A map of human genome variation from population-scale sequencing

Area of Science:

• Genomics
• Human Genetics
• Bioinformatics

Background:

• The 1000 Genomes Project aims to deeply characterize human genome sequence variation.
• Understanding genotype-phenotype relationships requires a comprehensive genetic variation dataset.

Purpose of the Study:

• To develop and compare genome-wide sequencing strategies using high-throughput platforms.
• To create a foundational dataset of human genetic variation for future research.

Main Methods:

• Low-coverage whole-genome sequencing of 179 individuals across four populations.
• High-coverage sequencing of two parent-offspring trios.
• Exon-targeted sequencing of 697 individuals from seven populations.

Main Results:

• Catalogued ~15 million single nucleotide polymorphisms, 1 million short insertions/deletions, and 20,000 structural variants, with most previously undescribed.
• Captured >95% of common human genetic variation accessible in individuals.
• Estimated de novo germline mutation rate at ~10^-8 per base pair per generation.

Conclusions:

• The pilot phase successfully catalogued common human genetic variation, providing a valuable resource for association and functional studies.
• The data reveals insights into natural selection, showing reduced variation near genes due to linked selection.
• The developed methods and public data will facilitate subsequent phases of human genetic research.