Characterization of single-nucleotide polymorphisms in coding regions of human genes

  title={Characterization of single-nucleotide polymorphisms in coding regions of human genes},
  author={Michele Cargill and David Altshuler and James S Ireland and Pamela Sklar and Kristin G. Ardlie and Nila Patil and Charles R. Lane and Esther P. Lim and Nilesh Kalyanaraman and James Nemesh and Liuda Ziaugra and L B Friedland and Alex Rolfe and J. Anthony Warrington and Robert J. Lipshutz and George Q. Daley and Eric S. Lander},
  journal={Nature Genetics},
A major goal in human genetics is to understand the role of common genetic variants in susceptibility to common diseases. This will require characterizing the nature of gene variation in human populations, assembling an extensive catalogue of single-nucleotide polymorphisms (SNPs) in candidate genes and performing association studies for particular diseases. At present, our knowledge of human gene variation remains rudimentary. Here we describe a systematic survey of SNPs in the coding regions… 
Systematic investigation of genetic variability in 111 human genes—implications for studying variable drug response
Genetic variability was decreased in noncoding regions highly conserved between human and rodents, indicating functional relevance of these regions and diversity of coding nonsynonymous SNPs was found lower in regions encoding a known protein sequence motif.
Efficient discovery of single-nucleotide polymorphisms in coding regions of human genes
These data reveal selection against mutations that alter protein structure, and distinct classes of genes under strongly positive vs. negative pressure from natural selection for amino acid replacement (detected by KA/KSratio).
Prediction of nonsynonymous single nucleotide polymorphisms in human disease-associated genes
The level of completeness of the current knowledge of nonsynonymous SNPs in well studied, medically relevant genes is evaluated and the proportion of new variants which can be added with the help of computer-aided mining in EST databases is estimated to be about 50%.
Identification of functional SNPs in the 5-prime flanking sequences of human genes
A method for effective selection of functional, regulatory SNPs that are located in evolutionary conserved 5-prime flanking regions (5'-FR) regions of human genes and influence the activity of the transcriptional regulatory region is proposed.
Large-scale analysis of non-synonymous coding region single nucleotide polymorphisms
It is found that the magnitude of the change in the HMMER E-value caused by an amino acid substitution is a good predictor of whether it is deleterious, and provides internet-accessible display tools for a genomewide collection of SNPs.
Genome-wide analysis of single-nucleotide polymorphisms in human expressed sequences
This comprehensive analysis of human coding region polymorphism provides a public resource for mapping of disease genes and detects tenfold more true HLA-A SNPs than previous analyses of the EST data.
Variation of gene-based SNPs and linkage disequilibrium patterns in the human genome.
The results demonstrate the complexity that must be taken into account when considering SNP variability and LD patterns, while also providing tools necessary for implementation of efficient genome-wide association studies.
Large-scale identification and characterization of genetic variants in asthma candidate genes
Gene-based haplotype analysis of asthma-associated genes in this study revealed that common haplotypes represented 90.5% of chromosomes, and they could be uniquely identified with five or fewer haplotype-tagging SNPs per gene.
Relative effects of mutability and selection on single nucleotide polymorphisms in transcribed regions of the human genome
It is found that the functional category had a significant effect on SNP density and selection affects SNP density in transcribed regions of the genome, suggesting that the probability that a site located in a transcribed region of a gene is polymorphic mostly depends on the mutability of the site.
Identification of 142 single nucleotide polymorphisms in 41 candidate genes for rheumatoid arthritis in the Japanese population
A systematic survey of genomic DNA for SNPs located not only in coding sequences but also in non-coding regions of selected genes of rheumatoid arthritis patients indicated a greater average distance between SNPs than others have reported.