Dataset Information

Linkage disequilibrium and signatures of positive selection around LINE-1 retrotransposons in the human genome.

ABSTRACT: 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.

SUBMITTER: Kuhn A

PROVIDER: S-EPMC4050588 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Linkage disequilibrium and signatures of positive selection around LINE-1 retrotransposons in the human genome.

Kuhn Alexandre A Ong Yao Min YM Cheng Ching-Yu CY Wong Tien Yin TY Quake Stephen R SR Burkholder William F WF

Proceedings of the National Academy of Sciences of the United States of America 20140520 22

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 surro ...[more]

PMID: 24847061

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Project description:The Lundehund is an old dog breed with remarkable anatomical features including polydactyly in all four limbs and extraordinary flexibility of the spine. We genotyped 28 Lundehund using the canine Illumina high density beadchip to estimate the effective population size (Ne) and inbreeding coefficients as well as to identify potential regions of positive selection. The decay of linkage disequilibrium was slow with r2=0.95 in 50 kb distance. The last 7-200 generations ago, Ne was at 10-13. An increase of Ne was noted in the very recent generations with a peak value of 19 for Ne at generation 4. The FROH estimated for 50-, 65- and 358-SNP windows were 0.87, 087 and 0.81, respectively. The most likely estimates for FROH after removing identical-by-state segments due to linkage disequilibria were at 0.80-0.81. The extreme loss of heterozygosity has been accumulated through continued inbreeding over 200 generations within a probably closed population with a small effective population size. The mean inbreeding coefficient based on pedigree data for the last 11 generations (FPed=0.10) was strongly biased downwards due to the unknown coancestry of the founders in this pedigree data. The long-range haplotype test identified regions with genes involved in processes of immunity, olfaction, woundhealing and neuronal development as potential targets of selection. The genes QSOX2, BMPR1B and PRRX2 as well as MYOM1 are candidates for selection on the Lundehund characteristics small body size, increased number of digits per paw and extraordinary mobility, respectively. The objectives of the present study were to genotype 28 Lundehund using the canine Illumina high density beadchip (Illumina, San Diego, CA, USA) to estimate the effective population size (Ne) from data on linkage disequilibria (LD). We identified runs of homozygosity (ROH) as regions with a local loss of genetic variation. Inbreeding coefficients were calculated on the basis of pedigree data (FPed) and genotype information (FROH, FIS) to compare the results of these different methods for this population. We applied the long-range haplotype test to search for potential selective sweeps.

Dataset Information

Linkage disequilibrium and signatures of positive selection around LINE-1 retrotransposons in the human genome.

Publications

Linkage disequilibrium and signatures of positive selection around LINE-1 retrotransposons in the human genome.

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