Effect of Genetic Disorders – Disease and Causes

Mutation 

Mutation is the change in a gene or a chromosome that causes a change in a phenotypic character. 

Mutation is caused either by loss or gain or change in a single base pair of DNA 

• In addition to recombination, the mutation is another phenomenon that leads to variation in DNA. 
• Loss (deletion) or gain (insertion/duplication) of a segment of DNA results in alteration in chromosomes. 
• Chromosomal aberrations are observed in cancerous cells. 
• Mutations also arise due to change in a single base pair of DNA. This is known as a point mutation. E.g., Sickle cell anemia. 
• Deletion and insertions of base pairs of DNA cause frame shift mutations. 

Pedigree Analysis 

The representation or chart showing family history is called pedigree analysis  

• In the pedigree analysis, the inheritance of a particular trait is represented in the family tree over generations. 

In human genetics, the pedigree study is utilized to trace the inheritance of a specific trait, abnormality or disease. Some of the important standard symbols used in the pedigree analysis are shown in fig. no. 1.  

Mendelian Disorders 

• Broadly, genetic disorders may be grouped into two categories – Mendelian disorders and chromosomal disorders.  

Mendelian disorders are caused by alteration or mutation in a single gene.  

• These disorders are transmitted to the offspring on the same lines as we studied in the principle of inheritance.  
• The pattern of inheritance of such Mendelian disorders can be traced in a family by the pedigree analysis.  

Mendelian disorders may be dominant or recessive.  

• Most common and prevalent Mendelian disorders are hemophilia, cystic fibrosis, sickle-cell anemia, color blindness, phenylketonuria, thalassemia, etc.  

Hemophilia 

In this disease, a single protein is a part of the cascade of proteins involved in the clotting of blood is affected. Due to this, in an affected individual, a simple cut will result in non-stop bleeding. 

• Sex-linked recessive disease. 
• The disease is transmitted from unaffected female carrier to some of the male progeny. 
• Female becoming hemophilic is extremely rare because the mother of such a female should be a carrier, and the father should be hemophilic. 
• The affected person transmits the disease only to the son, not to the daughter. 
• Daughter can receive the disease from both mother and father. 

Sickle-Cell Anemia 

This is an autosome linked recessive trait.  

This disease is transmitted from parents to the offspring when both partners are carriers for the gene.  

• The defect is caused due to substitution of glutamic acid (Glu) by valine (Val) at the sixth position of the beta-globin chain of the hemoglobin molecule. 
• Substitution of amino acid takes place due to the single base substitution at the sixth codon of the beta globin gene from GAG to GUG. 
• The mutant hemoglobin molecule undergoes polymerization under low oxygen tension causing the change in the shape of the RBC from biconcave disc to an elongated sickle-like structure. 
• This disease is controlled by a single pair of alleles, HbA and HbS. 
• There are three possible genotypes (HbA HbA, HbA HbS, and HbSHbS. 
• Only homozygous individuals for HbS (HbS HbS) show the diseased phenotype. 
• Heterozygous (HbA HbS) individuals appear apparently unaffected, but they are carrier of the disease as there is a 50 percent probability of transmission of the mutant gene to the progeny. 

Chromosomal Disorders 

• Caused due to absence or excess or abnormal arrangement of one or more chromosomes. 
• Failure of segregation of chromatids during cell division cycle results in the gain or loss of chromosome(s), called aneuploidy. 
• Failure of cytokinesis after the telophase stage of cell division results in an increase in a whole set of chromosomes in an organism, and this phenomenon is called polyploidy. 
• Trisomy: additional copy of a chromosome may be included in an individual (2n + 1).          Monosomy: an individual may lack one of any one pair of chromosomes (2n – 1). 

Down Syndrome 

• Caused due to the presence of an additional copy of chromosome number 21 (trisomy of 21). 
• This disorder was first described by Langdon Down (1866). 
• Short stature with a small round head. With furrowed tongue.  
• Partially opened mouth. 
• Palm is broad with a characteristic palm crease. 
• Physical, psychomotor and mental development is retarded. 

KLINEFELTER’S SYNDROME 

• Caused due to the presence of an additional copy of X-chromosome, resulting in a karyotype of 47, (44+XXY).  
• Overall masculine development. 
• Also develop feminine character (Development of breast, i.e., gynecomastia) 
• Individuals are sterile. 

Summary:

• Sudden inheritable change in DNA sequence and change in genotype and phenotype of an
  organism is called a mutation.
• It is either by loss or gain or change in DNA sequence.
• Pedigree analysis is a representation chart of the family history.
• Genetic disorder is a disease that is caused due to abnormalities in an individual’s DNA.
• Genetic disorders are categorized into two ~ Mendelian disorder and chromosomal
  disorder.
• Mendelian disorder – hemophilia occurs due to deficiency of plasma thromboplastin
  during which the exposed blood does not clot.
• Sickle cell anemia ~ it is a blood disease during which the RBC become sickle shape as
  ‘compared to the normal RBC.
• Chromosomal disorder are of two types -autosomal chromosomal changes and sex
  chromosomal changes.
• Down syndrome – (trisomy of 21) syndrome is characterized by a round face, broad neck,
  folded eyelids, low IQ etc.
• Klinefelter syndrome – this disorder is caused due to the presence of an additional copy
  of X chromosome that is with karyotype of 47 chromosomes; such development may
  resulting feminine development (development of breast, is observed).