GENETIC DISORDERS

 GENETIC DISORDERS

Genetic disorders are the disorders due to change in genes or chromosomes.

Genetic Disorders

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1. Mendelian Disorders                                                            2. Chromosomal Disorders

                    ↓                                                                                                        ↓

            Haemophilia                                                                                 Down's Syndrome

          Sickle cell anaemia                                                                        Turner's Syndrome

          Colour blindness                                                                            Klinefelter's Syndrome

          Phenyl-ketonuria

           Thalassemia

          Cystic fibrosis

1. Mendelian Disorders :-

• The disorders caused by  alteration or mutation in the single gene.
• E.g  Haemophilia, Sickle cell anaemia, Colour blindness, Phenyl-ketonuria, Thalassemia, Cystic fibrosis, etc.
• The pattern of inheritance of Mendelian disorders can be traced in a family by pedigree analysis.
• Mendelian disorders may be dominant or recessive.
• Pedigree analysis helps to understand whether the trait is dominant or recessive.

I )  HAEMOPHILIA ( ROYAL DISEASE ) =

• Sex linked ( X-linked ) recessive disease.
• In this, a protein involved in the blood clotting is affected.
• A simple cut results in non-stop bleeding.
• It is controlled by a pair of allele, H & h. 
• H is normal allele and h is responsible for haemophilia.
• In females, haemophilia is very rare because it happens only when mother is at least carrier and father haemophilic ( unviable in the later stage of life ).

II )  COLOUR BLINDNESS =

• It is a sex-linked ( X-linked ) recessive disorder due to defect in either red or green cone cells of eye. It results in failure to discriminate between red and green colour.
• It is due to mutation in some genes in X chromosome.
• It occurs in 8% of males and only 0.4% of females. This is due to the genes are X-linked.
• Normal allele is dominant (C). Recessive allele (c) cause colour blindness.
• The son of a heterozygous women (carrier) has a 50 % chance of being colour bind.
• A daughter will be colour blind only when her mother is at least a carrier and her father is colour blind.

III )  Sickle cell anaemia =

• This is an autosome linked recessive trait.
• It can be transmitted from parents to the offspring when both the partners are carrier (heterozygous) for the gene.
• The disease is controlled by a pair of allele, HbA & HbS.
• Homozygous dominant (HbA HbA) : Normal
• Heterozygous (HbA HbS) : Carrier ; sickle cell trait
• Homozygous recessive (HbS HbS) : Affected
• This defect is caused by the substitution of Glutamic acid (Glu) by Valine (Val) at the 6th position of the β-globin chain of haemoglobin.
• This is due to single base substitution at the 6th codon of β-globin gene from GAG to GUG.
• The mutant haemoglobin molecule undergoes polymerization under low oxygen tension causing the change in shape of the RBC from biconcave disc to elongated sickle like structure.

Sickle cell anaemia is a qualitative problem (synthesis of an incorrectly functioning globin).

IV )  Phenylkeatonuria (PKU) =

• An inborn error of metabolism.
• Autosomal recessive trait.
• It is due to mutation in the gene that codes for the enzyme phenyl alanine hydroxylase. This enzyme converts an amino acid phenylalanine into tyrosine.
• The affected individual lacks this enzyme. As a result, phenylalanine accumulates and converts into phenyl pyruvic acid and other derivatives.

• Phenyl pyruvic acid ad other derivatives accumulate in brain resulting in mental retardation. These are also excreted through urine because of poor absorption by kidney.

V )  Thalassemia = 

• It is an autosome-linked recessive blood disease.
• It is transmitted from unaffected carrier (heterozygous) parents to the offspring.
• It is due to mutation or deletion.
• It results in reduced synthesis of one of the 𝛂 and 𝛃 globin chains of haemoglobin. It froms abnormal haemoglobin and causes anaemia.
• Thalassemia is a quantitative problem (synthesis of few globin molecules).

Based on the chain affected, thalassemia is two types : 𝜶 thalassemia and 𝞫 thalassemia.

𝞪 Thalassemia

• Here, production of 𝞪 globin chain is affected.
• It is controlled by two closely linked genes HBA1 and HBA2 on chromosome 16 of each parent.
• Mutation or deletion of one or more of the four genes causes the disease.
• The more genes affected, the less 𝞪 globin molecules produced.

𝞫 Thalassemia

• Here, production of 𝞫 globin chain is affected.
• It is controlled by a single gene HBB on chromosome 11 of each parent.
• Mutation of one or both the genes causes the disease.

2. Chromosomal Disorders :-

The disorders caused due to absence or excess or abnormal arrangement of the one or more chromosomes.

I )  Down's Syndrome (Mongolism) =

• It is the presence of an additional copy of chromosome number 21 (trisomy of 21).
• Genetic constitution : 45 A + XX or 45 A + XY (i.e 47 chromosomes).

Features

• Short statured with small round head.
• Broad flat face.
• Furrowed big tongue & partially open mouth.
• Broad palm with characteristic palm simian crease.
• Many "loops" on finger tips.
• Retarded physical, psychomotor and mental development.
• Congenital heart disease.

II )  Turner's Syndrome =

• This is the absence of one the X chromosome in female.
• Genetic constitution : 44A + X0 (i.e 45 chromosomes).

Features

• Sterile, Ovaries are rudimentary.
• Lack of other secondary sexual characters.
• Dwarf.
• Mentally retarded.

III )  Klinedelter's Syndrome =

• It is the presence of an additional copy of X-chromosome in male.
• Genetic constitution : 44A + XXY (i.e 47 chromosomes).

Features

• Overall masculine development, however, feminine development (development of breast, i.e., Gynaecomastia) ia also expressed.
• Sterile.
• Metally retarded.