Transcript Introduction to Inheritance - Goring & Woodcote Medical Practice

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
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Non carrier
girl
Non carrier
boy
Carrier
girl
Affected
boy
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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
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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)
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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)
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? Application of this model to discontinuous
multifactorial disorders (affected/not affected)
Liability / Threshold Model
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‘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