| This month in The Journal |
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| H. Eldon Sutton, PhD (1927–2023): A long and full life |
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| Tree-based QTL mapping with expected local genetic relatedness matrices |
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| Genomic medicine year in review: 2023 |
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| Identifying risk variants for embryo aneuploidy using ultra-low coverage whole-genome sequencing from preimplantation genetic testing |
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| Improved detection of aberrant splicing with FRASER 2.0 and the intron Jaccard index |
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| The NYCKidSeq randomized controlled trial: Impact of GUÍA digitally enhanced genetic results disclosure in diverse families |
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| Increasing diversity of functional genetics studies to advance biological discovery and human health |
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| CHARR efficiently estimates contamination from DNA sequencing data |
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| Assortative mating and parental genetic relatedness contribute to the pathogenicity of variably expressive variants |
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| Bi-allelic loss-of-function variants in WBP4, encoding a spliceosome protein, result in a variable neurodevelopmental syndrome |
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| Inferring disease architecture and predictive ability with LDpred2-auto |
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| Efficient in vivo prime editing corrects the most frequent phenylketonuria variant, associated with high unmet medical need |
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| RAB1A haploinsufficiency phenocopies the 2p14–p15 microdeletion and is associated with impaired neuronal differentiation |
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| The GenoVA study: Equitable implementation of a pragmatic randomized trial of polygenic-risk scoring in primary care |
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| Response to Luzzatto et al. |
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| Potentially pathogenic and pathogenic G6PD variants |
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| To boldly go: Unpacking the NHGRI’s bold predictions for human genomics by 2030 |
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| Factorizing polygenic epistasis improves prediction and uncovers biological pathways in complex traits |
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| Envisioning a new era: Complete genetic information from routine, telomere-to-telomere genomes |
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| This month in The Journal |
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| Power of inclusion: Enhancing polygenic prediction with admixed individuals |
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| Prospective, multi-site study of healthcare utilization after actionable monogenic findings from clinical sequencing |
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| An autosomal-dominant childhood-onset disorder associated with pathogenic variants in VCP |
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| A scalable approach to characterize pleiotropy across thousands of human diseases and complex traits using GWAS summary statistics |
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| Estimating heritability explained by local ancestry and evaluating stratification bias in admixture mapping from summary statistics |
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| Identification of a robust DNA methylation signature for Fanconi anemia |
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| Rare de novo gain-of-function missense variants in DOT1L are associated with developmental delay and congenital anomalies |
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| Functional filter for whole-genome sequencing data identifies HHT and stress-associated non-coding SMAD4 polyadenylation site variants >5 kb from coding DNA |
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| The need for an intersectionality framework in precision medicine research |
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| The ancestry and geographical origins of St Helena’s liberated Africans |
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| Current and new frontiers in hereditary cancer surveillance: Opportunities for liquid biopsy |
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| Heterozygous deletion of the autism-associated gene CHD8 impairs synaptic function through widespread changes in gene expression and chromatin compaction |
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| This month in The Journal |
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| Contribution and therapeutic implications of retroelement insertions in ataxia telangiectasia |
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| Rare variants in long non-coding RNAs are associated with blood lipid levels in the TOPMed whole-genome sequencing study |
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| Frequencies of pharmacogenomic alleles across biogeographic groups in a large-scale biobank |
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| PLS3 missense variants affecting the actin-binding domains cause X-linked congenital diaphragmatic hernia and body-wall defects |
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| Literature-based predictions of Mendelian disease therapies |
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| The COPD GWAS gene ADGRG6 instructs function and injury response in human iPSC-derived type II alveolar epithelial cells |
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| Systematically testing human HMBS missense variants to reveal mechanism and pathogenic variation |
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| Demographic modeling of admixed Latin American populations from whole genomes |
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| mtPGS: Leverage multiple correlated traits for accurate polygenic score construction |
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| This month in The Journal |
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| The ancestry and geographical origins of St Helena’s liberated Africans |
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| Integration of genetic fine-mapping and multi-omics data reveals candidate effector genes for hypertension |
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| High-throughput transcriptome analyses from ASPIRO, a phase 1/2/3 study of gene replacement therapy for X-linked myotubular myopathy |
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| Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations |
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| Response to anti-IL17 therapy in inflammatory disease is not strongly impacted by genetic background |
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| Blood-based genome-wide DNA methylation correlations across body-fat- and adiposity-related biochemical traits |
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| The penetrance of rare variants in cardiomyopathy-associated genes: A cross-sectional approach to estimating penetrance for secondary findings |
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| Advanced variant classification framework reduces the false positive rate of predicted loss-of-function variants in population sequencing data |
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| Dissecting the high-resolution genetic architecture of complex phenotypes by accurately estimating gene-based conditional heritability |
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| An RNA-informed dosage sensitivity map reflects the intrinsic functional nature of genes |
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| GLA-modified RNA treatment lowers GB3 levels in iPSC-derived cardiomyocytes from Fabry-affected individuals |
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| The phenotype-genotype reference map: Improving biobank data science through replication |
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| Systematic evaluation of genome sequencing for the diagnostic assessment of autism spectrum disorder and fetal structural anomalies |
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| AXIN1 bi-allelic variants disrupting the C-terminal DIX domain cause craniometadiaphyseal osteosclerosis with hip dysplasia |
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| Integrative splicing-quantitative-trait-locus analysis reveals risk loci for non-small-cell lung cancer |
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| Genetic insights into the age-specific biological mechanisms governing human ovarian aging |
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| This month in The Journal |
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| Combined CRISPRi and proteomics screening reveal a cohesin-CTCF-bound allele contributing to increased expression of RUVBL1 and prostate cancer progression |
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| HNRNPC haploinsufficiency affects alternative splicing of intellectual disability-associated genes and causes a neurodevelopmental disorder |
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| Genome sequencing and comprehensive rare-variant analysis of 465 families with neurodevelopmental disorders |
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| Beyond the exome: What’s next in diagnostic testing for Mendelian conditions |
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| Ethical considerations when co-analyzing ancient DNA and data from private genetic databases |
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| High-throughput functional dissection of noncoding SNPs with biased allelic enhancer activity for insulin resistance-relevant phenotypes |
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| Population screening shows risk of inherited cancer and familial hypercholesterolemia in Oregon |
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| An allelic-series rare-variant association test for candidate-gene discovery |
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| Genotype error due to low-coverage sequencing induces uncertainty in polygenic scoring |
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| A form of inherited hyperferritinemia associated with bi-allelic pathogenic variants of STAB1 |
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| Monoallelic variation in DHX9, the gene encoding the DExH-box helicase DHX9, underlies neurodevelopment disorders and Charcot-Marie-Tooth disease |
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| De novo missense variants in phosphatidylinositol kinase PIP5KIγ underlie a neurodevelopmental syndrome associated with altered phosphoinositide signaling |
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| Stretch-activated ion channel TMEM63B associates with developmental and epileptic encephalopathies and progressive neurodegeneration |
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| Genetic underpinning of the comorbidity between type 2 diabetes and osteoarthritis |
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| Response to Li and Hopper |
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| Approaches to studying the impact of 22q11.2 copy number variants |
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| Multi-response Mendelian randomization: Identification of shared and distinct exposures for multimorbidity and multiple related disease outcomes |
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| Response to Bassett et al. |
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| This month in The Journal |
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| Implications of family history and polygenic risk scores for causation |
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| Polygenic risk prediction: why and when out-of-sample prediction R2 can exceed SNP-based heritability |
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| Epilepsies of presumed genetic etiology show enrichment of rare variants that occur in the general population |
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| Using the ACMG/AMP framework to capture evidence related to predicted and observed impact on splicing: Recommendations from the ClinGen SVI Splicing Subgroup |
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| High-throughput identification of regulatory elements and functional assays to uncover susceptibility genes for nasopharyngeal carcinoma |
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| Null and missense mutations of ERI1 cause a recessive phenotypic dichotomy in humans |
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| Autoimmune alleles at the major histocompatibility locus modify melanoma susceptibility |
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| CGG repeat expansion in LRP12 in amyotrophic lateral sclerosis |
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| Studying the impact of translational genomic research: Lessons from eMERGE |
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| Haplotype-based analysis resolves missing heritability in oculocutaneous albinism type 1B |
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| Extreme phenotypic heterogeneity in non-expansion spinocerebellar ataxias |
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| Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry |
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✓ |
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European ancestry |
| Actionability of unanticipated monogenic disease risks in newborn genomic screening: Findings from the BabySeq Project |
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| Progress in expanding newborn screening in the United States |
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| Response to Grosse et al. |
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| eXclusionarY: 10 years later, where are the sex chromosomes in GWASs? |
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| This month in The Journal |
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| An intronic GAA repeat expansion in FGF14 causes the autosomal-dominant adult-onset ataxia SCA27B/ATX-FGF14 |
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| Estimating clinical risk in gene regions from population sequencing cohort data |
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| Impact of cross-ancestry genetic architecture on GWASs in admixed populations |
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| Monoallelic intragenic POU3F2 variants lead to neurodevelopmental delay and hyperphagic obesity, confirming the gene’s candidacy in 6q16.1 deletions |
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| The clinical and molecular spectrum of the KDM6B-related neurodevelopmental disorder |
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| Declining autozygosity over time: An exploration in over 1 million individuals from three diverse cohorts |
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| Bi-allelic variants in HMGCR cause an autosomal-recessive progressive limb-girdle muscular dystrophy |
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| A joint transcriptome-wide association study across multiple tissues identifies candidate breast cancer susceptibility genes |
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| Genome-wide aggregated trans-effects on risk of type 1 diabetes: A test of the “omnigenic” sparse effector hypothesis of complex trait genetics |
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| The functional impact of 1,570 individual amino acid substitutions in human OTC |
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| Kurt Hirschhorn (1926–2022) |
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| This month in The Journal |
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| Comprehensive genetic and phenotype analysis of 95 individuals with mosaic tuberous sclerosis complex |
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| Genetic heritage of the Baphuthi highlights an over-ethnicized notion of “Bushman” in the Maloti-Drakensberg, southern Africa |
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| Autism-specific PTEN p.Ile135Leu variant and an autism genetic background combine to dysregulate cortical neurogenesis |
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| De novo variants implicate chromatin modification, transcriptional regulation, and retinoic acid signaling in syndromic craniosynostosis |
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| POLR1A variants underlie phenotypic heterogeneity in craniofacial, neural, and cardiac anomalies |
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| SRSF1 haploinsufficiency is responsible for a syndromic developmental disorder associated with intellectual disability |
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| Dissecting the polygenic basis of atherosclerosis via disease-associated cell state signatures |
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| Bi-allelic variants in INTS11 are associated with a complex neurological disorder |
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| Fast and accurate Bayesian polygenic risk modeling with variational inference |
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| Evidence of epistasis in regions of long-range linkage disequilibrium across five complex diseases in the UK Biobank and eMERGE datasets |
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| This month in The Journal |
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| Scalable mixed model methods for set-based association studies on large-scale categorical data analysis and its application to exome-sequencing data in UK Biobank |
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| Bi-allelic variants in the ESAM tight-junction gene cause a neurodevelopmental disorder associated with fetal intracranial hemorrhage |
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| A novel CCDC91 isoform associated with ossification of the posterior longitudinal ligament of the spine works as a non-coding RNA to regulate osteogenic genes |
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| Deletion mapping of regulatory elements for GATA3 in T cells reveals a distal enhancer involved in allergic diseases |
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| Trio RNA sequencing in a cohort of medically complex children |
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| Identifying parental and cell-division origins of aneuploidy in the human blastocyst |
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| Variants in ATRIP are associated with breast cancer susceptibility in the Polish population and UK Biobank |
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| Bi-allelic SNAPC4 variants dysregulate global alternative splicing and lead to neuroregression and progressive spastic paraparesis |
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| Robust multivariable Mendelian randomization based on constrained maximum likelihood |
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| Patterns of mosaicism for sequence and copy-number variants discovered through clinical deep sequencing of disease-related genes in one million individuals |
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| Enhancer variants on chromosome 2p14 regulating SPRED2 and ACTR2 act as a signal amplifier to protect against rheumatoid arthritis |
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| Variation in ERAP2 has opposing effects on severe respiratory infection and autoimmune disease |
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| 2022 Curt Stern Award introduction: Heidi Rehm |
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| 2022 ASHG awards and addresses |
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| 2022 Victor A. McKusick Leadership Award |
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| This month in The Journal |
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| Rare EIF4A2 variants are associated with a neurodevelopmental disorder characterized by intellectual disability, hypotonia, and epilepsy |
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| 2022 Curt Stern Award: Advancing genomic medicine through collaboration and data sharing |
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| Celebrating excellence, acknowledging past harms: Both are vital parts of ASHG’s continuing journey to advance human genetics |
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| 2022 ASHG presidential address—One human race: Billions of genomes |
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| 2022 William Allan Award |
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| Facing Our History—Building an Equitable Future |
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| On the report of the ASHG “Facing Our History—Building an Equitable Future” initiative |
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| Dynamic chromatin accessibility tuning by the long noncoding RNA ELDR accelerates chondrocyte senescence and osteoarthritis |
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| 2022 Victor A. McKusick Leadership Award introduction: David Nelson |
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| 2022 William Allan Award introduction: Peter Donnelly |
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| Australian Genomics: Outcomes of a 5-year national program to accelerate the integration of genomics in healthcare |
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| The impact of coding germline variants on contralateral breast cancer risk and survival |
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| Epigenetic regulation of plastin 3 expression by the macrosatellite DXZ4 and the transcriptional regulator CHD4 |
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| Effects of protein-coding variants on blood metabolite measurements and clinical biomarkers in the UK Biobank |
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| Development of an oral treatment that rescues gait ataxia and retinal degeneration in a phenotypic mouse model of familial dysautonomia |
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| Deficiency of primate-specific SSX1 induced asthenoteratozoospermia in infertile men and cynomolgus monkey and tree shrew models |
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| Targeted long-read sequencing of the Ewing sarcoma 6p25.1 susceptibility locus identifies germline-somatic interactions with EWSR1-FLI1 binding |
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| Inherited mutations affecting the SRCAP complex are central in moderate-penetrance predisposition to uterine leiomyomas |
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| Challenges of accurately estimating sex-biased admixture from X chromosomal and autosomal ancestry proportions |
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| Using genetic association data to guide drug discovery and development: Review of methods and applications |
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| Response to Pfenning and Lachance |
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| This month in The Journal |
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| Bi-allelic TTI1 variants cause an autosomal-recessive neurodevelopmental disorder with microcephaly |
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| The impact of 22q11.2 copy-number variants on human traits in the general population |
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| Significance tests for R2 of out-of-sample prediction using polygenic scores |
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| Loci for insulin processing and secretion provide insight into type 2 diabetes risk |
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| Functional interpretation, cataloging, and analysis of 1,341 glucose-6-phosphate dehydrogenase variants |
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| Web-accessible application for identifying pathogenic transcripts with RNA-seq: Increased sensitivity in diagnosis of neurodevelopmental disorders |
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| Comprehensive SMN1 and SMN2 profiling for spinal muscular atrophy analysis using long-read PacBio HiFi sequencing |
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| Epigenome-wide meta-analysis of BMI in nine cohorts: Examining the utility of epigenetically predicted BMI |
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| Pathogen exposure misclassification can bias association signals in GWAS of infectious diseases when using population-based common control subjects |
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| 15 years of GWAS discovery: Realizing the promise |
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| Fast, accurate local ancestry inference with FLARE |
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| Unsupervised discovery of ancestry-informative markers and genetic admixture proportions in biobank-scale datasets |
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| Bi-allelic variants in NAE1 cause intellectual disability, ischiopubic hypoplasia, stress-mediated lymphopenia and neurodegeneration |
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| Leveraging drug perturbation to reveal genetic regulators of hepatic gene expression in African Americans |
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African Americans |
| Probabilistic integration of transcriptome-wide association studies and colocalization analysis identifies key molecular pathways of complex traits |
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| Genotype first: Clinical genomics research through a reverse phenotyping approach |
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| mBAT-combo: A more powerful test to detect gene-trait associations from GWAS data |
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| This month in The Journal |
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| Deleterious, protein-altering variants in the transcriptional coregulator ZMYM3 in 27 individuals with a neurodevelopmental delay phenotype |
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| Low disease risk and penetrance in Leber hereditary optic neuropathy |
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| Is the disease risk and penetrance in Leber hereditary optic neuropathy actually low? |
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| De novo mutation hotspots in homologous protein domains identify function-altering mutations in neurodevelopmental disorders |
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| Rare EIF4A2 variants are associated with a neurodevelopmental disorder characterized by intellectual disability, hypotonia, and epilepsy |
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| Genome-wide analysis of copy-number variation in humans with cleft lip and/or cleft palate identifies COBLL1, RIC1, and ARHGEF38 as clefting genes |
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| An intronic GAA repeat expansion in FGF14 causes the autosomal-dominant adult-onset ataxia SCA27B/ATX-FGF14 |
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| LDAK-GBAT: Fast and powerful gene-based association testing using summary statistics |
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| SDPRX: A statistical method for cross-population prediction of complex traits |
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| Statistical phasing of 150,119 sequenced genomes in the UK Biobank |
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