19. Polygenic inheritance and disease Flashcards
what is the normal distribution in the general population caused by
the interaction of several genes, known as polygenes, each of which makes a small contribution to the overall phenotype
polygenetic disorders
These are caused by the combined effects of multiple genes, along with environmental factors.
quantitative genetics
the study of genetically determined continuous traits
enviromental effects and polygenic inheritance
they play a part in determining whether or not a particular set of variants of polygenes produces a clinical disorder
regression to the mean
the tendency of offspring for any continuous polygenic trait to be closer to the population mean than their mid-parental value
examples of the many common congenital inheritance
- cleft lip and palate
- neural tube defects
- congenital heart disease
common disorders of adult life which have evidence of environmental effects
- coronary heart disease
- diabetes mellitus
- schizophrenia
liability threshold model
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
what is different about a liability curve (for eg. cleft lip) for the relative of someone
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)
multifactorial inheritance
combination of environmental and genetic factors give rise to the condition
Hirschsprung’s disease
absent autonomic innervation of colon
(nerves responsible for controlling the function of the colon are not present of functioning properly)
for a mild condition of Hirschsprung’s where is affected
the short segment of the colon
for a severe condition of Hirschsprung’s where is affected
long segment of the colon
recurrence risk for a sibling of affected boy (Hirschsprung’s disease)
short segment - 2%
long segment - 13%
recurrence risk for a sibling of affected girl (Hirschsprung’s disease)
long segment - 18%
long segment - other affected relatives - 30%
Heritability
how much of a disorder is caused by genes
how can heritability be calculated
the recurrence risk of a disorder in first degree relatives compared to the population incidence
heritability of coeliac
15:1
other approaches to identify heritability
family studies
twin studies
adoption studies
population/migration studies
explain family studies as an approach to identify heritability
- 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.
twin studies as an approach to identify heritability
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
explain how adoption studies is used as an approach to identify heritability
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.
explain how migration studies is used as an approach to identify heritability
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
methods for identifying susceptibility genes
1) linkage analysis
2) sib-pair analysis
3) disease associations
4) animal models
5) candidate genes
diabetes mellitus
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
concordance
both twins have the same condition
twin studies for diabetes mellitus
MZ twins - 45-96% concordance
DZ twins - 3-37% concordance
risk of NIDDM (diabetes- rare mitochondrially inherited)
population risk; 4-5%
1st degree relatives: 10-15% risk
risk of IDDM (type 1)
population risk: 0.2%
risk for siblings: 7%
risk for offspring: 4%
coronary artery disease
Thickening of blood and build up of plaque blocking blood vessels, reducing blood flow to the heart
epidemiology
patterns and factors that determine health related conditions
familial hypercholesteralaemia
autosomal dominant disorder - mutations in LDL receptor gene
Schizophrenia
serious psychiatric disorder with an onset in late adolescnece/early adult life
what are the symptoms of Schizophrenia
- disorganized thought and behaviour
- deterioration in social and occupational functioning
- can be accompanied by hallucinations and/or delusions
what is the lifetime risk of Schizophrenia
1%
when is there an increased risk of Schizophrenia
increased risk with poorer socio-economic status
what is the chromosome disorder linked to Schizophrenia
22q11 deletion syndrome - Di George syndrome
