{"artifact":{"id":"experiment-exp-wiki-experiments-tmem106b-genetic-modifier-ftd","artifact_type":"experiment","entity_ids":null,"title":"TMEM106B Haplotype as Genetic Modifier in FTD — Mechanism and Therapeutic Exploitation","quality_score":0.675,"created_by":"crosslink-v2","provenance_chain":null,"content_hash":null,"metadata":{"source":{"type":"manual","source_name":"wiki","extracted_by":"backfill_v1","extraction_date":"2026-04-16T01:00:16.905712Z"},"summary":"# TMEM106B Haplotype as Genetic Modifier in FTD — Mechanism and Therapeutic Exploitation\n## Background and Rationale\nValidation experiment to elucidate how the TMEM106B protective haplotype modifies FTD disease course, with implications for therapeutic target identification.\n\n**Protocol**: (1) CRISPR-engineered iPSC lines: isogenic GRN+/- (FTD risk) with either TMEM106B risk or protective haplotype (4 lines total). Differentiate to cortical neurons, microglia, and astrocytes. (2) Multi-omic prof","entities":{"genes":["TMEM106B"],"diseases":["Neurodegeneration"]},"model_system":"human","_schema_version":1,"experiment_type":"validation","primary_outcome":"Lysosomal function restoration by TMEM106B protective haplotype in GRN-deficient neurons","methodology_notes":"**Phase 1: Patient Cohort Assembly and Genetic Characterization (Months 1-6)**\n• Recruit n=500 FTD patients with confirmed pathogenic mutations (C9orf72, MAPT, GRN) and n=500 age-matched controls\n• Extract genomic DNA from peripheral blood samples using Qiagen QIAamp DNA Blood Maxi Kit\n• Perform whole genome sequencing (30x coverage) on Illumina NovaSeq 6000 platform\n• Genotype TMEM106B rs1990622 and rs3173615 variants using TaqMan assays in triplicate\n• Construct TMEM106B haplotypes (protective vs. risk) based on linkage disequilibrium patterns\n• Collect detailed clinical phenotyping including age of onset, disease duration, CDR-FTLD scores\n\n**Phase 2: Functional Mechanism Investigation (Months 7-18)**\n• Generate iPSC lines from n=24 FTD patients (12 protective haplotype, 12 risk haplotype)\n• Differentiate iPSCs to cortical neurons using dual SMAD inhibition protocol (21-day protocol)\n• Perform TMEM106B protein quantification via Western blot and immunofluorescence microscopy\n• Measur","replication_status":"single_study","extraction_metadata":{"backfill_at":"2026-04-16T01:00:16.905718","needs_review":true,"extraction_notes":"Backfilled from wiki source (no PMID 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