dystrophic epidermolysis bullosa (DEB) is inherited in both an autosomal dominant DEB and autosomal recessive manner RDEB, both of which result from mutations in the type VII collagen gene (COL7A1). To date, 324 pathogenic mutations have been detected within COL7A1 in different variants of DEB; many mutations are clustered in exon 73 (10.74%) which is close to the 39 amino acid interruption region. Dominant dystrophic epidermolysis bullosa usually involves glycine substitutions within the triple helix of COL7A1 although other missense mutations, deletions or splice-site mutations may underlie some cases. In recessive dystrophic epidermolysis bullosa, the mutations include nonsense, splice site, deletions or insertions, ,silent' glycine substitutions within the triple helix and non-glycine missense mutations within the triple helix or non-collagenous NC-2 domain. The nature of mutations in COL7A1 and their positions correlate reasonably logically with the severity of the resulting phenotypes. [source] Alternative parasite development in transmission strategies: how time flies!JOURNAL OF EVOLUTIONARY BIOLOGY, Issue 10 2010M. BADETS Abstract Among parasitic platyhelminths with complex life cycles, it has been well documented that transmission opportunities are the main forces shaping the diversity of life-history traits and parasite developmental strategies. While deviations in the development pathway usually involve shortening of life cycles, their extension may also occur following perception of remaining time by parasites. Polystoma gallieni, the monogenean parasite of Hyla meridionalis, is able to trigger two alternative developmental strategies depending on the physiological stage of the tadpoles upon which larvae attach. The distribution and reproductive outputs of both resulting phenotypes were surveyed to address questions about the dynamics of transmission in natural environments. Because modifications in the completion of life cycles can have drawbacks which may perturb the dynamic equilibrium of the resulting host,parasite systems, experimental infestations were also performed to assess parasite,parasite interactions. Our results suggest that the bladder adult phenotype, which involves transmission between frogs and tadpoles, is supplied secondarily by the branchial phenotype which involves transmission between tadpoles and metamorphs. They also support the occurrence of finely tuned trade-offs between hosts and parasites and highlight positive trends behind the extension of direct life cycles, in which host-derived signals account for the remaining time to achieve parasitic transmission. [source] | |||||||||||||