Genetics:Pedigrees and Risk Flashcards
What are the main points for using a genetic pedigree?
Provides a clear simple summary of information
Able to spot patterns easily
Explain pattern to patient
Calculate the risk of passing on disease or being a carrier
Allows informed choice
How are generations denoted on genetic pedigree?
Using roman numerals
How are offspring birth ordered traditionally on genetic pedigrees?
Left tor right, individuals denote by Arabic numerals.
Conventionally, which side is paternal lineage and maternal lineage denoted on a genetic pedigree?
Paternal - right
Maternal - left
In relation to the proband which % of DNA is shared between grandparents?
25%
In relation to the proband, which % of DNA is shared between parents?
50%
In relation to the proband, which % of DNA is shared between siblings?
50%
In relation to the proband, which % of DNA is shared between Aunts & uncles?
25%
In relation to the proband, which % of DNA is shared between 1st degree cousins?
12.5%
What is classified as consanguineous mating?
Mating occurs if 2nd cousins or closer (3.13% shared DNA)
What pattern is provided by autosomal dominant conditions on a genetic pedigree?
Vertical transmission
The tendency for not all offspring expressing the conditions
Both genders are affected
Minimum of one parent required.
Why are some familial disorders not expressed within the pedigree?
Have an age of onset, developing with age due to an accumulation of sporadic mutations
Deceased patients may not develop the disease, thus not expressed within the pedigree
Which trinucleotide repeat causes Huntington’s?
CAG
What inheritance pattern is demonstrated by Huntington’s?
Monogenic autosomal dominant disorder
Unstable mutation confers for a variable number of repeats
How many CAG repeats cause full penetrance?
40+
How is mitochondrial inheritance conferred?
The mutated gene is present in the mitochondrial DNA of the ovum; subsequent.y mtDNA is exclusively inherited from maternal lineages
Which lineage has a strong inheritance pattern of mitochondrial DNA?
Maternal lineage
What type of transmission pattern is evident for mitochondrial DNA inheritance?
Vertical transmission
Affects all generations,both genders are affected since the mutated gene is inherited from the mother
What are the complicating factors of mitochondrial inheritance in terms of genomes and mt number?
Have multiple copies of genome ,therefore a proportion express normal genotype and mutant genotype
Offspring inherit varying numbers of mutated mitochondria this can change with time
What is the pattern of inherited mitochondrial disease and age? Explain
Diseases develop with age due to accumulation of mutated mitochondria
How do mitochondria replicate?
Binary fission
What is the definition of genetic risk?
Risk is the calculation of the predicted chance of having the disease or being a carrier
Risk can only be calculated based upon the known phenotype to subject
Multiplication of risks to calculate overall risk of inheriting genetic disorder
What are risk modifiers in terms of phenotypic advantage?
The lineages of the disease prevalence (maternal or paternal); X-linked and mitochondrial inheritance patterns
Ethnic background: Diseases have different prevalence in different populations
Example: CF, Sickle cell, Tay-Sachs
Whereby the heterozygous express a phenotypic advantage within the environment, the allelic frequency would increase within areas of relatively higher selection pressure
Founder effect
What is the founder effect?
Due to a genetic bottleneck, also produced sub-populations with increased prevalence
Which inheritance pattern is demonstrated by hereditary hemochromatosis?
Autosomal recessive disorder
Which protein is the hereditary hemochromatosis allele affecting?
Homeostatic iron regulatory protein (HFE)
What effect happens due to dysfunctional HFE protein?
Excess iron absorption
