The 1000 Genomes Project Consortium has characterized the geographic and functional spectrum of human genetic variation by sequencing 1,092 individuals from 14 populations, using a combination of low-coverage whole-genome and exome sequencing. They developed methods to integrate information from multiple algorithms and data sources, resulting in a validated haplotype map of 38 million single nucleotide polymorphisms (SNPs), 1.4 million short insertions and deletions, and over 14,000 large deletions. The study reveals that individuals from different populations carry distinct profiles of rare and common variants, with low-frequency variants showing substantial geographic differentiation. Evolutionary conservation and coding consequences are key determinants of purifying selection strength, and rare-variant load varies across biological pathways. The resource captures up to 98% of accessible single nucleotide polymorphisms at a frequency of 1% in related populations, enabling the analysis of common and low-frequency variants in diverse populations. The project's data are widely used in medical genetics, including screening variants in exome data from individuals with genetic disorders and cancer genome projects, and for imputing genotypes in existing genome-wide association studies (GWAS). The analysis of low-frequency variation highlights the pervasive effects of purifying selection and how it interacts with population history to lead to substantial local differentiation.The 1000 Genomes Project Consortium has characterized the geographic and functional spectrum of human genetic variation by sequencing 1,092 individuals from 14 populations, using a combination of low-coverage whole-genome and exome sequencing. They developed methods to integrate information from multiple algorithms and data sources, resulting in a validated haplotype map of 38 million single nucleotide polymorphisms (SNPs), 1.4 million short insertions and deletions, and over 14,000 large deletions. The study reveals that individuals from different populations carry distinct profiles of rare and common variants, with low-frequency variants showing substantial geographic differentiation. Evolutionary conservation and coding consequences are key determinants of purifying selection strength, and rare-variant load varies across biological pathways. The resource captures up to 98% of accessible single nucleotide polymorphisms at a frequency of 1% in related populations, enabling the analysis of common and low-frequency variants in diverse populations. The project's data are widely used in medical genetics, including screening variants in exome data from individuals with genetic disorders and cancer genome projects, and for imputing genotypes in existing genome-wide association studies (GWAS). The analysis of low-frequency variation highlights the pervasive effects of purifying selection and how it interacts with population history to lead to substantial local differentiation.