This study provides a comprehensive analysis of CpG islands in human chromosomes 21 and 22. CpG islands are regions of DNA with high G+C content and a high observed CpG/expected CpG ratio, and they are important for gene regulation. The original definition of CpG islands, proposed by Gardiner-Garden and Frommer, was based on a 200-bp stretch of DNA with a G+C content of at least 50% and an observed CpG/expected CpG ratio of at least 0.6. However, this definition included many sequences not associated with gene control regions, such as Alu repetitive elements. The authors used complete genomic sequences of human chromosomes 21 and 22 to examine the properties of CpG islands in different sequence classes. They developed a search algorithm to identify CpG islands and modified the original criteria to exclude Alu elements and many CpG islands not located in gene promoters. The new criteria included a G+C content of at least 55% and an observed CpG/expected CpG ratio of at least 0.65, which resulted in a significant reduction in the number of CpG islands identified. The study also compared CpG suppression in the human genome with that in other organisms, including Drosophila melanogaster and Saccharomyces cerevisiae. The human genome showed strong CpG suppression, while Drosophila showed slight suppression. This finding is compatible with recent detection of 5-methylcytosine in Drosophila and suggests that S. cerevisiae may have, or once had, CpG methylation. The study found that CpG islands are more likely to be associated with the 5' regions of genes and that they are less common in exonic regions. The modified criteria helped to exclude Alu sequences previously identified as part of 5' CpG islands. The results suggest that the new criteria provide a more accurate definition of CpG islands and may be useful for studying the role of methylation in promoter silencing. The study also highlights the importance of CpG islands in gene regulation and their potential role in diseases such as cancer.This study provides a comprehensive analysis of CpG islands in human chromosomes 21 and 22. CpG islands are regions of DNA with high G+C content and a high observed CpG/expected CpG ratio, and they are important for gene regulation. The original definition of CpG islands, proposed by Gardiner-Garden and Frommer, was based on a 200-bp stretch of DNA with a G+C content of at least 50% and an observed CpG/expected CpG ratio of at least 0.6. However, this definition included many sequences not associated with gene control regions, such as Alu repetitive elements. The authors used complete genomic sequences of human chromosomes 21 and 22 to examine the properties of CpG islands in different sequence classes. They developed a search algorithm to identify CpG islands and modified the original criteria to exclude Alu elements and many CpG islands not located in gene promoters. The new criteria included a G+C content of at least 55% and an observed CpG/expected CpG ratio of at least 0.65, which resulted in a significant reduction in the number of CpG islands identified. The study also compared CpG suppression in the human genome with that in other organisms, including Drosophila melanogaster and Saccharomyces cerevisiae. The human genome showed strong CpG suppression, while Drosophila showed slight suppression. This finding is compatible with recent detection of 5-methylcytosine in Drosophila and suggests that S. cerevisiae may have, or once had, CpG methylation. The study found that CpG islands are more likely to be associated with the 5' regions of genes and that they are less common in exonic regions. The modified criteria helped to exclude Alu sequences previously identified as part of 5' CpG islands. The results suggest that the new criteria provide a more accurate definition of CpG islands and may be useful for studying the role of methylation in promoter silencing. The study also highlights the importance of CpG islands in gene regulation and their potential role in diseases such as cancer.