Human Molecular Genetics Flashcards
Diseases caused by genetic components
Thousands of diseases and disorders mainly caused by genetic components
single mutations can lead to dramatic and severe changes in the phenotype
How do we know this?
twin studies
family and admixture studies indicate T2 diabetes has genetic component
strong evidence for inheritance- T2 not just reliant on environment
Define: Dominant mode of inheritance
vertical patterns of affected individuals
Define: recessive mode of inheritance
horizontal patterns of affected individuals
Define: autosomal recessive mode of inheritance
consanguinity often present between parents
Define: autosomal mode of inheritance
males and females affected with equal probability
Define: X-linked recessive mode of inheritance
males affected, females carriers
Define: X-linked dominant mode of inheritance
all daughters of males affected
Define: mitochondrial mode of inheritance
non-mendillian, maternal inheritance
What is consanguinity?
blood relation
property of being from the same kinship as the other person
How do you recognise autosomal dominant pedigree analysis?
easiest
every affected individual has an affected biological parent
no skipping of generations
males and females equally likely
How do you recognise autosomal recessive pedigree analysis?
males and females equally likely
reccurance risk of unborn sibling = 1/4
trait found in siblings
parents of affected may be related
trait may appear isolated (sporadic event)
How do you recognise X-linked recessive pedigree analysis?
disease never passed from father to son
males more likely
all affected males are related through their mothers
typically passed from affected grandfather, through carrier daughters, to half grandsons
may be lethal in males
How do you recognise mitochondrial pedigree analysis?
everyone inherits through the maternal line
What are the complications that affect interpretation of pedigrees?
- New mutations
- Penetrance
- Expressivity
- Delayed onset
- Anticipation
- Imprinting
How do you identify a diseased gene?
work backwards for root of disorder
What is positional cloning?
disease will correlate with a visible chromosomal deletion or rearrangement
spreading out the karyotype and relating to those who suffer genetic disorders
What markers can be used to help map diseased genes?
phenotypic markers
- genetic disorder
molecular markers
- structural arrangements
- copy number variations
- INDELs
What is the statistical analysis for linkage analysis?
log odds scores
lod score = odds loci linked / odd loci unlinked
> = 3 indicates not linked
- establish pedigrees
- number of estimates of recombination frequency
- calculate lod score of each estimate
What are GWAs?
Genome wide association studies
study large proportion of common human variation in one experiment
genotypes for common SNPs
What are some examples of GWAs?
Age related macular degeneration
Height
Obesity
What are the gene variations in obesity?
identified risk allele for obesity
carriers of gene weighed 1.2kg heavier than those without
carriers of 2 copies weight 3kg heaver
obesity major risk factor for developing diabetes
Is the obesity epidemic environmental or genetic?
100% environmental
gene pool change very little over the same period
twin studies show body mass has genetic component
so where people lie is >50% genetics
