Genetic variation in an individual human exome.

Area of Science:

• Genomics
• Bioinformatics
• Human Genetics

Background:

• Characterizing human genetic variation is crucial for understanding individual phenotypes and enabling personalized genomics.
• The exome, containing exons, is a key focus for identifying functional genetic variations.
• Previous studies have laid the groundwork for exome sequencing and variant analysis.

Purpose of the Study:

• To analyze approximately 12,500 coding variants in an individual's exome.
• To identify and characterize variants with potential major effects on protein function.
• To refine the set of variants relevant for personalized genomics and potential improvements to the human reference genome.

Main Methods:

• Exome sequencing to identify genetic variants.
• Bioinformatic analysis to filter and prioritize variants.
• Prediction of protein function impact for identified variants.

Main Results:

• Identified approximately 10,400 nonsynonymous single nucleotide polymorphisms (nsSNPs), with 15-20% being rare.
• Predicted approximately 1,500 nsSNPs to affect protein function, often being heterozygous, rare, or novel.
• Characterized ~700 coding indels, with about half not causing frameshifts due to amino acid triplet lengths or gene termini.

Conclusions:

• Reduced the set of nonsilent coding variants by an 8-fold factor to those most likely to impact protein function.
• The majority of coding variants are common and functionally neutral.
• The study provides a framework for analyzing exome variation and highlights potential for improving the human reference genome.