Introduction:
Genetic factors include the genes, which are chemical constituents of the human body and are inherited by the parents and non-genetic factors include the environmental influences on the characteristics and behavior of an individual. Genetic variations that take place in an individual have a typical hereditary pattern. These hereditary patterns are divided into two types, namely:
-
Monogenic diseases.
-
Polygenic diseases.
Monogenic diseases include a group of genetic disorders that are caused due to alteration in the DNA (deoxyribonucleic acid) of a single gene, and polygenic disorders include disorders caused due to combined mutations in several genes present in different chromosomes. These disorders then get inherited by autosomal or sex-linked types of inheritance patterns. Cases of individual monogenic disorders are very rare, but when noted in combination or together with other monogenic disorders, it affects a large number of the population. These disorders are noted to be associated with a specific protein deficiency. Sickle cell anemia, cystic fibrosis, and Huntington's disease are a few commonly reported monogenic disorders.
What Is the Cause of Sickle Cell Anemia?
Sickle cell anemia is a genetic disorder that belongs to the category of monogenic disorders.
It is caused due to point mutation (a single nucleotide base is affected; the nucleotide base either gets deleted or inserted in the DNA of a given genomic sequence). The genetic variation results in the formation of hemoglobin S, which is rigid and sickle-shaped. It shows an autosomal recessive pattern of inheritance. Both the parents, the mother and the father of the individual affected by sickle cell anemia, carry the defective genes. Still, the parents do not show the symptoms of the disease. Genetic mutations (structural changes in the genes) are associated with sickle cell anemia. There is a twenty-five percent chance or probability that parents who are carriers of the defective gene will have children with sickle cell anemia. Genetic mapping in the prenatal stage can help doctors analyze the likelihood of the child suffering from sickle cell anemia.
How Do Characteristics Get Inherited?
A child inherits genes from both father and mother both. These genes code for traits (like hair color, height, etc.). Genes that code for traits from the parents are of two types, the first dominant and the other recessive. In the Indian subcontinent, black hair color is the dominant trait. So, for example, a gene for the father with black hair could be coded as BB (dominant) or BB (codes for black color), and genes for the mother with brown hair will be coded as BB (recessive). Now, the following could be the probable hair color of the child depending on the combination of the gene the child inherits:
-
BB - (black) 25 percent of the children.
-
BB - (black) 50 percent of the children.
-
BB - (brown) 25 percent of the children.
So, the ratio between black and brown hair color is 3:1; hence 25 percent of the children born could have brown hair. The above description states the inheritance pattern of general human characteristics. Similarly, if there is a genetic mutation, as in cases of monogenic disorders, the varied genetic characteristics get inherited following the same pattern as mentioned in the example above.
What Is the Role of Gene Mapping in Monogenic Disorder Diagnosis?
Genome mapping involves the identification of the chromosome that is causing a genetic variation; this is followed by physical maps in which the order of the DNA bases (DNA sequence) related to a particular behavior in the human population is marked on the chromosome. DNA markers (DNA sequences whose location on the chromosome is already known) mark the particular DNA sequence on a chromosome. The following are the outcomes of the human genome project:
-
Identification of disease-causing genes.
-
Introduction of molecular medicine.
-
Identification of genomic sequences in various types of cancer.
-
Advancement of forensic science.
GenBank database stores the DNA sequences of more than three lakh organisms. It helps genetic researchers get updated information about a particular genomic sequence. The United States National Center maintains it for biotechnology information and other associated centers in Europe and Japan. When a DNA sequence is searched in the Genbank database, it is described under the following headings:
-
Description of the searched DNA sequence.
-
Scientific names are given to every genomic sequence (it is a binomial name wherein the first name describes the genus and the second name describes the species).
-
Taxonomy (the scientific branch that categorizes organisms) of the source organism.
-
Bibliographical reference.
-
Table of features.
What Is the Role of Genetic Markers in Monogenic Disorder Diagnosis?
Genetic markers are DNA sequences whose location on the chromosome is already known to the researcher and is used for locating the gene of similar characteristics. Markers are made up of DNA fragments in which the gene is not present. Markers possess a unique ability to identify the disease-causing gene and thus help trace the inheritance of a particular characteristic from parents to offspring, generation after generation. Advancements in gene mapping procedures can form an easily understandable gene map, and genetic markers play an essential role in generating a valuable gene map. It took years to identify a particular gene causing the disease, but now it can be placed within weeks. This technique will help the researcher in studying the probability of the future generation getting affected by the genetic mutation associated with monogenic disorders.
What Protocols Should Be Followed for Improving Monogenic Disorder Management?
Following are the few points that are presently being noted while carrying out studies related to the management of monogenic disorders:
-
Multiple testing, along with carrying out studies in various population groups. This will enable the researcher to better understand the outcomes of the study.
-
Replicating studies in various population groups stratified based on age, sex, joint symptoms, and other associated factors will reduce false positive association results.
-
Researchers have started including populations from different races and ethnic backgrounds.
These considerations have helped researchers identify well-associated genes with monogenic disorders.
Conclusion:
Inheritance determines the individual's characteristics, and DNA's ability to mutate is a platform for human evolution. Various researchers are currently studying the inheritance pattern, and this research work also focuses on locating the genes that help identify the cause of a particular disease. Genetic mapping is the latest advancement in the field of medical genetics.
