Somatic Mosaicism, Germline Mosaicism, McCune-Albright Syndrome, Trisomy 21 Mosaicism, Osteogenesis Imperfecta Type II, Locus Heterogeneity, Allelic Heterogeneity, Pleiotropy, Variable Expressivity, Incomplete Penetrance, Hereditary Breast Cancer, Polydac

Somatic Mosaicism, Germline Mosaicism, McCune-Albright Syndrome, Trisomy 21 Mosaicism, Osteogenesis Imperfecta Type II, Locus Heterogeneity, Allelic Heterogeneity, Pleiotropy, Variable Expressivity, Incomplete Penetrance, Hereditary Breast Cancer, Polydactyly, Retinoblastoma, Fragile X Syndrome, Waardenburg Syndrome, Neurofibromatosis Type 1, Hemochromatosis, Marfan Syndrome, Cystic Fibrosis, Prader-Willi Syndrome, Angelman Syndrome, Genomic Imprinting, Maternal Imprinting, Paternal Imprinting, Uniparental Disomy, Triple Repeat Diseases, Huntington Disease, Fragile X, Friedrich Ataxia, Anticipation, Multifactorial Inheritance, Polygenic Traits, Concordance, Heritability Exam Questions Verified and Provided with A+ Graded Rationales Latest Updated 2026 Somatic mosaicism non germ cells of the body are heterogenous - some have mutations some do not (milder phenotype) Mutation arises from mitotic errors after fertilization McCune-Albright syndrome Is it a type of somatic or germline mosaicism? Somatic Mosaicism - Mutation affects G protein signaling -Lethal if mutation occurs before fertilization Presentation: - cafe au lait spots - polystotic fibers - multiple endocrine abnormalities Trisomy 21 Is it a type of somatic or germline mosaicism? Know the chromosome nomenclature! 47, +21/46 Somatic mosaicism Occurs when Nondisjunction takes place in MITOSIS rather than meiosis - Some cells have 47 chromosomes, some have the normal 46 chromosomes -Phenotype is less extreme - less than 3% of down syndrome cases What 3 things can cause down syndrome? (HY) Nondisjunction (most common) Unbalanced Robertsonian Translocation Mosaicism (least common) Which type of mosaicism can the genetic disorder be passed on to the children? Germline mosaicism Germline mosaicism Diploid germ cells precursors in gonad are heterogeneous - some have mutations some do not **CAN be passed on to offspring but parents present as NORMAL Osteogenesis Imperfecta Type II (TQ) "Brittle Bone Disease" Is it a type of somatic or germline mosaicism? Deficiency of Type I collagen (COL1A1 or COL1A2) -Type 2 is most severe *** Germline mosaicism*** Locus heterogeneity Penetrance Complete vs Incomplete Percentage of people who actually express the phenotype with corresponding genotype Complete or 100% penetrance (RARE) -Every individual will have symptom Incomplete: not all individuals w/ mutant phenotype show the mutant phenotype (most common) Expressivity What is variable expressivity the intensity of the phenotype in an individual - how much the individual expresses Variable: one genotype produces a range of phenotypes What diseases can be classified as incomplete penetrance 1. Hereditary Brest Cancer 2. Polydactyly 3. Retinoblastoma 4. Fragile X Syndrome Waardenburg Syndrome (TQ/HY) Variable Expressivity - Early family member has same genotype but shows a diff. combo of symptoms 4 principle features: - premature greying - hearing loss - white forelock - different colored eyes Disease related to Variable Expression Hemochromatosis Neurofibromatosis Type 1