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IMF-092-01-0001-en	Why is an inheritance pattern alone insufficient for accurate reasoning about a genetic disease?	Inheritance describes only transmission, not mechanism or severity, so the molecular alteration, chromosome context, parental origin, cell distribution and phenotype must also be defined.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending
IMF-092-01-0002-en	Why must genomic coordinates state the reference assembly version?	Genomic coordinates refer to a reference assembly, and positions change between references, so a coordinate without its version is ambiguous.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending
IMF-092-01-0003-en	How do the gametes produced by nondisjunction in meiosis one differ from those produced by an error in meiosis two?	Meiosis-one nondisjunction gives gametes with both homologues or neither, whereas a meiosis-two error gives both sister chromatids or neither; fertilisation can then produce trisomy or monosomy.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending
IMF-092-01-0004-en	What does nondisjunction after fertilisation produce, and what most directly determines the resulting phenotype?	Mitotic nondisjunction after fertilisation creates mosaicism; phenotype depends more immediately on the chromosome involved, mosaic fraction, tissue distribution and dosage-sensitive genes than on meiotic origin.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending
IMF-092-01-0005-en	Why does the risk of maternal meiotic aneuploidy rise with age?	Oocytes remain arrested for a long time and their cohesion deteriorates, and errors in cohesion cause aneuploid gametes.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending
IMF-092-01-0006-en	By what routes can triploidy arise, and what does the parental origin of the chromosome sets influence?	Triploidy can result from two sperm fertilising one oocyte or from a diploid gamete, and parental origin influences the placental and fetal pattern.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending
IMF-092-01-0007-en	Why can a healthy carrier of a balanced rearrangement still face genetic consequences?	Although there is no major net copy-number change, the rearrangement can disrupt a gene or regulatory domain and can create unbalanced gametes that alter dosage.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending
IMF-092-01-0008-en	Why is parental chromosome analysis important when trisomy arises from a Robertsonian translocation?	A carrier parent can produce gametes leading to miscarriage or translocation trisomy, so family recurrence differs from that of free trisomy.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending
IMF-092-01-0009-en	How can an unaffected inversion carrier produce abnormal chromosomal products?	Recombination within the inversion loop can yield abnormal products even though the carrier's own inversion causes no disease.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending
IMF-092-01-0010-en	In autosomal-dominant disease, what can produce an isolated case or an apparently skipped generation?	A de novo variant can cause an isolated case, and reduced penetrance can make a generation appear skipped despite vertical transmission.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending
IMF-092-01-0011-en	By which mechanisms can a single altered allele cause dominant disease?	Haploinsufficiency, dominant-negative interference, gain of function, or a toxic product.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending
IMF-092-01-0012-en	Why does consanguinity raise the risk of autosomal-recessive disease?	Disease usually requires pathogenic variants in both gene copies, and consanguinity raises the chance that both parents share the same rare allele.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending
IMF-092-01-0013-en	How can an autosomal-recessive condition show vertical, apparently dominant transmission?	Pseudodominance occurs when an affected person has children with a carrier in a population where the allele is frequent.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending
IMF-092-01-0014-en	Why can heterozygous females be symptomatic in X-linked recessive disease?	Skewed X inactivation, dosage, tissue distribution, or disorders in which carriers are intrinsically affected can all produce symptoms.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending
IMF-092-01-0015-en	In X-linked dominant conditions, how does transmission from an affected father differ from that of a heterozygous mother?	An affected father transmits the variant to all daughters and no sons, while a heterozygous mother has a one-half risk of transmitting it to each child.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending
IMF-092-01-0016-en	Why can siblings who inherit the same mitochondrial variant from their mother differ in severity?	In heteroplasmy normal and variant genomes coexist; the oogenesis bottleneck, random segregation and tissue thresholds change the proportion and its effect in each child and organ.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending
IMF-092-01-0017-en	By what two routes can uniparental disomy cause disease?	Because both homologues come from one parent, it can cause imprinting disease, since expression is parent-of-origin specific, or unmask a recessive variant.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending
IMF-092-01-0018-en	What explains anticipation in unstable repeat-expansion disorders?	Repeat size may expand during gametogenesis, sometimes with parent-of-origin effects, so onset becomes earlier or severity greater across generations.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending
IMF-092-01-0019-en	What distinguishes penetrance from expressivity?	Penetrance is the proportion of people with a genotype who show a defined phenotype by a specified age; expressivity is the degree or pattern of phenotype among those affected.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending
IMF-092-01-0020-en	Why may a penetrance estimate from a referral clinic not apply to population screening?	Penetrance is influenced by ascertainment and phenotype definition, so an estimate from a selected referral population cannot be transferred directly to the general population.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending
IMF-092-01-0021-en	What distinguishes locus heterogeneity, allelic heterogeneity and phenocopy?	Locus heterogeneity is different genes causing a similar phenotype; allelic heterogeneity is different variants in one gene causing different or overlapping phenotypes; phenocopy is a similar phenotype of non-genetic cause.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending
IMF-092-01-0022-en	How can unaffected parents have more than one child with an apparently de novo variant?	Gonadal mosaicism means only a subset of the parent's cells carries the variant, so it can be transmitted repeatedly while the parent remains unaffected; low-level mosaicism may be missed in blood.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending
IMF-092-01-0023-en	In Bayesian pedigree reasoning, why may a negative test or unaffected status at a young age lower risk less than expected?	A negative result reduces risk only according to assay sensitivity and whether the familial variant is known, and unaffected status at a young age is weak evidence for late-onset disease.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending
IMF-092-01-0024-en	How can a one-half transmission risk coexist with a much lower risk of disease?	The chance of inheriting a variant and the chance of developing the phenotype are not interchangeable; under incomplete penetrance, disease risk can be much lower than transmission risk.	Integrated Medical Foundations; chapter 92, TTS module 1; https://theisegoria.github.io/medical-textbook/integrated-medical-foundations-expanded-english.md; module SHA256 at export: 788b17e2d98e9d91483858b8d0ad1605aedc90a3c264fe4d87b724ef84914e8d; editorial review pending	imf lang::en chapter::092 module::092-01 review::pending