title: Screening of Kozak-motif-located SNPs and analysis of their association with human diseases.
abstract: The Kozak motif, which is located near the translational start codon, often regulates the protein translation. Moreover, it is believed that the conserved positions -3 and +4 contribute the most. Since changes that occur in this motif have a great impact on protein yield and in some cases are associated with disease, we screened the human SNP database for all Kozak-motif-located SNPs (kSNPs) and focused on the strong-changed kSNPs (sckSNPs). Many intron-located and synonymous SNPs are reported to be associated with disease, though the mechanisms underlying these associations are poorly understood. Here, we performed haplotype analysis on sckSNP-containing genes and found that there are some sckSNPs that exist in the same haplotype blocks of reported intron-located and synonymous disease-associated SNPs, indicating that those kSNPs could be a true risk factor for disease-association by affecting the efficiency of protein expression. Our findings provide a candidate explanation for how diseases are associated with intron-located and synonymous SNPs.
authors.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) and Shanghai Jiao Tong University School of Medicine (SJTUSM), 225 South Chong Qing Road, Shanghai 200025, PR China.
authors.forename: Heng
authors.initials: H
authors.lastname: Xu
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: You
authors.forename: Yufang
authors.initials: Y
authors.lastname: Zheng
authors.forename: Yujie
authors.initials: Y
authors.lastname: Fu
authors.forename: Quan
authors.initials: Q
authors.lastname: Tang
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Zejun
authors.initials: Z
authors.lastname: Wei
authors.forename: Bin
authors.initials: B
authors.lastname: Lin
authors.forename: Yang
authors.initials: Y
authors.lastname: Shu
authors.forename: Yufei
authors.initials: Y
authors.lastname: Zhu
authors.forename: Landian
authors.initials: L
authors.lastname: Hu
authors.forename: Xiangyin
authors.initials: X
authors.lastname: Kong
mesh_terms: D018387:Codon, Initiator / Q000235:genetics*; D004252:DNA Mutational Analysis; D004194:Disease / Q000235:genetics*; D005091:Exons / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007438:Introns / Q000235:genetics*; D010442:Peptide Chain Initiation, Translational / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D018387:Codon, Initiator