Following statements were made for fragile X syndrome:

• A. It is caused due to increased numbers of CGG trinucleotide (>200 repeats) in the 5' UTR of FMR1 genes.

• B. Unaffected people do not show any CGG repeats in the 5' UTR of the FMR1 gene.

• C. Expanded numbers of CGG repeats in 5' UTR of FMR1 transcripts causes its premature degradation.

• D. Expansion over 200 repeats leads to methylation of the FMR1 promoter.

• E. Fragile appearance of X chromosome develops due to dissociation of non-histone proteins from the FMR1 locus.

Which one of the following options provides the combination of all correct statements?

Correct option is D

Explanation:

• A . It is caused due to increased numbers of CGG trinucleotide (>200 repeats) in the 5' UTR of FMR1 genes.
  This is correct. Fragile X syndrome is caused by the expansion of CGG trinucleotide repeats in the 5' UTR of the FMR1 gene. More than 200 repeats lead to Fragile X syndrome, while normal individuals have fewer than 45 repeats.

• B. Unaffected people do not show any CGG repeats in the 5' UTR of the FMR1 gene.
  This is incorrect. Unaffected individuals may have small numbers of CGG repeats (e.g., 6-40 repeats). It is the expansion beyond 200 repeats that causes Fragile X syndrome.

• C. Expanded numbers of CGG repeats in 5' UTR of FMR1 transcripts causes its premature degradation.
  This is incorrect. While expanded CGG repeats cause the silencing of the FMR1 gene through methylation of its promoter, they do not cause premature degradation of the transcripts. The gene is effectively "turned off" rather than degraded.

• D. Expansion over 200 repeats leads to methylation of the FMR1 promoter.
  This is correct. When the CGG repeat expands beyond 200 repeats, it leads to methylation of the FMR1 promoter, silencing the gene and preventing expression of the FMR1 protein, which is crucial for cognitive function.

• E. Fragile appearance of X chromosome develops due to dissociation of non-histone proteins from the FMR1 locus.
  This is incorrect. The "fragile" appearance of the X chromosome is not due to dissociation of non-histone proteins. It is a result of structural changes caused by the unmethylated CGG repeats and the absence of the FMR1 protein.

  
  

  Information Booster:

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  1. The CGG repeat expansion in the FMR1 gene causes Fragile X syndrome by leading to gene silencing via promoter methylation.

  2. The FMR1 gene is involved in cognitive development, and its silencing leads to the symptoms of Fragile X syndrome.

  3. Over 200 repeats in the 5' UTR of FMR1 result in methylation and silencing of the gene.

  4. Premature degradation of FMR1 transcripts is not directly linked to CGG repeat expansion, but rather to the silencing of the gene.

  5. The fragile appearance of the X chromosome is not caused by the dissociation of non-histone proteins but by the unmethylated and expanded CGG repeats.