| Background and Purpose Human genome project(HGP) includes two main parts: one is the sequencing of approximately 3 billion base pairs of human genome, and genotyping all genes to the chromosome, another is the functional genomics research. Genotyping and location of genes associated with the hereditary diseases are the main part of HGP. The investigation of candidate gene of diseases is important and valuable, not only to the diagnosis and differentiation, but also to the causes and pathogenesis of the diseases. The knowledge of genetic contributions to human disease will dramatically accelerate the development of new strategies for the diagnosis, prevention and treatment of disease, not just for single-gene disorders but for the host of more common complex diseases (e.g., diabetes, heart disease, schizophrenia, and cancer) for which genetic differences may contribute to the risk of contracting the disease and the response to particular therapies.Amyotrophic lateral sclerosis(ALS) is a specific form of motor neuron disease in which there are both upper and lower motor neuron signs. It is a progressive neurodegenerative disorder with a prevalence estimated as 3~5/100,000 in most areas of the world. The disease affects motor neurons in the anterior horn of the spinal cord, the motor nuclei of the brainstem and the pyramidal cells of the motor cortex, and is relentlessly progressive with most patients dying of ball paralysis or pulmonary infection within five years of clinical onset. Except in the condition that a few approved treatments prolong survival in ALS patients to some extent, no strategies used now can prevent the occurrence or interrupt the natural course of the disease. It has been found that ALS and other neurodegenerative disorders including Parkinson's disease, Huntington's disease, Alzheimer's disease and spinocerebellar ataxia have similar pathological menifestations, in which all lossed cells are dying of apoptosis and insoluble protein aggregation is found in the inclusions in the dying neurons and astrocytes. Investigating one of these diseases thoroughly may provide evidences for the pathogenesis of these diseases and may be helpful to develop the rational strategies for minimizing or preventing the diseases. Though familial ALS(FALS) only accounts for 10%-20% of ALS, it serves as anexcellent model for identifying an underlying gene defect responsible for motor neuron degeneration, for it has indistinguishable clinical and pathological expressions with sporadic ALS(SALS). It is believed that unraveling the molecular basis by which those mutant gene products cause neurodegeneration may shed light on the pathogenesis of the common sporadic form of ALS. Cytolic CuZn superoxide dismutase(SOD1) is the most important line of antioxidant enzyme defence system against reactive oxygen species(ROS), particularly superoxide anion radicals. It has reported that mutations in the gene of SOD1 are responsible for 20 % of cases of FALS. To date, more than 100 different heterozygous mutations in SOD1 have been found in patients with ALS, and all but one is dominant. Many of these mutations lead to the substitution of an amino acid within regions of the enzyme with very distinct structure and functional roles. It is thus fascinating to note that so many discrete SOD1 alternations share a similar clinical phenotype and the fact that SOD1 mutations, which are present at birth and, by virtue of SOD1's ubiquitous expression, in all tissues, produce a rapidly progressive adult-onset degenerative condition in which motor neurons are almost exclusively affected.Several other sites have been verified to associate to FALS. Another autosomal dominant form of ALS progresses slowly and begins before age of 25 years, the gene has been mapped to chromosome 9q34. The gene for ALS woth frontotemporal dementia had been mapped to 9q21-22. Autosomal recessive juvenile-onset ALS has been linked to chromosomes 2q33 and 15q15-22.There is no report on the genetic research of FALS in China. We have found an ALS...
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