population genetics- basics Flashcards
it is clear that some diseases have a major
environmental component
Sir William Richard Doll
british physiologist who was a pioneer in research linking smoke to health problem. He was credited for proving that smoking increased chances of lung cancer rand hear disease
proof in pictures of disease and enviroment
twins - twin on the right smoked and sunbathed her whole life
environmental factors
physical chemical biological
genetic
monogenic polygenic
how manny human diseases are caused by single gene defects
4000
defective enzymes can have a major consequence for
metabolic pathways
dominant
vertical pattern of individuals
recessive
horizontal patterns of affected individuals
autosomal recessive
consanguinity (incest) often between parents
autosomal
males and females affected with equal probability
X-linked recessive
ales affected, female carriers
X linked dominant
all daughter and males are affected
mitochondrial
non-mendelian- maternal inheritance
Dominant diseases
achondroplasia hungtintons
achondroplasia
dwarfism- a bone growth disorder
Huntington’s disease
neurofegenerive genetic disorder that affects muscle coordination and leads to cognitive decline and psychiatric probles
recessive
sickle cell anaemia CF
sickle cell anaemia
blood disorder effecting shape of the red blood cells and therefore their carry of oxygen capacity
Cystic fibrosis
autosomal recessive disorder caused by a mutation on a cl- channel- causes thick secretion of mucous and effects the lungs and various other organs
X-linked
duchene muscular dystrophy haemophilia
duchess muscular dystrophy
muscle degeneration which leads to death
hemophilia
when you can’t stop bleeding
hemophilia
when you can’t stop bleeding
common traits have a
genetic component e.g. twin, family and admixture studies indicate that type 2 diabetes and obesity have genetic components
monozygotic twins
40% will have type 2 diabetes if one does
dizygotic twins
around 10% will have type 2 if one does
Linkage
generally measured from recombination frequency between two markers in crosses- but humans are not ideal organisms for genetic since scientists can’t control who they breed with
why are humans not ideal organisms for genetics
can’t control who they breed with
markers can be used to
show up genetic disorders
markers used to show up genetic disorders
structural rearrangements SNPs RFLPs INDELs
SNPs
single nucleotide polymorphism
RFLPs
Restriction Fragment Length Polymorphism (RFLP) is a difference in homologous DNA sequences that can be detected by the presence of fragments of different lengths after digestion of the DNA samples in question with specific restriction endonucleases.
linkage and statistical analysis
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why has there been huge process in identifying common diseased genes
because genome wide association studies mean we can study a large proportion of the common human variation in one experiment. -GWA studies empty case-control design comparing two large groups (one being affected and the other as a control) -all individuals in each group are genotyped for the majority of common known SNP –> typically around a million Association is then measured using Lod score
Lod score
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pedigree symbols
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autosomal dominant -huntington’s -polycystic kidney disease Pedigree
-every affected individual has an affected biological parent -males and females equally likely to be affected -50% chance of recurrence -normally siblings to not transmit to offspring
autosomal recessive -CF Pedigree
-males and females are equally affected -recurrence risk of each child- 25% -traits characteristically found in siblings and not parents mating parents may be consanguineous (incest) traits may appear as an isolated event
consanguineous
incest
x-linked recessive -duchenne -haemophlia Pedigree
-males are much more likely to be affected -trat is never passed from rathe rot son -all affected males in a family are related through their mothers -passed from affected grandfather to carrier daughter
mitochondrial -leber hereditary optic neuropathy
Pedigree
-non-mendelian -everyone inherits the condition through the maternal line
complications that affect interpretation of pedigrees
- new mutations
- penetrance- low penetrance- sufferers would only sometimes produce the symptoms
- expressivity- patient always expresses some the symptoms of the disease and varies from very mildly affected to very severely affected
- delayed onset- some diseases do not express themselves until later in life, well beyond reproductive age
- anticipating 6.imprinting
pentrance
e.g. low penetrance- sufferers would onto sometimes produce some symptoms
expressivity
patients always express some symptoms of the disease and varies from very mildly affected to very severely affected
delayed onset
- some disease do not express themselves until later life, well beyond reproductive age.
how can diseased genes sometimes be identified
sometimes diseases will correlate with a visible chromosomal deletion or rearrangement e.g. translocation or duplication or delegation e.g. may be able to be seen on karyotypes
example pedigree of autosomal dominant with incomplete penetrance
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