* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Introduction to Inheritance - Goring & Woodcote Medical Practice
Survey
Document related concepts
Nutriepigenomics wikipedia , lookup
Genetic testing wikipedia , lookup
Biology and consumer behaviour wikipedia , lookup
History of genetic engineering wikipedia , lookup
Population genetics wikipedia , lookup
Behavioural genetics wikipedia , lookup
Fetal origins hypothesis wikipedia , lookup
Designer baby wikipedia , lookup
Microevolution wikipedia , lookup
Birth defect wikipedia , lookup
Transgenerational epigenetic inheritance wikipedia , lookup
Neuronal ceroid lipofuscinosis wikipedia , lookup
Epigenetics of neurodegenerative diseases wikipedia , lookup
Tay–Sachs disease wikipedia , lookup
Medical genetics wikipedia , lookup
Genome (book) wikipedia , lookup
Transcript
Introduction to Inheritance Sara Levene Registered Genetic Counsellor London IDEAS Genetic Knowledge Park Mendelian Genetics Genetic conditions are not very common Disease Cystic fibrosis (in Caucasians of North-western European origin) Cystic fibrosis carriers Huntington disease (higher in UK) Duchenne muscular dystrophy Incidence 1/2500 1/25 1/14000 1/3500 males Inheritance Patterns Autosomal dominant (AD) Autosomal recessive (AR) X-Linked (X-L) Dominant Inheritance Dominant Inheritance Common Autosomal Dominant Disorders Huntington Disease Marfan syndrome Myotonic dystrophy Neurofibromatosis Breast / ovarian cancer susceptibility (BRCA1/2) Familial Adenomatous polyposis Hereditary Non-Polyposis Colorectal cancer (HNPCC) Recessive Inheritance Non carrier Carrier Carrier Affected individual Recessive Inheritance Common Autosomal Recessive Disorders Cystic Fibrosis Sickle cell anaemia Thalassaemia Tay Sachs disease Spinal muscular atrophy PKU Haemachromatosis X-Linked Inheritance Non carrier girl Non carrier boy Carrier girl Affected boy X-Linked Inheritance Common X-Linked Disorders Duchenne muscular dystrophy Becker muscular dystrophy Haemophilia Fragile X syndrome Multifactorial Inheritance Multifactorial Inheritance Familial clustering (does not conform to patterns of Mendelian inheritance). Recurrence risks ~2–4% (compared to higher risks in Mendelian disorders) Caused by interaction of genetic and environmental factors None of these factors are well understood! Multifactorial Inheritance: Congenital malformations Cleft lip/palate Congenital dislocation of the hip Congenital heart defects Neural tube defects Pyloric stenosis Talipes Multifactorial Inheritance: Acquired diseases of childhood and adult life Asthma Autism Diabetes mellitus Epilepsy Glaucoma Hypertension Inflammatory bowel disease (Crohn disease/ulcerative colitis) Ischaemic heart disease Ischaemic stroke Manic depression Multiple sclerosis Parkinson disease Psoriasis Rheumatoid arthritis Schizophrenia Theory of Polygenic inheritance (Continuous inheritance) Many genes at different loci, with each gene exerting a small additive effect Effects of the genes are cumulative i.e. no one gene is dominant or recessive Applies to characteristics that show normal distribution in the population e.g. height, IQ (bell curve) ? Application of this model to discontinuous multifactorial disorders (affected/not affected) Liability / Threshold Model ‘Bad’ genes + adverse environmental factors = liability to disorder Liability = continuous variable (normal distribution) Above threshold abnormal phenotype expressed. General population – beyond the threshold is the population incidence Relatives of cases – beyond the threshold is the familial incidence Recurrence risk depends on number of affected relatives and closeness to index case