1.3 Ontology of inherited disease Chromosome disorder Single-gene disorder Mitochondrial genetic disorder Multifactorial disorder Somatic cell genetic disorder Chromosome DisorderNumerical or structural change of 1 chromosome (details in Chapter 5)7/1000 live-births; 50% spontaneous 1st trimester abortions.Examples:Down syndrome / trisomy 21Turner syndrome / monosomy XAlagille syndrome / 20p11-121.3 Ontology of Inherited disease Single Nucleotide Changes can Lead to DiseaseHbS-CCT GTG GAG-Pro Val Glu-HbA-CCT GAG GAG-Pro Glu Glu-Sickle CellSickle CellAnemiaAnemia1.3 Ontology of Inherited disease Single-gene (monogenic) DisorderAppear in families in a defined pattern, referred as Medelian pattern (details in Chapter 4)Highest 1/500, usually much less2% of total population0.36% live-births6-8% hospitalized children1.3 Ontology of Inherited disease Mitochondrial Genetic DisorderNon-Medelian patternMaternalHeteroplasmy is common 1.3 Ontology of Inherited disease Multifactorial disorder5% pediatric population; 60% whole populationFamilial clusteringNo clear Medelian patternSex difference in frequencyNo clear biochemical or molecular defectConsiderable variation in expression within and between familiesGenetic and environmental components are important (details in Chapter 7)1.3 Ontology of Inherited disease Somatic Cell Genetic DisorderNon-Medelian patternMost of them are cancersChromosomal or mitochondrial 1.3 Ontology of Inherited disease Human Development and Reproduction1.4.2 Types of Cell Division- Mitosis and Meiosis The chromosome number of normal undifferentiated somatic cells does not change during the mitotic cell cycle, the DNA content clearly does. The cell cycle comprises a very short stage of cell division, the M phase(mitosis phase) and a long intervening interphase which comprises three phases: S phase (DNA synthesis phase), G1 phase (gap between M phase and S phase) and G2 phase Mitosis: 1, prophase. 2, metaphase. 3, anaphase. 4, telophase. Meiosis I: 1, prophase I (a, leptotene stage. b, zygotene stage. c, pachytene stage. d, diplotene stage.) 2, metaphase I 3, anaphase I 4, telophase I. Meiosis II: 1, prophase II 2, metaphase II 3, anaphase II 4, telophase IIHuman gametogenesis 1.4 Medical Genetics and Human GenomeMitosisMammalian Cell Cycle(please review different phases of mitosis and meiosis)Understanding meiosis, and being able to teach meiosis to others, is essential to being a geneticist.From David H. LedbetterFrom David H. LedbetterFrom David H. LedbetterFrom David H. LedbetterFrom David H. LedbetterFrom David H. LedbetterFrom David H. LedbetterSummaryInherited disease can be classified as Inherited disease can be classified as chromosome disorder, monogenic disorder, mitochondrial genetic disorder, multifactorial disorder, somatic cell genetic disorderGenetic information replicates, recombinates and passes onto next generation through cell divisionsIndividual develops through cell differentiation that different sets of genes express at right time, right place and right amount.