The study introduces a high-throughput and massive paired-end mapping (PEM) method to identify structural variants (SVs) in the human genome. PEM combines the rescue and capture of paired ends of 3-kb fragments, massive 454 sequencing, and computational mapping to identify SVs ~3 kb or larger. The method was applied to map SVs in two individuals, an African and a putatively European, identifying over 1000 SVs. The analysis revealed that the number of SVs among humans is much larger than initially hypothesized, with many potentially affecting gene function. The breakpoint junction sequences of over 200 SVs were determined using a novel pooling strategy and computational analysis, providing insights into the mechanisms of SV formation. The study highlights the importance of incorporating SV detection into human genome sequencing projects to better understand human diversity and genetic diseases.The study introduces a high-throughput and massive paired-end mapping (PEM) method to identify structural variants (SVs) in the human genome. PEM combines the rescue and capture of paired ends of 3-kb fragments, massive 454 sequencing, and computational mapping to identify SVs ~3 kb or larger. The method was applied to map SVs in two individuals, an African and a putatively European, identifying over 1000 SVs. The analysis revealed that the number of SVs among humans is much larger than initially hypothesized, with many potentially affecting gene function. The breakpoint junction sequences of over 200 SVs were determined using a novel pooling strategy and computational analysis, providing insights into the mechanisms of SV formation. The study highlights the importance of incorporating SV detection into human genome sequencing projects to better understand human diversity and genetic diseases.