Human Molecular Genetics Flashcards
What are environmental factors to development/disease?
Physical
Chemical
Biological
What are genetic factors to development/disease?
Polygenic
Monogenic
What did Richard Doll prove?
That smoking caused lung cancer
How are over 4,000 human diseases caused by?
Single gene defects§
What studies are helpful when determine environmental genetics effects on diseases/developments?
Twin studies
What can defective enzymes have a major consequence for?
Metabolic pathways
Where can mutation occur to cause loss of function or gain of function?
Protein-coding genes
Define dominant referring to modes of inheritance:
Vertical patterns of affected individuals
Define recessive referring to modes of inheritance:
Horizontal patterns of affected individuals
Define autosomal recessive referring to modes of inheritance:
Consanguinity often present between parents
Define autosomal referring to modes of inheritance:
Males and females affected with equal probability
Define X-linked recessive referring to modes of inheritance:
Males affected, female carriers
Define X-linked dominant referring to modes of inheritance:
All daughters of affected males are affected
Define mitochondrial referring to modes of inheritance:
Non-Mendelian
Maternal inheritance
What is consanguinity?
The property of being from the same kinship as another person
How can you tell if the disease is autosomal dominant in a pedigree?
- Affects each generation
- Both sexes
- Normal siblings of affected individuals do not transmit the trait to their offspring.
Example of autosomal dominant diseases:
- Huntington’s disease (Huntington’s chorea)
- Polycystic kidney disease
- Familial hypercholesterolaemia
How can you tell if the disease is autosomal recessive in a pedigree?
- Males and females are equally likely to be affected
- Found in siblings, not parents of affect or the offsprings of affected
- Consanguineous mating
Examples of autosomal recessive:
- Cystic fibrosis
- Phenylketonuria
- Sickle cell anaemia
How can you tell if the disease is x-linked recessive in a pedigree?
- Never passed from father to son
- Males more affected than females
- Passed from an affected grandfather, though his carrier daughters then to half of his grandsons
Examples of x-linked recessive:
- Duchenne muscular dystrophy
- Haemophilia A and B
How can you tell if the disease is non-mendelian (mitochondrial) in a pedigree?
Everyone inherits the condition from the maternal line
Examples of mitochondrial disease:
- Leber’s hereditary optic neuropathy (LHON)
- Myotonic epilepsy and ragged red muscle fibre disease (MERRF)
What 6 complications can affect the interpretation of pedigrees?
- New mutations
- Penetrance
- Expressivity
- Delayed onset
- Anticipation
- Imprinting
What is complete penetrance?
The allele is said to have complete penetrance if all individuals who have the disease-causing mutation have clinical symptoms of the disease
What is highly penetrant?
If an allele is highly penetrant, then the trait it produces will almost always be apparent in an individual carrying the allele
What is incomplete penetrance or reduce penetrance?
Penetrance is said to be reduced or incomplete when some individuals fail to express the trait, even though they carry the allele.
What is low penetrance?
An allele with low penetrance will only sometimes produce the symptom or trait with which it has been associated at a detectable level. In cases of low penetrance, it is difficult to distinguish environmental from genetic factors
How to identify a disease gene?
-Chromosomal location
-Gene
-mRNA/cDNA
-Protein
(POSITIONAL CLONING CAN TAKE PLACE BETWEEN ANY STAGE)
What is positional cloning?
Laboratory technique used to locate the position of a disease-associated gene along the chromosome
What is cytogenetics?
Diseases correlate with a visible chromosomal deletion or rearrangement
What doe genetic linkage allow in terms of disease?
Disease genes to be mapped
What can be used when mapping?
Molecular markers
What are different types of markers?
- Phenotypic markers
- Molecular markers
Examples of molecular markers:
- Structural rearrangements
- SNPs
- RFLPs
- INDELS
- Copy number variations eg VNTRs with multiple alleles
How can be used for genetic linkage analysis?
Log Odds Scores
What is the equation for lod score?
Log10 (odds loci linked/odds loci are unlinked)
What are Lod scores?
- Logarithms
- Data from separate families can be polled from different pedigrees by adding lod scores
What does a lod score greater than or equal to 3.0 indicate?
Likelihood of observing the given pedigrees if the two loci are not linked is less than 1 in 1000
Why has there been so much progress in identifying common disease genes?
- Genome wide association studies (GWAS) mean we can study a large proportion of the common human variation in one experiment
- GWAS employ case-control design comparing two large groups of individuals
- All individuals in each group are genotyped for the majority of common known SNPs.
- Association is then measures using Log scores
What diseases did GWAS reveal be associated with five major polymorphism?
Age-related macular degeneration
Is it genetics or environment when the gene pool has changed very little over the same period?
Environment
