B&B Genetics

Question 1

inheritance that does not follow one of the mendelian patterns seen in single-gene disorders but complex diseases; arises from genetic factors and environmental factors
-empirically-derived risk figures are given to patients, because geneticists do not have an explanation for the underlying mechanisms of gene-gene and gene-environment interactions

Answer 1

multifactorial inheritance

Question 2

disease is present or absent

-discrete trait

Answer 2

qualitative trait

Question 3

measurable, physiological or biochemical quantities such as height, bp, cholesterol, BMI, factors underlie many of the devastating illnesses

Answer 3

quantitative trait

Question 4

affected individuals cluster in families

Answer 4

familial aggregation

Question 5

two related individuals in a family have the disease

Answer 5

concordance

Question 6

only one family member of a pair has the disorder/disease

Answer 6

discordance

Question 7

λr = (prevalence of disease in the relatives of an affected person)/(prevalence of disease in general population)

Answer 7

relative risk ratio

Question 8

indicates that a relative is NOT more likely than any other individual in the population to develop the disorder

Answer 8

relative risk ratio = 1

Question 9

disease concordance < 100% in MZ twins

Answer 9

strong evidence nongenetic factors play a role in disease

Question 10

greater concordance in MZ twins versus DZ twins

Answer 10

strong evidence the disease has a genetic component

Question 11

limitation of twin studies

Answer 11

1. MZ twins do not have identical gene expression, despite starting with identical copy
   (ex: random X inactivation, disparity of conditions within the womb, somatic rearrangements in immunoglobulin & T cell receptor loci)
2. MZ twins who volunteer for a study are more likely to be in concordance than those MZ twins asked to participate in a study

Question 12

the square of the standard deviation

Answer 12

variance

Question 13

the spread of values on either side of the mean

Answer 13

standard deviation

Question 14

the variance of a measured quantity in the population

Answer 14

total phenotypic variance

Question 15

quantifies the role of genetic differences in determining the variability of quantitative traits
-Reflects the measure of the extent to which different alleles at various loci are responsible for the variability in a given quantitative trait seen across a population
value = 0 means genes contribute nothing
value = 1 means the genes are totally responsible for phenotypic variance
= (variance in DZ pairs - variance in MZ pairs)/ variance in DZ pairs

Answer 15

heritability (h^2)

Question 16

relationship exists

range 0 to +1

Answer 16

positive correlation

Question 17

no similarity

range 0 to -1

Answer 17

negative correlation

Question 18

limitations of heritability

Answer 18

1. relatives share environment as well as genes
2. high heritability does not reveal the number of loci involved or how those loci interact
3. cannot be considered in isolation from the population group (ex: living conditions)

Question 19

Common errors in risk calculation

Answer 19

1. if children only share one parent, they are second-degree relatives, not first
2. when an uncle or aunt asks about the risk of the defect in their offspring, the relevant risk is specific to the offspring & they are third-degree relatives
3. be suspicious that diseases with unusual pattern are caused by a single gene with mendelian inheritance pattern, masked by small family size and incomplete penetrance

Question 20

• protein component of LDL particle involved in clearing LDL through interaction with high affinity receptors in the liver
• participates in lipid transport between tissues and cells
• function in brain is unknown
• constituent of amyloid plaques that binds AB-peptide in Alzheimer’s disease

Answer 20

ApoE

Question 21

mutations associated with early onset Alzheimer’s disease

Answer 21

1. APP
2. PSEN1
3. PSEN2
   Note: ApoE mutations not associated with monogenic AD but its presence increases risk

Question 22

cofactor for gamma secretase

Answer 22

PSEN1

Question 23

maintains neuronal integrity, influences microtubule assembly maintaining polarity and axonal transport

Answer 23

tau protein

Question 24

fully penetrant mutations in Alzheimer’s disease

Answer 24

APP
PSEN1
*PSEN1 is associated with early onset at age 45 with rapid progression

Question 25

not fully penetrant mutation in Alzheimer’s disease that is associated with slow progression

Answer 25

PSEN2