multifactorial inheritance Flashcards
define multifactorial diseases
diseases that are due to a combination of genetic and environmental factors
most common diseases are multifactorial
how do you identify that a condition has a genetic component
by clinical observation
- family studies - inheritance patterns
- twin studies
- adoption studies
how do you use family studies in genetic research
compare the incidence of a disease amongst the relatives of an affected individual with the general population
what are 4 characteristics of the risk of a multifactorial condition
- the risk of the condition in relatives of an affected individual is dramatically higher than in the general population
- the risk varies directly with the degree of genetic relationship, it is greatest for first-degree relatives and decreases rapidly in more distant relatives
- the risk varies with the severity of the patients illness, it is greatest amongst relatives of the most severely affected patients
- the risk varies with the number of relatives affected, if there is more than one affected close relative then the risk for other relatives is increased
how do you use twin studies in genetic research
compare genetically identical (MZ) with genetically non-identical (DZ) twins
the concordance rate is the % of twin pairs studied that both have the condition
if the condition has a genetic component then you would expect the concordance rate to be higher in MZ twins
the concordance rates give a rough figure for the hereditability of a multifactorial disorder
how do you use adoption studies in genetic research
adopted children of a parent with a multifactorial condition have a high risk of developing the disease
compare above with a group of adoptees with normal biological parents and an adoptive parent with the condition - they have a low risk
define hereditability
the proportion of causes that can be ascribed to genetic factors rather than environmental factors
how is hereditability expressed
as a proportion of 1 or as a percentage
what is a way to calculate hereditability
from the concordance rate in monozygotic twins
how does multifactorial inheritance act with sex
if the condition is more common in one sex, then relatives of an affected individual of the less frequently affected sex will be higher risk than relatives of an affected individual of the more frequently affected sex
define liability
the factors that influence the development of a multifactorial disorder, genetic and environmental can be considered as a single entity known as a liability
what does the liability / threshold model show
the liabilities of all individuals form a continuous variable which has a normal distribution
the curve for relatives is shifted to the right compared to the general population
the closer the relationship the greater the shift to the right
a threshold exists above which the abnormal phenotype is expressed
in the general population the proportion beyond the threshold is the population incidence and among relatives is the familial incidence
what is GWAS
Genome-Wide Association Studies
a research approach used to identify genomic variants that are statistically associated with a risk for a disease or a particular trait.
how does GWAS work
it utilises the fact that a gene can have several variants - alleles
some variations in a gene cause that gene to be inactivated or behave abnormally - pathogenic
most genetic variation still results in a functioning gene - polymorphisms
compare the frequency of markers in a sample of patients and a sample of healthy controls. can use candidate genes or nowadays try to aim for complete coverage of he gene
look for markers eg SNP that is seen more frequently in the disease population
sequence that area to try to identify the gene and the particular allele that is associated with the increased likelihood of developing the condition
what are neural tube defects
when the neural tube does not close properly during the first month of embryonic life
