Week 1 - Complex Traits

Front 1

complex traits

Back 1

traits whose cause consists of two or more related genetic or environmental factors

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concordant

Back 2

both members of a twin pair share a trait

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discordant

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members of a twin pair do not share a trait

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empirical risk

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risk of occurrence or recurrence of a disease that is based on observation of data in many families with the disease, rather than simple Mendelian ratios; commonly used for genetic counseling for complex or multifactorial disorders

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Familial aggregation

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clustering of individuals with a disorder within families

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Heritability

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percentage of population variation in a trait that is due to genes as opposed to environmental influences

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Multifactorial

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disease or trait caused by the combined effect of multiple genetic and environmental factors

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Polygenic

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disease or trait caused by the combined effect of multiple genes

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Quantitative traits

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physical characteristics that are measured on a continuous numerical scale, such as height and blood pressure

Front 10

What is the difference between the Western and Eastern view of medicine? Why it important to consider the Eastern view?

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The Western view defines disease and health as opposites, and that a person is either one or the either. The Eastern view values balance, and describes disease and health on a spectrum. In this context, we must look at our patients more comprehensively and take into account both genes and environment

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Are any diseases controlled only by a single gene?

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This is debatable. Dr. Grody believes the answer is no, since almost even "single gene" diseases are affected by other genes and environmental factors

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Why is PKU, which is traditionally believed to be a recessive, single gene disease, said to also be controlled by other factors? Cystic fibrosis?

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In certain environmental conditions, the patient's phenotype is normal (altering the patient's diet). For cystic fibrosis, there are homozygous recessive (disease), who do not have the disease. This is because of other modifier genes which have an effect

Front 13

How are AIDS and trauma caused by genetic factors?

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AIDS - a polymorphism affects the HIV receptor in some individuals, making them more resistant
Trauma - risk taking behavior is genetically influenced

Front 14

What is lambda, the relative risk ratio (measuring familial aggregation of disease)

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This compares the prevalence of a disease in a certain family compared to the general population. A lamda of 1 indicates the family is at no greater risk than the general population, but higher than one indicates the family is at greater risk.

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What is heritability? How is it calculated?

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Heritability is a ratio that represents how much a disease or condition is caused by genes, as opposed to the environment. When h is high (near 1), the disease is caused mostly by genes. When is near 0, the disease is mostly environmental. It is often calculated by using the concordance of twins. One calcuation is 2 x (concordance of monozygotic twins - condordance of dizygotic twins).

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Measles has an h of .3 What does this mean? Autism has an h of about 1. What does this mean?

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In measles, H is near 0, meaning that this disease is due largely to environmental factors. Autism is near 1, indicating that it is mostly genetic.

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Say twenty genes are involved in an inherited disease. Patients with the disease have on average mutated forms of 5 of these genes. Are these the same 5 genes for all patients.

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No! Even WHICH genes out of the group can be variable. It is very complicated.

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How is Alzheimer's disease controlled by genes?

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In two ways. In one way (10% of patients), the disease is monogenic and highly penetrant. This form appears early, in about the third decade of life. In other forms, AD appears sporadically, but is more likely if the E4 form of the apoliprotein E is present. Environmental factors are at work too - patients with E4 and experienced head trauma are more likely to develop AD

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Is testing for E4 (APOE) recommended to test for Alheimer's in healthy patients?

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No. The predictive value is poor, and there is no effective intervention anyway.

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A company has sequenced the BRCA1 and BRCA2 gene in over 150,000 people. Has it discovered all of the variations? Why is this significant?

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It has not.. in fact it discovers 10-20 new missense mutations each week. This is significant because it reveals how incredibly complex the genetic variation is, and how it may be futile to try to find every single variation.