Mendelian Disorders
Read the following passage carefully and answer the given questions.
Genetic disorders may be grouped into two categories – Mendelian disorders and Chromosomal disorders. Mendelian disorders are mainly determined by alteration or mutation in a single gene. These disorders are transmitted to the offspring on the same lines as in the principle of inheritance. The pattern of inheritance of such Mendelian disorders can be traced in a family by pedigree analysis. Most common and prevalent Mendelian disorders are Haemophilia, Cystic fibrosis, Sickle-cell anaemia, Colour blindness, Phenylketonuria, Thalassemia, etc. The 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 or an autosome.
Which one of the following substitutions is a cause of sickle-cell anaemia?
Answer & explanation
Correct answer: option 3
The correct answer is Option (3) → Substitution of glutamic acid by valine at the sixth position of the beta globin chain.
Sickle-cell anaemia is an autosome-linked recessive trait. It is caused by a single base change in the sixth codon of the beta globin gene, from GAG to GUG. This changes the amino acid glutamic acid (Glu) into valine (Val) at the sixth position of the beta globin chain. Under low oxygen the changed haemoglobin molecules join into long chains. They bend the red blood cell from a biconcave disc into a sickle shape.
(1) Substitution of valine by aspartic acid at the sixth position of the beta globin chain. — Incorrect. The change is in the other direction. Valine is the new amino acid, and glutamic acid is the one it replaces.
(2) Substitution of glutamic acid by alanine at the sixth position of the beta globin chain. — Incorrect. The amino acid that is lost is right, but the one that replaces it is wrong. It is valine, not alanine.
(3) Substitution of glutamic acid by valine at the sixth position of the beta globin chain. — Correct. This is the change caused by GAG becoming GUG.
(4) Substitution of glycine by methionine at the sixth position of the beta globin chain. — Incorrect. Glycine and methionine are not involved in this disease.
Note: The passage is taken from NCERT. NTA has put lines of the NCERT text together to make it. 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).”
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