Multifactorial Disorders

Question 1

how do you study for multifactoral genetic diseases

Answer 1

twin studies or sibling relative risk

Question 2

what do you look for when studying genetic variants that contribute to multifactorial disease

Answer 2

SNP’s, haplotypes, genome wide association studies (GWAS)

Question 3

what are some examples of multifactorial diseases

Answer 3

Schizo
ALzh
Ageing muscular dystrophy
Diab 1

Question 4

what are the 4 types of multifactoral disorders

Answer 4

mendelian - obey menders law of segregation ie dominant, recessive, x linked

complex - inherited but non-mendelian

polygenic - multiple genes involved

multifactoral - both genetic and environmental factors

Question 5

how do twin studies aid in assess genetic factors in multifactoral diseases

Answer 5

genetic characteristics should have higher concordance in MZ (identical) compared to DZ (non-identical) but this high concordance doesn’t automatically prove a genetic effect

Question 6

how do family studies aid in assessing genetic factors in multifactoral diseases

Answer 6

population risk of a condition compared to the risk of an individual who’s sibling has that condition
if the risk is higher in siblings then points toward genetic component

Question 7

define heritability

Answer 7

proportion of multifactoral causation of a common disease that can be attributed to genetic factors

Question 8

what type of mulitfactoral disease is Schiz

Answer 8

inherited but not mendelian ie complex

Question 9

what is the COMT gene associated with

Answer 9

increased risk of SCIZo -

Question 10

what makes scizo multifactoral

Answer 10

first cousins then risk is doubled compared to general pop
half siblings more likely than aunt/uncle so suggest environ
COMT gene - genetic
cannabis use - environ

Question 11

what are phenotypes determined by

Answer 11

action of many genes at different loci

Question 12

what is additive

Answer 12

two or more genes source a phenotype

Question 13

what type of disorders show multifactoral inheritance

Answer 13

congenital malformations - cleft lip, heart defects, pyloric stenosis

acquired diseases - asthma, autism, cancer, diabetes, bipolar disorder, MS

effect of environment - genes combined with environment can modify risk

Question 14

what is alzh

Answer 14

most common form of dementia over 40
inability to cope, loss of memory, brain damage
shrinkage of bran, amyloid B protein in nerve fibres of hippocampus

Question 15

what is early onset alzh caused by

Answer 15

genetically heterogenous
PSEN1 and PSEN1 - responsible for proteolytic cleavage of amyloid B A4 precursor protein and NOTCH receptor proteins
missense in APP

Question 16

how does APOE affect Alzh

Answer 16

three types E2, E3, E4
E4 - confers increase in susceptibility
E 2 - confers protective effect

Question 17

what is linkage analysis

Answer 17

used to study family based linkage for allele low in frequency in a population but have a large effect on phenotype

Question 18

what is linkage disequilibrium

Answer 18

explains that two or more observed allele over time are commonly linked together

Question 19

linkage studies can be used to study what type of polymorphism

Answer 19

SNP’s

single nucleotide

Question 20

how do linkage studies look at SNP’s

Answer 20

linkage disequilibrium blocks and tag SNPs

Question 21

what is AMD, age related macular degeneration

Answer 21

leading cause of visual dysfunction (characterised by lipid deposits)
has both environmental and genetic risk factors
(chromsome 1 and 10, smoking)

Question 22

what is a manhattan plot

Answer 22

visualisation of GWAS results where all snp results are plotted
x axis shows position in the genome and y shows the significance

Question 23

define these terms: 
direct association
indirect 
spurious association type 1 error 
populations stratification 
systematic error

Answer 23

locus is a causal/functional variant

locus is in linkage disequilibrium with a causal variant

tested so many sips so need to repeat for reliability (chance finding due to so many tests)

turns out all the people all originated from one little village ten migrated

replication in independent cohorts across ethnic groups is necessary

Question 24

what are the limitations of GWAS

Answer 24

need large sample 
small effect size 
association not causation 
doesn't give underlying mechanism 
potential false positive 
focus on common genetic variation

Question 25

why don’t most inherited phenotypes follow mendelian rule

Answer 25

polygenic and complex which become emultifactoral