Exam 2 - Multifactorial disease Flashcards
Multifactorial disease
Multifactorial inheritance
Traits that are influenced by multiple genes (polygenic) and are also environmentally influenced
Mendelian genetics
Describes a trait that is attributable to a single gene
Threshold model
Persons on low end of distribution have a low chance of developing disease (few alleles or environmental factors that would cause disease)
Persons closer to high end have a greater chance of developing disease (greater disease causing alleles and envt factors)
For multifactorial diseases that are either present or absent a __________ must be crossed before diseases is expressed
Threshold of liability
Empirical risk
used to understand recurrence in multifactorial inheritance
Empirical recurrence risks for multifact. disease are based off of:
Studies of large collections of families
It is difficult to differentiate from ______ from single gene disease that have _______
multifactorial disease
reduced penetrance/variable expression
Recurrence risks are ______ if more than one family member is affected
higher
If disease expression in proband is ________, recurrence risk is _______
more severe
higher
Recurrence risks are ______ if proband is of _________
higher
less commonly affected sex
Recurrence risks usually ________ in more remotely related relatives
decrease rapidly
If prevalence of disease in a pop is f:
risk for offspring and siblings of proband is √f
Multi factorial disease:
Dermatoglyphics Neural tube defects: Spina bifida DM MI HTN MS Atherosclerosis Alzheimers Alcoholism
Concordance values
If both twins share a trait, it is concordant
If they don’t share trait they are discordant
For a trait determined completely by genes:
MZ twins should be concordant and DZ concordant less often
Heritability
the percentage of population variation in a trait that is due to genes
Heritability equation
h = 2(CMZ – CDZ)
Different Approaches used to Identify Genes Underlying Multifactorial Traits:
Quantitative trait loci (QTL’s)
QTL examples:
- Conventional Linkage Analysis
- Affected sib-pair method
- animal models and genome scanning
- Genome wide association studies (GWAS)
Genome wide association studies (GWAS)
- looks at SNPs in diseased pop and control pop to determine degree of association with disease
GWAS big debate:
look for the few rare genes more likely found in extreme phenotypes vs. looking for more common genes associated with phenotype that are greater in number but each having a smaller effect
Animal model:
nml phenotype X extreme phenptye
Result: Heterozyg. off spring…. X with nml offspring
Off srping wiht recombinations used to map QTL’s
8 factors influencing hypertension:
salt obesity smoking inactivity alcohol genetics stress low K, Mg and Ca
