19. Polygenic inheritance and disease

Question 1

what is the normal distribution in the general population caused by

Answer 1

the interaction of several genes, known as polygenes, each of which makes a small contribution to the overall phenotype

Question 2

polygenetic disorders

Answer 2

These are caused by the combined effects of multiple genes, along with environmental factors.

Question 3

quantitative genetics

Answer 3

the study of genetically determined continuous traits

Question 4

enviromental effects and polygenic inheritance

Answer 4

they play a part in determining whether or not a particular set of variants of polygenes produces a clinical disorder

Question 5

regression to the mean

Answer 5

the tendency of offspring for any continuous polygenic trait to be closer to the population mean than their mid-parental value

Question 6

examples of the many common congenital inheritance

Answer 6

• cleft lip and palate
• neural tube defects
• congenital heart disease

Question 7

common disorders of adult life which have evidence of environmental effects

Answer 7

• coronary heart disease
• diabetes mellitus
• schizophrenia

Question 8

liability threshold model

Answer 8

Concept that is used to explain how certain common disorders, which do not follow traditional Mendelian inheritance patterns can still cluster within families. In this model it is proposed that the risk of developing a disorder is determined by a combination of genetic and environmental factors

Question 9

what is different about a liability curve (for eg. cleft lip) for the relative of someone

Answer 9

the relative of someone with cleft lip is more likely to have cleft lip and therefore the threshold is lower (curve shifted more to the right)

Question 10

multifactorial inheritance

Answer 10

combination of environmental and genetic factors give rise to the condition

Question 11

Hirschsprung’s disease

Answer 11

absent autonomic innervation of colon
(nerves responsible for controlling the function of the colon are not present of functioning properly)

Question 12

for a mild condition of Hirschsprung’s where is affected

Answer 12

the short segment of the colon

Question 13

for a severe condition of Hirschsprung’s where is affected

Answer 13

long segment of the colon

Question 14

recurrence risk for a sibling of affected boy (Hirschsprung’s disease)

Answer 14

short segment - 2%
long segment - 13%

Question 15

recurrence risk for a sibling of affected girl (Hirschsprung’s disease)

Answer 15

long segment - 18%
long segment - other affected relatives - 30%

Question 16

Heritability

Answer 16

how much of a disorder is caused by genes

Question 17

how can heritability be calculated

Answer 17

the recurrence risk of a disorder in first degree relatives compared to the population incidence

Question 18

heritability of coeliac

Answer 18

15:1

Question 19

other approaches to identify heritability

Answer 19

family studies
twin studies
adoption studies
population/migration studies

Question 20

explain family studies as an approach to identify heritability

Answer 20

• Families that are known to have individuals affected by the trait or disorder of interest are selected.
• Pedigree charts are used to map out the family tree and document the presence or absence of the disorder amongst family members.
• By comparing the prevalence of the trait or disorder among relatives, researchers can estimate the heritability of the trait.

Question 21

twin studies as an approach to identify heritability

Answer 21

Identical twins will have the same genetic makeup. If there is a condition that has a genetic component to it you will expect to see it far more often in identical twins compared to non identical twins

Question 22

explain how adoption studies is used as an approach to identify heritability

Answer 22

comparing adopted individuals with their biological relatives and their adoptive relatives This allows researchers to examine the influence of genetic and environmental factors on the trait or disorder of interest.

Question 23

explain how migration studies is used as an approach to identify heritability

Answer 23

Migration studies focus on populations that have migrated from one geographic region to another. By comparing the prevalence of the trait or disorder in migrants with their native and host populations, researchers can examine how changes in environment or genetic background affect the trait

Question 24

methods for identifying susceptibility genes

Answer 24

1) linkage analysis
2) sib-pair analysis
3) disease associations
4) animal models
5) candidate genes

Question 25

diabetes mellitus

Answer 25

a disease with both genetic and environmental components

• type 1: insulin dependent and childhood onset
• type 2: non-insulin dependent and onset usually after 50 years

Question 26

concordance

Answer 26

both twins have the same condition

Question 27

twin studies for diabetes mellitus

Answer 27

MZ twins - 45-96% concordance
DZ twins - 3-37% concordance

Question 28

risk of NIDDM (diabetes- rare mitochondrially inherited)

Answer 28

population risk; 4-5%

1st degree relatives: 10-15% risk

Question 29

risk of IDDM (type 1)

Answer 29

population risk: 0.2%

risk for siblings: 7%

risk for offspring: 4%

Question 30

coronary artery disease

Answer 30

Thickening of blood and build up of plaque blocking blood vessels, reducing blood flow to the heart

Question 31

epidemiology

Answer 31

patterns and factors that determine health related conditions

Question 32

familial hypercholesteralaemia

Answer 32

autosomal dominant disorder - mutations in LDL receptor gene

Question 33

Schizophrenia

Answer 33

serious psychiatric disorder with an onset in late adolescnece/early adult life

Question 34

what are the symptoms of Schizophrenia

Answer 34

• disorganized thought and behaviour
• deterioration in social and occupational functioning
• can be accompanied by hallucinations and/or delusions

Question 35

what is the lifetime risk of Schizophrenia

Answer 35

1%

Question 36

when is there an increased risk of Schizophrenia

Answer 36

increased risk with poorer socio-economic status

Question 37

what is the chromosome disorder linked to Schizophrenia

Answer 37

22q11 deletion syndrome - Di George syndrome