Adv Genet
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The reproductive biology of Drosophila melanogaster is described and critically discussed, primarily with regard to genetic studies of sex-specific behavior and its neural underpinnings. The investigatory history of this system includes, in addition to a host of recent neurobiological analyses of reproductive phenotypes, studies of mating as well as the behaviors leading up to that event. Courtship and mating have been delved into mostly with regard to male-specific behavior and biology, although a small number of studies has also pointed to the neural substrates of female reproduction. ⋯ This matter is mentioned because--in conjunction with the contemporary broadening and deepening of this investigatory area--brief summaries of its findings are appearing with increasing frequency. This chapter will, from time to time, present our opinion that a fair fraction of the recent minireviews are replete with too many catch phrases about what is really known. This is one reason why the treatment that follows not only attempts to describe the pertinent primary reports in detail but also pauses often to discuss our views about current understandings of sex-specific behavior in Drosophila and its underlying biology.
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SCN9A, the gene which encodes voltage-gated sodium channel Na(v)1.7, is located on human chromosome 2 within a cluster of other members of this gene family. Na(v)1.7 is present at high levels in most peripheral nociceptive neurons in dorsal root ganglion (DRG) and in sympathetic neurons. In addition to its focal tissue-specific expression, Na(v)1.7 is distinguished by its ability to amplify small depolarizations, thus acting as a threshold channel and modulating excitability. ⋯ Mutant Na(v)1.7 channels lower the threshold for single action potentials and increase the number of action potentials that neurons fire in response to suprathreshold stimuli. In contrast, recessively inherited loss-of-function mutations in SCN9A, which cause a loss of function of Na(v)1.7 in patients, lead to indifference to pain with sparing of motor and cognitive abilities. The central role of Na(v)1.7 in these disorders, and the apparently limited consequences of loss of this channel in humans make it an attractive target for treatment of pain.
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Migraine is a severely debilitating episodic disorder affecting up to 12% of the general population. Migraine arises from both genetic and environmental factors, complicating our understanding of what makes the migraine brain susceptible to attacks. In recent years, powerful genetic screening tools have revealed several single genes linked to migraine. ⋯ In addition, the identification of monogenic subtypes has made it possible to generate suitable animal models for migraine. The purpose of this review is to present an overview of the clinical features of migraine and discuss the continuing highway of migraine gene discovery. The genes associated with FHM will be discussed, including what we have learned from studying the functional consequences of FHM mutations in cellular and animal models.
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Myotonia is a symptom of many different acquired and genetic muscular conditions that impair the relaxation phase of muscular contraction. Myotonia congenita is a specific inherited disorder of muscle membrane hyperexcitability caused by reduced sarcolemmal chloride conductance due to mutations in CLCN1, the gene coding for the main skeletal muscle chloride channel ClC-1. The disorder may be transmitted as either an autosomal-dominant or recessive trait with close to 130 currently known mutations. Although this is a rare disorder, elucidation of the pathophysiology underlying myotonia congenita established the importance of sarcolemmal chloride conductance in the control of muscle excitability and demonstrated the first example of human disease associated with the ClC family of chloride transporting proteins.