Multifactorial Inheritance Flashcards
What are multifactorial conditions?
Diseases that are due to a combination of genetic and environmental factors
Most common diseases are multifactorial
How do you identify that a condition has a genetic component?
By clinical observation
•Family studies
•Twin studies
•Adoption studies
Explain Traditional Clinical Genetic Techniques – Twin Studies
Compare genetically identical (MZ) with genetically non-identical (DZ) twins
•The concordance rate is the % of twin pairs studied that both have the condition. If a condition has a genetic component you would expect the concordance rate to be higher in monozygotic twins than in dizygotic twins. The concordance rates give a rough figure for the hereditability of a multifactorial disorder
•The high risk for MZ twins is found even when they are reared apart
Explain Traditional Clinical Genetic Techniques – Adoption studies
adopted children of a parent with a multifactorial condition have a high risk of developing the disease
•compare above with a group of adoptees with normal biological parents and an adoptive parent with the condition – they have a low risk
•Can look at adopted individuals with a condition and look at the rates of that condition in the biological and adoptive families – high in the biological families only
Explain Hereditability
The proportion of the aetiology that can be ascribed to genetic factors as opposed to environmental factors
•expressed as a proportion of 1 or as a percentage e.g.in schizophrenia hereditability is about 0.85 or 85%
•one way to calculate the hereditability is from the concordance rate in monozygotic twins
What are characteristics of Multifactorial Inheritance?
The incidence of the condition is greatest amongst relatives of the most severely affected patients
•The risk is greatest for the first degree relatives and decreases rapidly in more distant relatives
•If there is more than one affected close relative then the risks for other relatives are increased
If the condition is more common in one particular sex, then relatives of an affected individual of the less frequently affected sex will be at higher risk than relatives of an affected individual of the more frequently affected sex.
What is liability?
The factors that influence the development of a multifactorial disorder, genetic and environmental can be considered as a single entity
Once you have established that a condition has a genetic component to it how do you work out what that genetic component is?
Use GWAMS - Genome wide association studies
What is GWAS?
•Utilises the fact that a gene can have several variants –alleles
•Some variations in a gene cause that gene to be inactivated or behave abnormally – pathogenic
•Most genetic variation still results in a functioning gene – polymorphisms
•Different types of polymorphisms – e.g. SNPs (single nucleotide polymorphisms), differing lengths of a CA repeat.
What does GWAS do?
Compares the frequency of markers in a sample of patients and a sample of healthy controls. Can use candidate genes or nowadays try to aim for complete coverage of the genome
What a neural tube defects?
Defective closure of the developing neural tube during the first month of embryonic life
If multifactorial disease is due to the interaction of genes with environmental factors what are the environmental factors? (Embryogenesis)
Drugs and Chemicals e.g. thalidomide, anticonvulsants, alcohol
•Maternal Infections e.g. rubella, CMV
•Physical Agents e.g. radiation
•Maternal Illness e.g. diabetes, phenylketonuria
If multifactorial disease is due to the interaction of genes with environmental factors what are the environmental factors? (Post natal)
•Type 2 diabetes
–Obesity
•Breast cancer
–Hormonal factors
•The pill, HRT, parity, breast feeding, obesity
•Lung cancer
–Smoking
•Schizophrenia
–Recreational drugs
