神经生物学

Single-strand conformational polymorphism (SSCP) analysis is a technique used to screen for the presence of sequence variations in short DNA fragments. This technique relies on the ability of single-stranded DNA molecules to fold into unique secondary structures, the conformati ...

Tay-Sachs disease is a severe, neurodegenerative disease fatal in childhood that is caused by deficiency of the enzyme β-hexosaminidase A (Hex A) (1). Tay-Sachs is most common in the Ashkenazi Jewish population, with an incidence of 1/3600 affected individuals and a carrier rate of approx 1 in 30 (1). ...

The detection of abnormal variations in a DNA sequence is a challenge for genetic research and clinical diagnostic applications. Among the different mutation detection methods currently available, DNA sequence analysis is largely considered the gold standard because it provides ...

Classic galactosemia is an autosomal recessive disorder caused by the deficiency of galactose 1-phosphate uridyltransferase, GALT (EC 2.7.7.12) (1). It presents with vomiting and diarrhea in neonates within a few days of milk intake. Most patients develop jaundice and hepatic failure. If ...

A conventional method used for DNA size measurement is gel electrophoresis. In this process, an electric field is applied to a gel medium and DNA molecules are separated by size. However, this process is slow and takes hours to separate different sizes of DNA fragments. Other physical and chemical p ...

Polyglutamine (polygln) expansion in specific proteins is one of the most intriguing pathogenic mechanisms causing adult-onset neurodegenerative disorders. In all the cases studied so far, the normal gene products tolerate a rather wide variation in size of a polygln tract (ranging t ...

Expansions of unstable CAG/CTG trinucleotide repeats have been identified as a common pathogenic mechanism in a growing number of hereditary neurodegenerative diseases, including myotonic dystrophy, spinal and bulbar muscular atrophy, Huntington’s disease (HD), spinoce ...

Microsatellite repeat expansions have been shown to cause a number of neurodegenerative diseases (1). Most of the disease genes identified to date involve the expansion of a trinucleotide repeat motif, but recently tetra- and pentanucleotide repeat expansions have been shown to cause m ...

Trinucleotide repeat sequences are present at approx 30,000-40,000 loci in the human genome (1). The majority of these repeats are below 35 copies and are stably transmitted. However, unstable trinucleotide repeat expansions at some loci have been found to be the causal mutation for nearly 20 g ...

The autosomal dominant cerebellar ataxias are each defined by progressive ataxia and variable association with other clinical findings (1). Numerous spinocerebellar ataxia (SCA) loci have been identified and several of the SCA genes have expansion of a CAG-repeat as the underlying mu ...

The expansion of trinucleotide CAG repeat sequences has been shown to be the underlying cause of eight human neurodegenerative disorders, including Huntington’ s disease (HD), spinal and bulbar muscular atrophy (SBMA), dentatorubral-pallidoluysian atrophy (DRPLA), Machado- ...

The use of recombinant DNA technology to clone, sequence, and express ion channels and transporters has powered an enormous acceleration in the understanding of structure-function relationships in these important proteins. Given that most ion channels reside in tissues that are lar ...

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder resulting from expansion (37 units) of a polyglutamine tract in huntingtin, a 350 kDa protein of unknown function (1). The N-terminal region of huntingtin contains the glutamine repeat, which is encoded by ex ...

The muscular dystrophies are a genetically heterogeneous group of disorders characterized by progressive wasting, weakness, and degeneration of the skeletal muscle. The types of muscular dystrophy have been classified according to clinical symptoms, disease progression, i ...

The fruit fly, Drosophila melanogaster, has been used extensively as an experimental model organism since the beginning of the last century. More recently, the concept of large-scale genetic mutagenesis screens has been applied. In the first such screen, 15 loci spread throughout the geno ...

Despite many shortcomings, a reductionist approach using cell culture paradigms to define basic principles underlying disease processes has considerable merit. One example of the utility of this approach is the expression of mutant forms of proteolipid protein 1 (PLP1) in transien ...

The development of molecular probes by using DNA sequences of differing sizes, complexity, and specificity, coupled with technological innovations such as multicolor fluorochromes, computerized signal amplification, and image analysis, makes fluorescent in situ hybridi ...

Imprinting is the naturally occurring functional inequality of alleles of a given gene reflecting their parental origin. Only one of the alleles (either maternal or paternal) is functional (producing mRNA) in an imprinted gene. Imprinted genes in the human genome have been identified and a ...

Over a century ago, the two French neurologists Charcot and Marie and the English neurologist Tooth described a peripheral neuropathy. They had defined a clinical entity, which is now known as Charcot-Marie-Tooth disease (CMT) or hereditary motor and sensory neuropathy (HMSN). Neuropat ...

Animal models of disease in genetically manipulated mice are powerful tools in medical research, including the study of dementia. The time and expense required to make genetically altered mice is considerable, and the importance of this investment is amplified by the long time course of most ...