Methods of diagnosis of monogenic hereditary diseases
Until recently, the diagnosis of monogenic hereditary diseases based solely on the features of the phenotypic manifestations of the disease.Only under certain hereditary metabolic diseases diagnosis performed by determining the level of metabolites altered or modified enzyme.Phenotypic level diagnostics was sometimes enough to solve some problems of clinical genetics, for example, for a choice of tactics of treatment of clinically similar but genetically very heterogeneous disorders such as neuromuscular diseases or pigmentary retinal dystrophy.
should also highlight that treatment in these cases was purely symptomatic.Advances in molecular genetics allow for many monogenic diseases diagnostics translate to the level of determination of changes in the genotype.From the preceding chapters of the text should be clear that such a DNA diagnosis, in some cases, fundamentally changes the idea of the classification of hereditary diseases and opens new opportunities for pathogenetic treatment of hereditary di
All methods of DNA diagnostics of hereditary diseases can be divided into direct and indirect.Both direct and indirect methods of DNA diagnostics are very diverse.Direct methods of analysis have several advantages.For them, there is no need to examine other family members or to take into account the possible recombination in the gene.There is also the problem of lack of informativeness of genetic markers.
main indirect method the DNA diagnosis of hereditary diseases is the linkage analysis using as genetic markers to search for coupling with various disease gene DNA polymorphisms.Linkage analysis can be applied to any mapped gene hereditary disease.It does not require the study of the fine structure of the mutant gene.DNA markers allow to ascertain whether the individual has inherited the chromosome carrying the mutant gene or not.coupling method has several disadvantages, among them - the need to study a large number of relatives of the patient in order to determine with any marker alleles and how a gene linked diseases;the need to consider the possibility of crossover (cross) between DNA markers and the disease gene, which does not allow to be assured on 100% in the diagnosis of disease.This is achieved using direct methods.
Phenotypic features dealt with by medical genetics, is the hereditary diseases and their symptoms.Between the symptoms of hereditary diseases and the change of the protein as a result of mutations in any particular gene huge distance.The mutant protein product of the mutant gene must somehow communicate with hundreds, if not thousands of other proteins encoded by other genes, to change some characteristic or normal pathological symptom appeared.In addition, gene products involved in the development of any phenotypic trait may interact with environmental factors and their modified.
Monogenic inherited diseases are inherited according to the rules established by Mendel.There are autosomal dominant and autosomal recessive hereditary disease.Pedigrees of families in which the disease are inherited in this way, have a number of distinguishing characteristics.There are also strict methods of proof of a dominant or recessive inheritance disease.