David J Thomas

Large-scale discovery and genotyping of single-nucleotide polymorphisms in the mouse

Nature Genetics · 2000-04-01 · 421 citations

Genomic regions exhibiting positive selection identified from dense genotype data

Genome Research · 2005-10-26 · 306 citations

The allele frequency spectrum of polymorphisms in DNA sequences can be used to test for signatures of natural selection that depart from the expected frequency spectrum under the neutral theory. We observed a significant (P = 0.001) correlation between the Tajima's D test statistic in full resequencing data and Tajima's D in a dense, genome-wide data set of genotyped polymorphisms for a set of 179 genes. Based on this, we used a sliding window analysis of Tajima's D across the human genome to id…

Conserved noncoding sequences are selectively constrained and not mutation cold spots

Nature Genetics · 2005-12-25 · 237 citations

LS-SNP: large-scale annotation of coding non-synonymous SNPs based on multiple information sources

Computer applications in the biosciences · 2005-04-12 · 227 citations

MOTIVATION: The NCBI dbSNP database lists over 9 million single nucleotide polymorphisms (SNPs) in the human genome, but currently contains limited annotation information. SNPs that result in amino acid residue changes (nsSNPs) are of critical importance in variation between individuals, including disease and drug sensitivity. RESULTS: We have developed LS-SNP, a genomic scale software pipeline to annotate nsSNPs. LS-SNP comprehensively maps nsSNPs onto protein sequences, functional pathways and…

Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome

Genome Research · 2007-06-01 · 220 citations

A key component of the ongoing ENCODE project involves rigorous comparative sequence analyses for the initially targeted 1% of the human genome. Here, we present orthologous sequence generation, alignment, and evolutionary constraint analyses of 23 mammalian species for all ENCODE targets. Alignments were generated using four different methods; comparisons of these methods reveal large-scale consistency but substantial differences in terms of small genomic rearrangements, sensitivity (sequence c…