Human Molecular Genetics Flashcards
Which scientist linked a wide range of cancers to chemicals found in our environment?
Sir Richard Doll.
Give the definition of a monogenic disease.
Usually rare and caused by loss or gain of function mutations in protein-coding genes. Can be dominant, recessive or X-linked.
How do we know if common traits have a genetic component?
- twin, family and admixture studies have suggested that type 2 diabetes has a genetic component.
- in twins, monozygotic twins are 40% more likely to have type 2 diabetes if the other twin has it.
- in families, risk of type 2 diabetes in sibling of affected person is 3-4x greater than the general population risk.
- population, European admixture lowers diabetes risk in Nauruans (17% vs 83%)
Give all the modes of inheritance.
Dominant Recessive Autosomal recessive Autosomal X-linked recessive X-linked dominant Mitchondrial
Patterns found in dominant inheritance.
Vertical patterns of affected individuals.
Patterns found in recessive inheritance.
Horizontal patterns of affected individuals.
Patterns found in autosomal recessive inheritance.
Consanguinity often present between parents.
Patterns found in autosomal inheritance.
Males & females affected with equal probability.
Patterns found in X-linked recessive inheritance.
Males affected, female carries.
Patterns found in X-linked dominant inheritance.
All daughters of affected males are affected.
Patterns found in mitochondrial inheritance.
Non-Mendelian, maternal inheritance.
Give the complications that effect interpretation of pedigrees.
- new mutations
- penetrance
- expressivity
- delayed onset
- anticipation
- imprinting
Describe how to identify a disease gene.
- simple protein involved > mRNA/cDNA > gene
- map to chromosomal locus (positional cloning)
Describe how genetic linkage allows disease genes to be mapped.
- measured from recombination frequencies between 2 markers in crosses
- humans are not ideal for this
- molecular or phenotypic markers allow mapping
- molecular markers eg structural rearrangements, SNPs, RFLPs, INDELS, copy no. variations eg VNTRs with multiple alleles
Describe genetics linkage analysis, Logs Odd Scores.
- use stats analysis
- lod score = log10 (odds loci are linked/ odds loci are unlinked)
- lod scores are logarithms so data from different families can be pooled from different pedigrees by adding log scores
- lod score > 3.0 indicates likelihood of observing the given pedigrees if the 2 loci are not linked is less than 1 in 1000. (ie they are because without linkage seeing the same pattern in both would be very unlikely)
Why has GWAS facilitated large progress in identifying common diseases?
We can study a large proportion of the common human variation in one experiment.
Why can increased incidence of obesity (and diabetes) not be 100% due to changing genes or environment?
- we can say that the obesity epidemic is 100% environmental and 0% genetic
- EXCEPT twin studies have shown that there is a genetic component, while BMI has increased as a result of changing environments, where you sit in that distribution is determined by >50% of your genetics.
Give the definition of quantitative traits.
Traits that vary continuously