Katerina Trajanoska et al. report a genome-wide association study of self-reported falls in UK Biobank participants. They identify three novel fall-associated loci and find that risk of falling shows patterns of polygenic inheritance and a SNP-based heritability of 2.7%.
Editor's Picks in Genetics from Communications Biology
In this collection, we celebrate the diversity of genetics and genomics research published this year in Communications Biology. Explore research articles below and read Behind the Paper blog posts from our authors on the blogs page. To learn more about this collection and Communications Biology, see the About this Collection page.
A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis
Gen Sobue, Masao Nagasaki and colleagues report a genome-wide association study for amyotrophic lateral sclerosis (ALS) in a large, multi-ethnic cohort comprising Japanese, Chinese, and European ancestry populations. They find a significant association to variants within the ACSL5 gene and identify novel associations with 4 additional genes using a gene-based approach.
Akira Meguro et al. report a genome-wide association study for sarcoidosis—a systemic inflammatory disease—in the Japanese population. They identify 3 non-HLA loci with genome-wide significance, 2 of which have not been previously associated with sarcoidosis in any population.
Benjamin Simpson et al. use publicly available cancer genomic data to investigate copy number changes at the 3q26.31–32 locus, which has been associated with aggressive prostate cancer based on single-nucleotide polymorphisms. They find that gains of NAALADL2 and TBL1XR1 in this locus are associated with more aggressive subtypes of prostate cancer and the transcription of pro-proliferative signalling processes.
Keratoconus-susceptibility gene identification by corneal thickness genome-wide association study and artificial intelligence IBM Watson
Yoshikatsu Hosoda et al. study the genetic basis for central corneal thickness (CCT) that is associated with keratoconus. They identify two susceptibility loci, STON2 rs2371597 and SMAD3 rs12913547, using two-step genome-wide association study (GWAS) and predictive analysis with IBM’s Watson question answering computer system, respectively.
Analysis of genetically independent phenotypes identifies shared genetic factors associated with chronic musculoskeletal pain conditions
Yakov Tsepilov, Maxim Freidin et al. find that chronic musculoskeletal pain conditions at four distinct anatomical sites share a common genetic background. The authors constructed genetically independent phenotypes (GIP) from principal components analysis of the different pain phenotypes and used the GIPs to perform genome-wide association studies to identify underlying genetic factors.
A multiethnic genome-wide analysis of 44,039 individuals identifies 41 new loci associated with central corneal thickness
Hélène Choquet et al. report the largest genome-wide analysis of central corneal thickness (CCT) to date, finding novel associations at 41 loci. The study, which includes individuals from 4 ethnic groups, including African Americans and Hispanic/Latino individuals, increases the variance explained for CCT from 8.5% to 14.2%. Study findings also suggest that thinner CCT does not causally increase the risk of primary open-angle glaucoma.
Genome-wide association study of Buruli ulcer in rural Benin highlights role of two LncRNAs and the autophagy pathway
Jeremy Manry, Quentin Vincent et al. report a genome-wide association study for susceptibility to Buruli ulcer in a rural population from the West African country of Benin. They identify two independently associated variants within LncRNA genes and confirm the protective effect of a missense variant in the bacterial autophagy gene ATG16L1.
Gudjon Oskarsson et al. report a genome-wide association study of hemoglobin concentration in more than 680,000 individuals from Iceland and the UK. They identify six novel rare coding variants at the ACO1 locus that associate with either increased or decreased hemoglobin concentration, two of which have large and opposite effects.
Bacterial genome-wide association study of hyper-virulent pneumococcal serotype 1 identifies genetic variation associated with neurotropism
Using a genome-wide association study approach, Chaguza et al. identify significant genotype-phenotype associations relevant to Streptococcus pneumoniae infection. These findings indicate genetic variations in the pathogen attributed to pneumococcal tropism to central nervous system tissues, with implications for meningitis virulence.
Diverse panicle architecture results from various combinations of Prl5/GA20ox4 and Pbl6/APO1 alleles
Ayumi Agata et al. study the molecular mechanisms regulating panicle length which directly affects crop yield. They identify QTLs Prl5 and Pbl6 that independently regulate panicle length in rice at the gene expression level. By designing different allelic combinations, they generate desired panicle architecture and confirm their positive effect on yield in the field.
Kelly Houston et al. report a genome-wide association study for sodium content in barley to find genetic variants that may improve yield under low soil K + levels. They identify variants of the Na+ transporter-encoding gene HvHKT1;5 as important for sodium content variation in non-saline conditions.
Effect direction meta-analysis of GWAS identifies extreme, prevalent and shared pleiotropy in a large mammal
Xiang et al. developed an Effect Direction Meta-analysis (EDME) approach to identify true pleiotropy. They used Cholesky-transformation to decorrelate the traits and identified many pleiotropic variants that consistently predicted phenotypic differences in cattle.
Multi-level evidence of an allelic hierarchy of USH2A variants in hearing, auditory processing and speech/language outcomes
Peter Perrino et al. identify variants in USH2A linked to a dominant language disorder in a human family and find that these variants are also associated with low-frequency hearing at the population level. They investigate the function of USH2A variants in mice, showing that mutations in this gene are responsible for hearing loss.
The reliability and heritability of cortical folds and their genetic correlations across hemispheres
Fabrizio Pizzagalli et al. study the genetics factors that regulate cortical folding patterning in the brain. They use in vivo brain MRI datasets from around the world and report the reliability and heritability of sulcal morphometric characteristics for 61 sulci per hemisphere of the human brain. They uncover hemisphere-specific genetic influences on the cerebral cortex.
Evolution and Population Genomics
A novel WD40-repeat protein involved in formation of epidermal bladder cells in the halophyte quinoa
Tomohiro Imamura et al. report that a WD40 protein REBC, which differs from the trichome formation-linked WD40 protein TTG1, plays a critical role in epidermal bladder cell formation in quinoa. They further reveal a protective role of the epidermal bladder cells against the shoot apex damage by abiotic stress, especially salt stress, shedding light on the mechanisms underlying epidermal bladder cell formation and function.
Wireworm (Coleoptera: Elateridae) genomic analysis reveals putative cryptic species, population structure, and adaptation to pest control
Andrews et al. sequenced and assembled the genome of a wireworm, or click beetle (Limonius californicus), an agricultural pest. Their data suggest the presence of multiple genetically distinct cryptic species in addition to population structure and a local adaptive response to pesticide use.
Multiple ancestral haplotypes harboring regulatory mutations cumulatively contribute to a QTL affecting chicken growth traits
Yuzhe Wang, Xuemin Cao et al. report the fine-mapping of a major growth trait QTL in chicken using genome-wide association and haplotype association analyses. They discover multiple mutations cumulatively contribute to the previously-reported QTL and identify one of a regulatory mutation that contributes to the variation in the measured traits.
Mudd et al. provide chromosome-scale genome assemblies for the Chinese and Indian muntjac deer and demonstrate evidence for rapid evolution of genes involved in chromosome maintenance. Their comparative analyses generate new insights into rapid karyotype evolution.
Comparative genomics of muskmelon reveals a potential role for retrotransposons in the modification of gene expression
Ryoichi Yano et al. report a Nanopore-based reference genome assembly of muskmelon—a fruit known for its many cultivated varieties, including cantaloupe and honeydew—using the Japanese Harukei-3 cultivar. They identify structural genetic variation by comparing the reference to several melon genome assemblies and investigate tissue-wide gene expression patterns by RNA sequencing.
Genomic analyses of a livestock pest, the New World screwworm, find potential targets for genetic control programs
Maxwell Scott et al. report the genome of the New World screwworm, a devastating livestock pest in South America and the Caribbean. Using transcriptomic analysis of the insect’s developmental stages combined with genomic analyses, the authors identify genes that may be important for its parasitic lifestyle.
Ancient Jomon genome sequence analysis sheds light on migration patterns of early East Asian populations
Takashi Gakuhari, Shigeki Nakagome et al. report the genomic analysis on a 2.5 kya individual from the ancient Jomon culture in present-day Japan. Phylogenetic analysis with comparison to other Eurasian sequences suggests early migration patterns in Asia and provides insight into the genetic affinities between peoples of the region.
Genomic epidemiology of animal-derived tigecycline-resistant Escherichia coli across China reveals recent endemic plasmid-encoded tet(X4) gene
Sun et al. analyse E. coli strains from pigs and chickens in Chinese farms and slaughterhouses, and reveal that while the tet(X4) gene is not ubiquitous across China, it is highly endemic in northwestern China. Genomic analysis of these strains shows recent and independent acquisitions of plasmids in across regions.
Sara Lado et al. report a fine-scale analysis of genetic diversity in dromedary species across Asia and Africa. Using a genome-wide approach, the authors are able to infer patterns of migration following domestication, which follow known historic caravan routes, and identify major population expansions and bottlenecks through history.
He, Li, and Lv et al. took a genomics approach to study innate feeding behavior in mandarin fish. They identify genes related to predatory feeding that underwent rapid adaptive evolution. They also functionally validate the role of bmp4-edar pathway in inducing predatory feeding in zebrafish.
Sequence-based genetic mapping of Cynodon dactylon Pers. reveals new insights into genome evolution in Poaceae
Tilin Fang et al. study the genome of Bermudagrass (Cynodon dactylon Pers.). They use genotyping-by-sequencing and provide a genetic map with a 10-fold increase in genetic marker density. Comparative genomics analyses reveal chromosome rearrangements. Their work will contribute to whole genome assembly efforts which will be beneficial for developing new cultivars.
The genome of pest Rhynchophorus ferrugineus reveals gene families important at the plant-beetle interface
Khaled Michel Hazzouri et al. study the red palm weevil, Rhynchophorus ferrugineus, which causes agricultural damage. They provide a genome assembly and report duplications of detoxifying and insecticide resistance genes as well as genes under positive selection like the glycosyl hydrolyase gene family. Their work provides genetic insights that can help control this pest.
Robert R. Fitak et al. investigate the genetic basis for domestication in camels. They found that the positive selection of candidate domestication genes is consistent with neural crest deficiencies and altered thyroid hormone-based signaling. Their work provides insights to the evolutionary history of camels and genetics of domestication.
Whole-genome sequencing of 128 camels across Asia reveals origin and migration of domestic Bactrian camels
Ming, Yuan et al. performed whole-genome sequencing on 128 wild and domesticated Bactrian camels across Asia. They show that wild and domestic Bactrian camels are genetically diverged from dromedaries, and that wild camels contributed little to domestic camel ancestry despite sharing a habitat in East Asia.
Smith et al. compare the genomes of 130 clinical Staphylococcus pseudintermedius isolates from dogs and cats in the New England region of the United States with those from a Texas population. They find clonal expansion of methicillin-resistant S. pseudintermedius lineages over large distances, which suggests the diversification of a common cutaneous colonizer of man’s companion animals.
Genomic Resources and Methods
Samarakoon et al. present Genopo, a portable toolkit for analysis of nanopore sequencing data on Android smartphone and tablet devices. Genopo enables field-based nanopore analysis using widely accessible technology.
Highly efficient gene transfer in the mouse gut microbiota is enabled by the Incl2 conjugative plasmid TP114
Kevin Neil et al. quantified horizontal gene transfer rates for 13 conjugative plasmids in the mouse gut microbiota to identify those that might be useful for developing microbiome editing technologies. They find that the Incl-family plasmid TP114 has a nearly 100% transfer efficiency in the mouse gut.
Chemically induced mutations in a MutaMouse reporter gene inform mechanisms underlying human cancer mutational signatures
Marc A. Beal, Matt J. Meier et al. use a transgenic rodent model with NGS to inform mutational signature analyses. They analyze lacZ mutations from the bone marrow of MutaMouse animals exposed to chemical mutagens. They report that lacZ sequencing generates chemical-specific mutation signatures observed in human cancers with established environmental causes.
Improvement of CRISPR/Cas9 system by transfecting Cas9-expressing Plasmodium berghei with linear donor template
Shinzawa et al. develop a method that improves the transfection efficiency for Plasmodium parasites that cause malaria by transfecting Cas9-expressing parasites with linear donor templates. This method allows efficient integration of the donor template while preventing unexpected recombination.
Detecting protein and post-translational modifications in single cells with iDentification and qUantification sEparaTion (DUET)
Yandong Zhang, et al. develop iDentification and qUantification sEparaTion (DUET) to quantify target protein and its post-translational modification isoforms in single cells. Using their method, they report heterogeneities in the ubiquitination levels of histone H2B in single yeast cells and reveal the cell-cycle dynamics of H2B monoubiquitination.
MethylResolver—a method for deconvoluting bulk DNA methylation profiles into known and unknown cell contents
Douglas Arneson et al. develop MethylResolver that enables the deconvolution of cellular fractions from bulk DNA methylation data. Using this method, the authors resolve tumor purity-scaled immune cell-type fractions without requiring cancer-specific signatures and identify cellular fractions as prognostic factors of multiple human cancers.
Improving the diversity of captured full-length isoforms using a normalized single-molecule RNA-sequencing method
Hu et al. combine cDNA normalization before library preparation with a software tool to increase the capture of RNA isoform species in single-molecule RNA sequencing. They demonstrate that this approach can detect previously unknown transcripts in gastric signet-ring cell carcinomas that are not present in non-malignant tissue.
Krieg et al. describe a methanol responsive polymer that can capture complementary DNA using grafted oligonucleotides. They successfully demonstrate its efficacy with simultaneous and sequence-specific isolation of three target genes (cDNA) from clinical NGS libraries with high efficiency. This method is fast, effective, scalable, modular, and versatile.
Successful delivery of large-size CRISPR/Cas9 vectors in hard-to-transfect human cells using small plasmids
Søndergaard et al. show that electroporation and lipofectamine-based cell transfection of cancer cell lines and primary cells can be improved by adding a small vector to a large CRISPR vector. This study presents an optimized protocol for genome engineering by increasing transfection efficiency and cell viability.
Digital multiplex ligation assay for highly multiplexed screening of β-lactamase-encoding genes in bacterial isolates
Tamminen et al. develop a digital multiplex ligation assay (dMLA) that enables the detection of bacterial isolates using probe hybridization and ligation-based assays with next-generation sequencing. Their method can be applied in high-throughput and affordable screening for antibiotic resistance.
Maeve O’Huallachain et al. report a method that enables simultaneous, ultra-high throughput single-cell barcoding for targeted single-cell protein and RNA analysis. They show the utility of their method in analyses of mRNA and protein expression in human and mouse cells.
Single-cell analysis of a mutant library generated using CRISPR-guided deaminase in human melanoma cells
Jun, Lim et al. combined CRISPR RNA-guided deaminase and single-cell RNA sequencing technology to functionally discriminate the target mutations from off-target mutations. This study provides a platform that allows researchers to generate multiple mutations and to screen the cells that contain the target mutations in a high-throughput manner.
Development of a CRISPR/Cas9n-based tool for metabolic engineering of Pseudomonas putida for ferulic acid-to-polyhydroxyalkanoate bioconversion
Yueyue Zhou et al. develop a genetic engineering method that increases the production of polyhydroxyalkanoate from ferulic acid, which is toxic at high concentrations. This study provides insight into the bioconversion of the aromatic compound in Pseudomonas.
CRISPR/Cas12a technology combined with immunochromatographic strips for portable detection of African swine fever virus
Wang et al. developed a method to detect the African Swine Fever Virus on site using CRISPR/Cas12a technology and lateral flow detection. This method is portable, sensitive and specific for ASFV and can help in controlling ASFV outbreak.
Xiaobao Dong et al. developed a network-based framework to measure cancer diversity for cancer driver mutations, finding that half of driver genes contain both cancer type-specific and pancancer mutations. They show that the specificity of mutations could influence therapeutic responses.
Multi-omics and Functional Genomics
Analysis of single-cell transcriptomes links enrichment of olfactory receptors with cancer cell differentiation status and prognosis
Through analyses of olfactory receptors in single-cell RNA sequencing dataset from different cancers, Kalra, Mittal et al. find that the number and expression levels of olfactory receptors vary by differentiation status. The study provides insights into an under-appreciated role for olfactory receptors in cancer pathogenesis.
Wang et al. perform RNA-Seq on pineapple floral samples and also use previously published RNA-Seq datasets to generate tissue- and stage-specific transcriptomic profiles. The authors use weighted gene co-expression network analysis to identify gene networks, bringing insight to underlying pineapple reproductive organ growth.
Through shallow single-cell sequencing of genomic DNA followed by clustering analysis, Velazquez-Villarreal et al. reveal sub-clones of the melanoma cell line COLO829 and further identify and validate chromosome translocations and copy number changes. This study illustrates how copy number variation analysis can provide insights into cancer cell heterogeneity.
Habowski et al. develop a sorting protocol for purification and comparative analysis of mouse colon stem cells and their progeny. By proteomic and transcriptomic analysis, they determine that lineage commitment is accompanied by a greater change in mRNA splicing and polyadenylation than in gene expression and they characterise signalling pathways involved in differentiation.
Fulya Akçimen et al. report a transcriptome-wide association study of restless legs syndrome using publicly available data from genome-wide association studies and gene expression data from GTEx. They find significant associations at 8 loci, 6 of which are novel and one of which implicates dopaminergic pathway.
Cell-to-cell expression dispersion of B-cell surface proteins is linked to genetic variants in humans
Triqueneaux, Burny, Symmons et al. show association between gene expression noise and genotypes, using single-cell expression of four proteins across human-derived lymphoblastoid cell lines. This study suggests that very subtle regulatory effects of human DNA variants may contribute to phenotypic variation and disease outcome.
Alma Andersson et al. present a probabilistic framework that integrates single-cell and bulk spatial transcriptomics in order to spatially map cell types onto their respective tissues. They apply their method to the developing human heart and mouse brain to demonstrate the power of the technique.
Mutually suppressive roles of KMT2A and KDM5C in behaviour, neuronal structure, and histone H3K4 methylation
Vallianatos et al. study the functional interactions of KMT2A and KDM5C, H3K4me enzymes known to be involved in neurodevelopmental disorders. Using genetic mouse models, neuronal structure analysis, neurobehavior, and epigenomic profiling, they demonstrate a mutually suppressive relationship between KMT2A and KDM5C during neurodevelopment.
Golicz et al. report an increase in single nucleotide polymorphisms and structural variations across and within Topologically Associated Domains (TADs) in the rice genome, which is different to the pattern observed in the human genome. They show that this may be due to epigenetic modifications, transposable elements composition, and meiotic crossovers in the TAD regions.
Single-cell expression and Mendelian randomization analyses identify blood genes associated with lifespan and chronic diseases
Arnaud Chignon et al. present an integrated analysis of single-cell expression data from blood and genome-wide studies to identify expressed genes (eGenes) associated with human lifespan. The 125 eGenes identified are enriched for cardiometabolic traits and disorders and 16 are causally related to lifespan, as shown by Mendelian Randomization analysis.
Solé-Boldo et al characterise dermal fibroblasts in human skin not exposed to sunlight by single-cell RNA sequencing. They identify fibroblast subpopulations and see that aging reduces their identity and predicted interactions with other skin cells, providing insights into age-related changes in skin.
Single-cell RNA sequencing reveals a heterogeneous response to Glucocorticoids in breast cancer cells
Hoffman et al characterise the transcriptional response to glucocorticoids in single breast cancer cells in culture. They discover a heterogeneous response and identify over 100 target genes not detected by bulk RNA sequencing, illustrating the power of single cell sequencing and informing on the hormone response in breast cancer.
Gene expression variation in the brains of harvester ant foragers is associated with collective behavior
Friedman et al. examine gene expression in the brains of red harvester ant foragers. They show that colonies differ from each other in the expression of neurophysiologically-relevant genes, and that natural selection may shape colony foraging behavior by acting on this variation among colonies in gene expression.
Sergey A. Shmakov et al. investigate the origin of the CRISPR spacers. They examine the distribution of partial matches between the spacers, viral genomes, and the host genomes and report that most of the spacers originate from host specific viromes. They demonstrate that most of the viruses are unknown although are likely related to known viruses.
Reciprocal H3.3 gene editing identifies K27M and G34R mechanisms in pediatric glioma including NOTCH signaling
Kuang-Yui Chen et al. show that histone H3.3 K27M and G34R mutations share key oncogenic mechanisms such as activation of neurogenesis and NOTCH pathway genes. They find that H3.3 mutant gliomas are sensitive to inhibition of the NOTCH pathway, suggesting a potentially targetable pathway in pediatric gliomas.