Following the LINEs: An Analysis of Primate Genomic Variation at Human-Specific LINE-1 Insertion Sites

The hominid SINE-VNTR-Alu (SVA) retrotransposons represent a repertoire of genomic variation which could have significant effects on genome function. A human-specific SVA in the promoter region of the gene leucine-rich repeats and immunoglobulin-like domains 2 (LRIG2), which we termed SVA_LRIG2, is a common retrotransposon insertion polymorphism (RIP), defined as an element which is polymorphic for its presence or absence in the genome. We hypothesised that this RIP might be associated with differential levels of expression of LRIG2. The RIP genotype of SVA_LRIG2 was determined in a subset of frontal cortex DNA samples from the North American Brain Expression Consortium (NABEC) cohort and was imputed for a larger set of that cohort. Utilising available frontal cortex total RNA-seq and CpG methylation data for this cohort, we observed that increased allele dosage of SVA_LRIG2 was non-significantly associated with a decrease in transcription from the region and significantly associated with increased methylation of the CpG probe nearest to SVA_LRIG2, i.e., SVA_LRIG2 is a significant methylation quantitative trait loci (mQTL) at the LRIG2 locus. These data are consistent with SVA_LRIG2 being a transcriptional regulator, which in part may involve epigenetic modulation.

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Somatic LINE-1 retrotransposition in cortical neurons and non-brain tissues of Rett patients and healthy individuals

10.1101/506758 ◽

2018 ◽

Author(s):

Boxun Zhao ◽

Qixi Wu ◽

Adam Yongxin Ye ◽

Jing Guo ◽

Xianing Zheng ◽

...

Keyword(s):

Cortical Neurons ◽

Genomic Diversity ◽

Healthy Controls ◽

Genome Wide ◽

Retrotransposon Family ◽

Somatic Tissues ◽

The Brain ◽

Specific Line ◽

Human Specific ◽

Brain Tissues

AbstractMounting evidence supports that LINE-1 (L1) retrotransposition can occur postzygotically in healthy and diseased human tissues, contributing to genomic mosaicism in the brain and other somatic tissues of an individual. However, the genomic distribution of somatic L1Hs (Human-specific LINE-1) insertions and their potential impact on carrier cells remain unclear. Here, using a PCR-based targeted bulk sequencing approach, we profiled 9,181 somatic insertions from 20 postmortem tissues from five Rett patients and their matched healthy controls. We identified and validated somatic L1Hs insertions in both cortical neurons and non-brain tissues. In Rett patients, somatic insertions were significantly depleted in exons—mainly contributed by long genes—than healthy controls, implying that cells carrying MECP2 mutations might be defenseless against a second exonic L1Hs insertion. We observed a significant increase of somatic L1Hs insertions in the brain compared with non-brain tissues from the same individual. Compared to germline insertions, somatic insertions were less sense-depleted to transcripts, indicating that they underwent weaker selective pressure on the orientation of insertion. Our observations demonstrate that somatic L1Hs insertions contribute to genomic diversity and MECP2 dysfunction alters their genomic patterns in Rett patients.Author SummaryHuman-specific LINE-1 (L1Hs) is the most active autonomous retrotransposon family in the human genome. Mounting evidence supports that L1Hs retrotransposition occurs postzygotically in the human brain cells, contributing to neuronal genomic diversity, but the extent of L1Hs-driven mosaicism in the brain is debated. In this study, we profiled genome-wide L1Hs insertions among 20 postmortem tissues from Rett patients and matched controls. We identified and validated somatic L1Hs insertions in both cortical neurons and non-brain tissues, with a higher jumping activity in the brain. We further found that MECP2 dysfunction might alter the genomic pattern of somatic L1Hs in Rett patients.

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Identification and characterization of occult human-specific LINE-1 insertions using long-read sequencing technology

Nucleic Acids Research ◽

10.1093/nar/gkz1173 ◽

2019 ◽

Vol 48 (3) ◽

pp. 1146-1163 ◽

Cited By ~ 15

Author(s):

Weichen Zhou ◽

Sarah B Emery ◽

Diane A Flasch ◽

Yifan Wang ◽

Kenneth Y Kwan ◽

...

Keyword(s):

Genetic Disorders ◽

Sequencing Data ◽

Detection Rates ◽

Short Read ◽

Long Read ◽

Genomic Regions ◽

Human Genetic Disorders ◽

Specific Line ◽

Human Specific

Abstract Long Interspersed Element-1 (LINE-1) retrotransposition contributes to inter- and intra-individual genetic variation and occasionally can lead to human genetic disorders. Various strategies have been developed to identify human-specific LINE-1 (L1Hs) insertions from short-read whole genome sequencing (WGS) data; however, they have limitations in detecting insertions in complex repetitive genomic regions. Here, we developed a computational tool (PALMER) and used it to identify 203 non-reference L1Hs insertions in the NA12878 benchmark genome. Using PacBio long-read sequencing data, we identified L1Hs insertions that were absent in previous short-read studies (90/203). Approximately 81% (73/90) of the L1Hs insertions reside within endogenous LINE-1 sequences in the reference assembly and the analysis of unique breakpoint junction sequences revealed 63% (57/90) of these L1Hs insertions could be genotyped in 1000 Genomes Project sequences. Moreover, we observed that amplification biases encountered in single-cell WGS experiments led to a wide variation in L1Hs insertion detection rates between four individual NA12878 cells; under-amplification limited detection to 32% (65/203) of insertions, whereas over-amplification increased false positive calls. In sum, these data indicate that L1Hs insertions are often missed using standard short-read sequencing approaches and long-read sequencing approaches can significantly improve the detection of L1Hs insertions present in individual genomes.

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Characterizing nucleotide variation and expansion dynamics in human-specific variable number tandem repeats

10.1101/2021.03.25.437092 ◽

2021 ◽

Author(s):

Meredith M. Course ◽

Arvis Sulovari ◽

Kathryn Gudsnuk ◽

Evan E. Eichler ◽

Paul N. Valdmanis

Keyword(s):

Human Genome ◽

Tandem Repeats ◽

Repeat Unit ◽

Variable Number ◽

Genomic Variation ◽

Repeat Motif ◽

1000 Genomes Project ◽

1000 Genomes ◽

Variable Number Tandem Repeats ◽

Human Specific

AbstractThere are over 55,000 variable number tandem repeats (VNTRs) in the human genome, notable for both their striking polymorphism and mutability. Despite their role in human evolution and genomic variation, they have yet to be studied collectively and in detail, partially due to their large size, variability, and predominant location in non-coding regions. Here, we examine 467 VNTRs that are human-specific expansions, unique to one location in the genome, and not associated with retrotransposons. We leverage publicly available long-read genomes – including from the Human Genome Structural Variant Consortium – to ascertain the exact nucleotide composition of these VNTRs, and compare their composition of alleles. We then confirm repeat unit composition in over 3000 short-read samples from the 1000 Genomes Project. Our analysis reveals that these VNTRs contain remarkably structured repeat motif organization, modified by frequent deletion and duplication events. While overall VNTR compositions tend to remain similar between 1000 Genomes Project super-populations, we describe a notable exception with substantial differences in repeat composition (in PCBP3), as well as several VNTRs that are significantly different in length between super-populations (in ART1, PROP1, WDR60, and LOC102723906). We also observe that most of these VNTRs are expanded in archaic human genomes, yet remain stable in length between single generations. Collectively, our findings indicate that repeat motif variability, repeat composition, and repeat length are all informative modalities to consider when characterizing VNTRs and their contribution to genomic variation.

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Review for "Modeling Human‐specific Interlaminar Astrocytes in the Mouse Cerebral Cortex"

10.1002/cne.24979/v2/review1 ◽

2020 ◽

Author(s):

Alexei Verkhratsky

Keyword(s):

Cerebral Cortex ◽

Mouse Cerebral Cortex ◽

Human Specific

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EVALUATION OF PTYCHOBOTHRIDEAN CESTODES USING RANDOM AMPLIFIED POLYMORPHIC DNA (RAPD) MARKERS FROM FRESH WATER FISHES IN GODAVARI BASIN (M.S.) INDIA

FLORA AND FAUNA ◽

10.33451/florafauna.v23i2pp461-467 ◽

2017 ◽

Vol 23 (2) ◽

Cited By ~ 1

Author(s):

SUNITA BORDE ◽

ASAWARI FARTADE ◽

AMOL THOSAR ◽

RAHUL KHAWAL

Keyword(s):

Fresh Water ◽

Rapd Markers ◽

Random Amplified Polymorphic Dna ◽

Band Pattern ◽

Genomic Variation ◽

Polymorphic Band ◽

Rapd Profile ◽

Band Size ◽

Pcr Product ◽

The Common

Ptychobothridean genera like Senga and Circumoncobothrium are the common parasites of fresh water fishes. The genotypic study of these parasites was taken by RAPD. The RAPD profile of these two parasites were not similar to each other as depicted by the band pattern in picture. These results suggest the presence of inter-specific polymorphism among cestode parasites of two different genera for RAPD analysis. The present study demonstrated that genetic differentiation of cestode parasites could be accomplished on the basis of genomic variation with polymorphic band pattern using RAPD. All the detected bands (PCR product) were polymorphic and band size ranged from 500-5000 bp in length. The RAPD of profiles using GBO-31, GBO-32, GBO-33, GBO-34, GBO-35 and GBO-36. Primers were able to characterize inter-specific polymorphism among the two genus ( Senga and Circumoncobothrium ). Genetic analysis suggests that Senga and Circumoncobothrium show genetic diversity with respect to RAPD patterns using all the six primers used for the present study. The genetic distance between the analyzed genuses ranged from 0.14 to 0.80. The differentiation of the two parasites on the basis of genetic markers could greatly facilitate study on the biology of these parasites.

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