Non-Mendelian Inheritance PDF

Non-Mendelian Inheritance Ozlem AKGUN-DOGAN,MD Department of Pediatrics Division of Pediatric Genetics Non-Mendelian Inheritance Exceptions for Mendelian Inheritance Epigenetics Genomic Imprinting and Imprinting Disorders Uniparental Dysomy Triple Repeat Disorders Mosaicism Mit...

Non-Mendelian Inheritance Ozlem AKGUN-DOGAN,MD Department of Pediatrics Division of Pediatric Genetics Non-Mendelian Inheritance Exceptions for Mendelian Inheritance Epigenetics Genomic Imprinting and Imprinting Disorders Uniparental Dysomy Triple Repeat Disorders Mosaicism Mitochondrial Disorders Multifactorial Inheritance Phenotypically normal family members do not transmit the phenotype to their children Exceptions: Reduced Penetrance Variable Expressivity Reduced/Incomplete Penetrance Exceptions for Mendelian Inheritance Variable Expressivity Reduced Penetrance Co-domiancy Skewed X incativation Reduced Penetrance Variable Expressivity  Variable Expressivity NF- 1 Exceptions for Mendelian Inheritance Variable Expressivity Reduced Penetrance Codominacy Skewed X incativation Codominacy Exceptions for Mendelian Inheritance Variable Expressivity Reduced Penetrance Codominacy Skewed X incativation  X linked recessive disorders Affected females … Manifesting heterozygotes (Skewed X Inactivation) Non Mendelian Inheritance Exceptions for Mendelian Inheritance Epigenetics Genomic Imprinting and Imprinting Disorders Uniparental Dysomy Triple Repeat Disorders Mosaicism Mitochondrial Disorders Multifactorial Inheritance Epigenetics Non Mendelian Inheritance Expections for Mendelian Inheritance Epigenetics Genomic Imprinting and Imprinting Disorders Uniparental Dysomy Triple Repeat Disorders Mosaicism Mitochondrial Disorders Multifactorial Inheritance Genomic imprinting  Imprinting Disorders Prader-Willi Syndrome (PWS) Angelman Syndrome (AS) Both located on the 15q11.2-13 Non Mendelian Inheritance Expections for Mendelian Inheritance Epigenetics Genomic Imprinting and Imprinting Disorders Uniparental Dysomy Triple Repeat Disorders Mosaicism Mitochondrial Disorders Multifactorial Inheritance Uniparental Disomy UPD- Imprinting Disorders UPD-AR single gene disorders Non Mendelian Inheritance Expections for Mendelian Inheritance Epigenetics Genomic Imprinting and Imprinting Disorders Uniparental Dysomy Triple Repeat Disorders Mosaicism Mitochondrial Disorders Multifactorial Inheritance Triple Repeat/Expansion Disorders Premutation Anticipation Non Mendelian Inheritance Expections for Mendelian Inheritance Epigenetics Genomic Imprinting and Imprinting Disorders Uniparental Dysomy Triple Repeat Disorders Mosaicism Mitochondrial Disorders Multifactorial Inheritance Mosaicism Somatic Mosaicism- Single Gene Disorders Gonadal Mosaicism- Single Gene Disorders Non Mendelian Inheritance Expections for Mendelian Inheritance Epigenetics Genomic Imprinting and Imprinting Disorders Uniparental Dysomy Triple Repeat Disorders Mosaicism Mitochondrial Disorders Multifactorial Inheritance Mitochondrial Disorders  Inheritance of mtDNA is maternal (oocyte mitochondrias) The mitochondrias of sperm are located in the tail part which is not included in the fertilization  Replicative Segragation Homoplasmy Heteroplasmy Replicative Segragation At cell division, mtDNAs are also replicate Replicated mitochondrias are distributed randomly between daughter cells  Homoplasmy/ Heteroplasmy Homoplasmy Heteroplasmy Daughter cell contain only a Daughter cell have a mixture pure of mitochondria, population of normal some with and some without mtDNA mutation or population of mutant mtDNA Disease Phenotype Mutation in Homoplasm Inheritance mtDNA y/ Heteroplas my Leber Rapid onset ND4 subunit of Largely Maternal Hereditary blindness complex I of homoplasmic Optic electron Neuropathy transport (LHON) NARP Neuropathy, Point mutations Heteroplasmic Maternal ataxia, dev. in ATPase Delay, mental subunit 6 gene retardation Leigh Progressive Point mutations Heteroplasmic Maternal Syndrome neurodegenarat in ATPase ion, dev. Delay, subunit 6 gene MELAS Myopathy, lactic Point mut. In Heteroplasmic Maternal acidosis, stroke tRNAleu(UUR) like episodes, MERF Myoclonic Point mut. In Heteroplasmic Maternal epilepsy, tRNAlys ragged red muscle fibers, ataxia, Deafness Progressive Mutations in Homoplasmic Maternal sensoneuronil 12S rRNA deafness Pearson Pancreatic Large Deletions Heteroplasmic Maternal for Syndrome insuf. point mut. Sporadic for deletiona Kearsn-Syre Myopathy, heart 5kb dletion Heteroplasmic Sporadic due to syndrome block, ataxia somatic mutations Non Mendelian Inheritance Expections for Mendelian Inheritance Epigenetics Genomic Imprinting and Imprinting Disorders Uniparental Dysomy Triple Repeat Disorders Mosaicism Mitochondrial Disorders Multifactorial Inheritance Multifactorial Inheritance Multifactorial Diseases Congenital malformations Common diseases congenital heart defects asthma neural tube defects schizophrenia cleft lip/palate diabetes mellitus pyloric stenosis hypertension congenital hip dysplasia