Mutations and Genetic Disorders: Quick Revision

A brief note on Mutations and Genetic Disorders. Read it before a test. Try each question at the end before you open its answer.

Mutations

• Mutation: a sudden heritable change in DNA. Mutagens include ultraviolet light, X rays and chemicals.
• Point mutation: one base pair changes. It is silent (same amino acid), missense (another amino acid) or nonsense (a stop codon).
• Frameshift: one or two bases inserted or deleted. Every later codon changes. Three bases keep the frame.
• Chromosomal aberrations: deletion, duplication, inversion and translocation. Aneuploidy is the gain or loss of single chromosomes. Polyploidy is a gain of whole sets.

Mendelian disorders

• Thalassaemia: autosomal recessive. Too little alpha or beta globin. Alpha: genes on chromosome 16. Beta: one gene on chromosome 11.
• Haemophilia and colour blindness: X-linked recessive.
• Sickle-cell anaemia, phenylketonuria and cystic fibrosis: autosomal recessive (in NCERT, not named in the NTA text).
• Two carriers (Aa × Aa): $\tfrac{1}{4}$ affected, $\tfrac{1}{2}$ carriers, $\tfrac{1}{4}$ normal. An unaffected child is a carrier with a chance of $\tfrac{2}{3}$.

Chromosomal disorders

• Non-disjunction: gives $n + 1$ and $n - 1$ gametes. Meiosis I: all four abnormal. Meiosis II: two abnormal, two normal.
• Down syndrome: trisomy 21, 47 chromosomes. Klinefelter: 47, XXY, male, sterile. Turner: 45, X, female, sterile.
• Chi-square: $\sum (O - E)^2 / E$. For 1 degree of freedom, the critical value at the 5 per cent level is 3.84.

A worked example

Two carriers of thalassaemia have 4 children. What is the chance that none is affected?

1. Each child is unaffected with a chance of $\tfrac{3}{4}$.
2. For four children: $\left(\tfrac{3}{4}\right)^4 = \tfrac{81}{256}$, which is about 31.6 per cent.

Practice with new numbers

A program to try

The program gives the chromosome numbers of the syndromes and a chi-square value.

Mistakes to avoid

• Mixing up Turner and Klinefelter. Turner is 45, X. Klinefelter is 47, XXY.
• Calling a carrier a patient. A carrier has one copy and is healthy.
• Saying that every deletion shifts the frame. A deletion of three bases keeps it.
• Giving $\tfrac{1}{3}$ for a healthy child to be a carrier. The chance is $\tfrac{2}{3}$.

Check yourself

1. How many chromosomes does a person with Down syndrome have?

2. What kind of mutation changes GAG to GAA, both for glutamic acid?

3. What is the chance that a child of two carriers is a carrier?

4. At which stage of meiosis does a failure give two normal and two abnormal gametes?

Sources

• NCERT (2023). Biology, Textbook for Class XII, chapter 4.
• Clark M. A., Douglas M. and Choi J. (2018). Biology 2e, OpenStax, chapter 13.2.