title: SNPs on human chromosomes 21 and 22 -- analysis in terms of protein features and pseudogenes.
abstract: SNPs are useful for genome-wide mapping and the study of disease genes. Previous studies have focused on SNPs in specific genes or SNPs pooled from a variety of different sources. Here, a systematic approach to the analysis of SNPs in relation to various features on a genome-wide scale, with emphasis on protein features and pseudogenes, is presented. We have performed a comprehensive analysis of 39,408 SNPs on human chromosomes 21 and 22 from the SNP consortium (TSC) database, where SNPs are obtained by random sequencing using consistent and uniform methods. Our study indicates that the occurrence of SNPs is lowest in exons and higher in repeats, introns and pseudogenes. Moreover, in comparing genes and pseudogenes, we find that the SNP density is higher in pseudogenes and the ratio of nonsynonymous to synonymous changes is also much higher. These observations may be explained by the increased rate of SNP accumulation in pseudogenes, which presumably are not under selective pressure. We have also performed secondary structure prediction on all coding regions and found that there is no preferential distribution of SNPs in a -helices, b -sheets or coils. This could imply that protein structures, in general, can tolerate a wide degree of substitutions. Tables relating to our results are available from http://genecensus.org/pseudogene.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, CT 06520-8114, USA.
authors.forename: Suganthi
authors.initials: S
authors.lastname: Balasubramanian
authors.forename: Paul
authors.initials: P
authors.lastname: Harrison
authors.forename: Hedi
authors.initials: H
authors.lastname: Hegyi
authors.forename: Paul
authors.initials: P
authors.lastname: Bertone
authors.forename: Nicholas
authors.initials: N
authors.lastname: Luscombe
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Echols
authors.forename: Patrick
authors.initials: P
authors.lastname: McGarvey
authors.forename: ZhaoLei
authors.initials: Z
authors.lastname: Zhang
authors.forename: Mark
authors.initials: M
authors.lastname: Gerstein
mesh_terms: D000465:Algorithms; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D019992:Databases as Topic; D005091:Exons / Q000235:genetics; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D011544:Pseudogenes / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D011506:Proteins