Read the following passage carefully and answer the given questions.
Mendelian Disorders
Mendelian disorders are mainly determined by alteration or mutation in the single gene. These disorders are transmitted to the offspring on the same lines as we have studied in the principle of inheritance. The pattern of inheritance of such Mendelian disorders can be traced in a family by the pedigree analysis. Most common and prevalent Mendelian disorders are Haemophilia, Cystic fibrosis, Sickle cell anaemia, Colour blindness, Phenylketonuria, Thalassemia, etc. It is important to mention here that such Mendelian disorders may be dominant or recessive. By pedigree analysis one can easily understand whether the trait in question is dominant or recessive. Similarly, the trait may also be linked to the sex chromosome as in case of haemophilia. It is evident that this X-linked recessive trait shows transmission from carrier female to male progeny.
In Sickle-cell anaemia, the substitution of amino acid results due to the single base substitution in the beta globin gene from GAG to _______ .
Answer & explanation
Correct answer: option 2
The correct answer is Option (2) → GUG
Sickle-cell anaemia is an autosome-linked recessive disease. At the sixth position of the beta globin chain of haemoglobin, the amino acid glutamic acid (Glu) is replaced by valine (Val). This happens because of a single base substitution at the sixth codon of the beta globin gene: GAG becomes GUG. GAG codes for glutamic acid and GUG codes for valine. The changed haemoglobin polymerises when oxygen is low, and the RBCs change from biconcave discs to a sickle shape.
(1) CUG — Incorrect. CUG codes for leucine. It differs from GAG at two places, the first base and the middle base. The mutation in sickle-cell anaemia changes only one base.
(2) GUG — Correct. Only the middle base changes, A to U, and the codon now codes for valine.
(3) AUG — Incorrect. AUG codes for methionine and is the start codon. Two bases differ from GAG.
(4) GUU — Incorrect. GUU also codes for valine, but it differs from GAG at two places. The mutation is a single base substitution.
Figure 4.15 Micrograph of the red blood cells and the amino acid composition of the relevant portion of β-chain of haemoglobin: (a) From a normal individual; (b) From an individual with sickle-cell anaemia
Note: This passage is taken from NCERT as it is. Most CUET (UG) questions come straight from NCERT, so study the book line by line, including figures and their titles.
NCERT Extract:
Mendelian Disorders – “… The defect is caused by the substitution of Glutamic acid (Glu) by Valine (Val) at the sixth position of the beta globin chain of the haemoglobin molecule. The substitution of amino acid in the globin protein results due to the single base substitution at the sixth codon of the beta globin gene from GAG to GUG. The mutant haemoglobin molecule undergoes polymerisation under low oxygen tension causing the change in the shape of the RBC from biconcave disc to elongated sickle like structure (Figure 4.15).”