title: Polymorphic L1 retrotransposons are frequently in strong linkage disequilibrium with neighboring SNPs.
abstract: L1 retrotransposons have been the major driver of structural variation of the human genome. L1 insertion polymorphism (LIP)-mediated genomic variation can alter the transcriptome and contribute to the divergence of human phenotypes. To assess this possibility, a genome-wide association study (GWAS) including LIPs is required. Toward this ultimate goal, the present study examined linkage disequilibrium between six LIPs and their neighboring single nucleotide polymorphisms (SNPs). Genomic PCR and sequencing of L1-plus and -minus alleles from different donors revealed that all six LIPs were in strong linkage disequilibrium with at least one SNP. In addition, comparison of syntenic regions containing the identified SNP nucleotides was performed among modern humans (L1-plus and -minus alleles), archaic humans and non-human primates, revealing two different evolutionary schemes that might have resulted in the observed strong SNP-LIP linkage disequilibria. This study provides an experimental framework and guidance for a future SNP-LIP integrative GWAS.
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors.forename: Saneyuki
authors.initials: S
authors.lastname: Higashino
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ohno
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ishiguro
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan; Center for Biological Resources and Informatics, Tokyo Institute of Technology, Yokohama 226-8501, Japan. Electronic address: yaizawa@bio.titech.ac.jp.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Aizawa
mesh_terms: D000483:Alleles; D000818:Animals; D005075:Biological Evolution; D016678:Genome; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006579:Heterozygote; D015186:Hominidae; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium; D020084:Long Interspersed Nucleotide Elements; D009711:Nucleotides / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D018626:Retroelements; D017422:Sequence Analysis, DNA
chemical_list: D009711:Nucleotides; D018626:Retroelements
keywords: Archaic human; Human genome evolution; Polymorphism; Retrotransposon