The landscape of human STR variation

Area of Science:

• Human Genetics
• Genomics
• Population Genetics

Background:

• Short tandem repeats (STRs) are highly polymorphic regions in the human genome.
• STRs are implicated in genetic diseases and widely used in forensics, population genetics, and genetic genealogy.
• Comprehensive data on human STR variation remains limited.

Purpose of the Study:

• To conduct the largest-scale analysis of human STR variation to date.
• To analyze determinants of STR variation and assess the human reference genome's representation of STR alleles.
• To identify STR loci with common loss-of-function alleles and estimate linkage disequilibrium with SNPs.

Main Methods:

• Analysis of nearly 700,000 STR loci from over 1000 individuals in Phase 1 of the 1000 Genomes Project.
• Application of extensive quality control measures to ensure reliable allelic spectra.
• Utilizing the generated STR call set for various analytical investigations.

Main Results:

• Reliable allelic spectra were obtained for approximately 90% of analyzed STR loci.
• Determinants of STR variation were analyzed, alongside an assessment of STR allele representation in the human reference genome.
• STR loci with common loss-of-function alleles were identified, and linkage disequilibrium with common SNPs was estimated.

Conclusions:

• This study provides unprecedented insights into human STR variation.
• The findings significantly advance our understanding of genetic diversity beyond classical point mutations.
• The comprehensive STR data has broad implications for genetic research, disease studies, and forensic applications.