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IMF-092-03-0001-en	Why can conventional karyotyping miss small changes or some cell populations?	Its resolution is limited, so most small copy changes and nucleotide variants are invisible, and cell culture can select against some cell populations.	Integrated Medical Foundations; chapter 92, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 69044f1433461384e4416c7bc89d4b71ecdcc37921f9a0bf241841d75bc4cce6; editorial review pending	imf lang::en chapter::092 module::092-03 review::pending
IMF-092-03-0002-en	Why does a normal fluorescence in situ hybridisation result not exclude other chromosomal abnormalities?	Labelled probes bind only selected DNA regions, so the assay sees only the targeted sequences.	Integrated Medical Foundations; chapter 92, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 69044f1433461384e4416c7bc89d4b71ecdcc37921f9a0bf241841d75bc4cce6; editorial review pending	imf lang::en chapter::092 module::092-03 review::pending
IMF-092-03-0003-en	Which abnormalities does chromosomal microarray generally miss despite genome-wide coverage, and why?	Because it measures copy number, it generally misses balanced rearrangements, many low-level mosaics, repeat expansions and small sequence variants.	Integrated Medical Foundations; chapter 92, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 69044f1433461384e4416c7bc89d4b71ecdcc37921f9a0bf241841d75bc4cce6; editorial review pending	imf lang::en chapter::092 module::092-03 review::pending
IMF-092-03-0004-en	Why are PCR-based assays vulnerable to false or missing results?	Their results depend on primer placement, making them vulnerable to allele dropout, contamination and unrecognised variation under primer-binding sites.	Integrated Medical Foundations; chapter 92, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 69044f1433461384e4416c7bc89d4b71ecdcc37921f9a0bf241841d75bc4cce6; editorial review pending	imf lang::en chapter::092 module::092-03 review::pending
IMF-092-03-0005-en	Why does adequate mean sequencing depth not guarantee that a variant would be detected?	Coverage is uneven: repeats, pseudogenes, high-GC regions, homologous genes and low-complexity sequence are difficult, so mean depth does not prove every base is adequately covered.	Integrated Medical Foundations; chapter 92, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 69044f1433461384e4416c7bc89d4b71ecdcc37921f9a0bf241841d75bc4cce6; editorial review pending	imf lang::en chapter::092 module::092-03 review::pending
IMF-092-03-0006-en	What can long-read sequencing resolve that short-read sequencing struggles with?	Long reads span larger structures, repeats, methylation and haplotypes, whereas short reads struggle to phase distant variants and resolve long repeats or rearrangements.	Integrated Medical Foundations; chapter 92, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 69044f1433461384e4416c7bc89d4b71ecdcc37921f9a0bf241841d75bc4cce6; editorial review pending	imf lang::en chapter::092 module::092-03 review::pending
IMF-092-03-0007-en	Why can RNA sequencing of blood fail to show the consequence of a DNA variant?	It depends on expression in the sampled tissue and on transcript stability; nonsense-mediated decay may erase the abnormal transcript, and blood may not show muscle- or brain-specific isoforms.	Integrated Medical Foundations; chapter 92, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 69044f1433461384e4416c7bc89d4b71ecdcc37921f9a0bf241841d75bc4cce6; editorial review pending	imf lang::en chapter::092 module::092-03 review::pending
IMF-092-03-0008-en	Why may a predicted loss-of-function variant not actually cause disease?	A stop near the gene end may escape decay, the exon may be alternatively skipped, a splice variant may preserve frame, or the gene may tolerate haploinsufficiency.	Integrated Medical Foundations; chapter 92, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 69044f1433461384e4416c7bc89d4b71ecdcc37921f9a0bf241841d75bc4cce6; editorial review pending	imf lang::en chapter::092 module::092-03 review::pending
IMF-092-03-0009-en	Why does finding a variant in an unaffected relative weaken but not refute disease association?	If penetrance is incomplete, carriers can remain unaffected, so an unaffected carrier does not disprove the association.	Integrated Medical Foundations; chapter 92, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 69044f1433461384e4416c7bc89d4b71ecdcc37921f9a0bf241841d75bc4cce6; editorial review pending	imf lang::en chapter::092 module::092-03 review::pending
IMF-092-03-0010-en	Why should a variant of uncertain significance not drive irreversible predictive or surgical decisions?	Its disease association is unresolved, and it can be reclassified as population data, family studies, functional evidence or disease knowledge grow, so patients need a plan for review.	Integrated Medical Foundations; chapter 92, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 69044f1433461384e4416c7bc89d4b71ecdcc37921f9a0bf241841d75bc4cce6; editorial review pending	imf lang::en chapter::092 module::092-03 review::pending
IMF-092-03-0011-en	Why does variant allele fraction in tumour testing not simply indicate zygosity?	It also reflects tumour purity, copy number, clonality and heterogeneity, and clonal haematopoiesis can contaminate blood or cell-free DNA and mimic tumour or germline findings.	Integrated Medical Foundations; chapter 92, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 69044f1433461384e4416c7bc89d4b71ecdcc37921f9a0bf241841d75bc4cce6; editorial review pending	imf lang::en chapter::092 module::092-03 review::pending
IMF-092-03-0012-en	Why is cell-free DNA testing in maternal plasma a screening rather than a diagnostic test?	Placental mosaicism, maternal variants, vanished twin, malignancy and low fetal fraction affect results, and positive predictive value depends strongly on prior probability.	Integrated Medical Foundations; chapter 92, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 69044f1433461384e4416c7bc89d4b71ecdcc37921f9a0bf241841d75bc4cce6; editorial review pending	imf lang::en chapter::092 module::092-03 review::pending
IMF-092-03-0013-en	How do analytical validity, clinical validity and clinical utility differ?	Analytical validity asks whether the assay detects the variant accurately, clinical validity whether the variant predicts phenotype, and clinical utility whether the result improves decisions or outcomes.	Integrated Medical Foundations; chapter 92, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 69044f1433461384e4416c7bc89d4b71ecdcc37921f9a0bf241841d75bc4cce6; editorial review pending	imf lang::en chapter::092 module::092-03 review::pending
IMF-092-03-0014-en	Why do underrepresented groups receive more uncertain genomic results?	Bias enters through reference genomes, training data, variant databases and ancestry imbalance, so these groups get more uncertain results and lower risk-score accuracy.	Integrated Medical Foundations; chapter 92, TTS module 3; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 69044f1433461384e4416c7bc89d4b71ecdcc37921f9a0bf241841d75bc4cce6; editorial review pending	imf lang::en chapter::092 module::092-03 review::pending