Linkage disequilibrium and signatures of positive selection around LINE-1 retrotransposons in the human genome.
Insertions of the human-specific subfamily of LINE-1 (L1) retrotransposon are highly polymorphic across individuals and can critically influence the human transcriptome. We hypothesized that L1 insertions could represent genetic variants determining important human phenotypic traits, and performed an integrated analysis of L1 elements and single nucleotide polymorphisms (SNPs) in several human populations. We found that a large fraction of L1s were in high linkage disequilibrium with their surrounding genomic regions and that they were well tagged by SNPs. However, L1 variants were only partially captured by SNPs on standard SNP arrays, so that their potential phenotypic impact would be frequently missed by SNP array-based genome-wide association studies. We next identified potential phenotypic effects of L1s by looking for signatures of natural selection linked to L1 insertions; significant extended haplotype homozygosity was detected around several L1 insertions. This finding suggests that some of these L1 insertions may have been the target of recent positive selection.
Microfluidics Systems Biology Lab, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673;
Alexandre
A
Kuhn
Microfluidics Systems Biology Lab, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673;
Yao Min
YM
Ong
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751;Duke-NUS Graduate Medical School, Singapore 169857;Department of Ophthalmology, National University of Singapore and National University Health Systems, Singapore 119228;
Ching-Yu
CY
Cheng
Singapore Eye Research Institute, Singapore National Eye Centre, Singapore 168751;Duke-NUS Graduate Medical School, Singapore 169857;Department of Ophthalmology, National University of Singapore and National University Health Systems, Singapore 119228;
Tien Yin
TY
Wong
Departments of Bioengineering and Applied Physics and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305; andVisiting Investigator, Institute of Molecular and Cell Biology, A*STAR, Singapore 138673 quake@stanford.edu wfburkholder@gmail.com.
Stephen R
SR
Quake
Microfluidics Systems Biology Lab, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673; quake@stanford.edu wfburkholder@gmail.com.
William F
WF
Burkholder
D019143:Evolution, Molecular; D005786:Gene Expression Regulation / Q000235:genetics; D005828:Genetics, Population / Q000379:methods; D015894:Genome, Human / Q000235:genetics*; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018626:Retroelements / Q000235:genetics*; D012641:Selection, Genetic / Q000235:genetics
D018626:Retroelements
L1-seq; evolution; extended haplotype homozygosity; human genetics; population genetics