Multifactorial Disorders Flashcards
how do you study for multifactoral genetic diseases
twin studies or sibling relative risk
what do you look for when studying genetic variants that contribute to multifactorial disease
SNP’s, haplotypes, genome wide association studies (GWAS)
what are some examples of multifactorial diseases
Schizo
ALzh
Ageing muscular dystrophy
Diab 1
what are the 4 types of multifactoral disorders
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
how do twin studies aid in assess genetic factors in multifactoral diseases
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
how do family studies aid in assessing genetic factors in multifactoral diseases
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
define heritability
proportion of multifactoral causation of a common disease that can be attributed to genetic factors
what type of mulitfactoral disease is Schiz
inherited but not mendelian ie complex
what is the COMT gene associated with
increased risk of SCIZo -
what makes scizo multifactoral
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
what are phenotypes determined by
action of many genes at different loci
what is additive
two or more genes source a phenotype
what type of disorders show multifactoral inheritance
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
what is alzh
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
what is early onset alzh caused by
genetically heterogenous
PSEN1 and PSEN1 - responsible for proteolytic cleavage of amyloid B A4 precursor protein and NOTCH receptor proteins
missense in APP
how does APOE affect Alzh
three types E2, E3, E4
E4 - confers increase in susceptibility
E 2 - confers protective effect
what is linkage analysis
used to study family based linkage for allele low in frequency in a population but have a large effect on phenotype
what is linkage disequilibrium
explains that two or more observed allele over time are commonly linked together
linkage studies can be used to study what type of polymorphism
SNP’s
single nucleotide
how do linkage studies look at SNP’s
linkage disequilibrium blocks and tag SNPs
what is AMD, age related macular degeneration
leading cause of visual dysfunction (characterised by lipid deposits)
has both environmental and genetic risk factors
(chromsome 1 and 10, smoking)
what is a manhattan plot
visualisation of GWAS results where all snp results are plotted
x axis shows position in the genome and y shows the significance
define these terms: direct association indirect spurious association type 1 error populations stratification systematic error
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
what are the limitations of GWAS
need large sample small effect size association not causation doesn't give underlying mechanism potential false positive focus on common genetic variation
why don’t most inherited phenotypes follow mendelian rule
polygenic and complex which become emultifactoral
