Analysis of lineage-specific Alu subfamilies in the genome of the olive baboon, Papio anubis

© 2018 The Author(s). Background: Alu elements are primate-specific retroposons that mobilize using the enzymatic machinery of L1 s. The recently completed baboon genome project found that the mobilization rate of Alu elements is higher than in the genome of any other primate studied thus far. However, the Alu subfamily structure present in and specific to baboons had not been examined yet. Results: Here we report 129 Alu subfamilies that are propagating in the genome of the olive baboon, with 127 of these subfamilies being new and specific to the baboon lineage. We analyzed 233 Alu insertions in the genome of the olive baboon using locus specific polymerase chain reaction assays, covering 113 of the 129 subfamilies. The allele frequency data from these insertions show that none of the nine groups of subfamilies are nearing fixation in the lineage. Conclusions: Many subfamilies of Alu elements are actively mobilizing throughout the baboon lineage, with most being specific to the baboon lineage

Recently integrated Alu insertions in the squirrel monkey (Saimiri) lineage and application for population analyses

Abstract Background The evolution of Alu elements has been ongoing in primate lineages and Alu insertion polymorphisms are widely used in phylogenetic and population genetics studies. Alu subfamilies in the squirrel monkey (Saimiri), a New World Monkey (NWM), were recently reported. Squirrel monkeys are commonly used in biomedical research and often require species identification. The purpose of this study was two-fold: 1) Perform locus-specific PCR analyses on recently integrated Alu insertions in Saimiri to determine their amplification dynamics, and 2) Identify a subset of Alu insertion polymorphisms with species informative allele frequency distributions between the Saimiri sciureus and Saimiri boliviensis groups. Results PCR analyses were performed on a DNA panel of 32 squirrel monkey individuals for 382 Alu insertion events ≤2% diverged from 46 different Alu subfamily consensus sequences, 25 Saimiri specific and 21 NWM specific Alu subfamilies. Of the 382 loci, 110 were polymorphic for presence / absence among squirrel monkey individuals, 35 elements from 14 different Saimiri specific Alu subfamilies and 75 elements from 19 different NWM specific Alu subfamilies (13 of 46 subfamilies analyzed did not contain polymorphic insertions). Of the 110 Alu insertion polymorphisms, 51 had species informative allele frequency distributions between Saimiri sciureus and Saimiri boliviensis groups. Conclusions This study confirms the evolution of Alu subfamilies in Saimiri and provides evidence for an ongoing and prolific expansion of these elements in Saimiri with many active subfamilies concurrently propagating. The subset of polymorphic Alu insertions with species informative allele frequency distribution between Saimiri sciureus and Saimiri boliviensis will be instructive for specimen identification and conservation biology

Analysis of lineage-specific Alu subfamilies in the genome of the olive baboon, Papio anubis

Background: Alu elements are primate-specific retroposons that mobilize using the enzymatic machinery of L1 s. The recently completed baboon genome project found that the mobilization rate of Alu elements is higher than in the genome of any other primate studied thus far. However, the Alu subfamily structure present in and specific to baboons had not been examined yet. Results: Here we report 129 Alu subfamilies that are propagating in the genome of the olive baboon, with 127 of these subfamilies being new and specific to the baboon lineage. We analyzed 233 Alu insertions in the genome of the olive baboon using locus specific polymerase chain reaction assays, covering 113 of the 129 subfamilies. The allele frequency data from these insertions show that none of the nine groups of subfamilies are nearing fixation in the lineage. Conclusions: Many subfamilies of Alu elements are actively mobilizing throughout the baboon lineage, with most being specific to the baboon lineage

Analysis of lineage-specific Alu subfamilies in the genome of the olive baboon, Papio anubis

Background: Alu elements are primate-specific retroposons that mobilize using the enzymatic machinery of L1 s. The recently completed baboon genome project found that the mobilization rate of Alu elements is higher than in the genome of any other primate studied thus far. However, the Alu subfamily structure present in and specific to baboons had not been examined yet. Results: Here we report 129 Alu subfamilies that are propagating in the genome of the olive baboon, with 127 of these subfamilies being new and specific to the baboon lineage. We analyzed 233 Alu insertions in the genome of the olive baboon using locus specific polymerase chain reaction assays, covering 113 of the 129 subfamilies. The allele frequency data from these insertions show that none of the nine groups of subfamilies are nearing fixation in the lineage. Conclusions: Many subfamilies of Alu elements are actively mobilizing throughout the baboon lineage, with most being specific to the baboon lineage

Cross-ancestry atlas of gene, isoform, and splicing regulation in the developing human brain

INTRODUCTION Genome-wide association studies (GWASs) have identified thousands of loci associated with neurodevelopmental and psychiatric disorders, yet our lack of understanding of the target genes and biological mechanisms underlying these associations remains a major challenge. GWAS signals for many neuropsychiatric disorders, including autism spectrum disorder, schizophrenia, and bipolar disorder, are particularly enriched for gene-regulatory elements active during human brain development. However, the lack of a unified population-scale, ancestrally diverse gene-regulatory atlas of human brain development has been a major obstacle for the functional assessment of top loci and post-GWAS integrative analyses. RATIONALE To address this critical gap in knowledge, we have uniformly processed and systematically characterized gene, isoform, and splicing quantitative trait loci (cumulatively referred to as xQTLs) in the developing human brain across 672 unique samples from 4 to 39 postconception weeks spanning European, African-American, and Latino/admixed American ancestries). With this expanded atlas, we sought to specifically localize the timing and molecular features mediating the greatest proportion of neuropsychiatric GWAS heritability, to prioritize candidate risk genes and mechanisms for top loci, and to compare with analogous results using larger adult brain functional genomic reference panels. RESULTS In total, we identified 15,752 genes harboring a gene, isoform and/or splicing cis-xQTL, including 49 genes associated with four large, recurrent inversions. Highly concordant effect sizes were observed across populations, and our diverse reference panel improved resolution to fine-map underlying candidate causal regulatory variants. Substantially more genes were found to harbor QTLs in the first versus second trimester of brain development, with a notable drop in gene expression and splicing heritability observed from 10 to 18 weeks coinciding with a period of rapidly increasing cellular heterogeneity in the developing brain. Isoform-level regulation, particularly in the second trimester, mediated a greater proportion of heritability across multiple psychiatric GWASs compared with gene expression regulation. Through colocalization and transcriptome-wide association studies, we prioritized biological mechanisms for ~60% of GWAS loci across five neuropsychiatric disorders, with >2-fold more colocalizations observed compared with larger adult brain functional genomic reference panels. We observed convergence between common and rare-variant associations, including a cryptic splicing event in the high-confidence schizophrenia risk gene SP4. Finally, we constructed a comprehensive set of developmentally regulated gene and isoform coexpression networks harboring unique cell-type specificity and genetic enrichments. Leveraging this cell-type specificity, we identified >8000 module interaction QTLs, many of which exhibited additional GWAS colocalizations. Overall, neuropsychiatric GWASs and rare variant signals localized more strongly within maturing excitatory- and interneuron-associated modules compared with those enriched for neural progenitor cell types. Results can be visualized at devbrainhub.gandallab.org. CONCLUSION We have generated a large-scale, cross-population resource of gene, isoform, and splicing regulation in the developing human brain, providing comprehensive developmental and cell-type-informed mechanistic insights into the genetic underpinnings of complex neurodevelopmental and psychiatric disorders