Southern blotting is used to analyze DNA. A clinical application is confirming Huntington's disease (HD). In HD, a patient's Southern blot shows an expanded band. This expansion represents:

• A A deletion of exon 1 of the HTT gene
• B A CpG island methylation causing gene silencing
• C A translocation between chromosomes 4 and 7
• D An expanded CAG trinucleotide repeat (>35 repeats) in exon 1 of HTT encoding a polyglutamine tract ✓

Explanation

Huntington's disease is caused by an expanded CAG trinucleotide repeat (normally 10–35 repeats; >35 = disease, >40 = full penetrance) in exon 1 of the HTT gene on chromosome 4p16.3. The expanded repeat encodes a polyglutamine (polyQ) tract in huntingtin protein that forms toxic nuclear aggregates. On Southern blot, the restriction fragment containing the repeat region appears larger (shifted) in affected alleles. The length of expansion correlates inversely with age of onset (anticipation). PCR-based sizing of CAG repeats is now the primary diagnostic method.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.