L1+2 (intro) Flashcards
Why is it said diseases are not inherited but have genetic components
Because there are other factors which affect likeliness like epi genetics and environment
What are complex diseases
Where more than 1 alleles/variations/mutations work alone or together to cause a risk of disease
(POLYGENIC)
What are the 3 models of a genetic disorder
Chromosomal - structural or number changes (less than 1%)
Mendelian - 1-4% monogenic mutations
Complex - polygenic (70-95%)
Give some Mendelian mutations types and a disease example of each
Point mutation/substitution (in sickle cell Hbb gene glycine to valine)
Deletion (f508 in cf)
Insertion (Huntington has CAG repeats)
What 3 Mendelian inheritance patterns do these diseases follow
Recessive , dominant or sex linked
Eg cf is autosomal recessive so needs both copies
When does a Mendelian disorder have 100% penetrance
If it is a dominant disease
Why does environment have weak/no impact on if you get the disease (still affects progress and outcome)
Dominant allele = always have phenotype
What is Mendels law of segregation
During gamete formation, 2 alleles from each parent segregate into each gamete (get 2 copies m and f)
What is independent assortment whcih was discredited due to linkage (where genes on same chr inherited together)
Alleles for different traits segregate indep from eachother
What is the difference between somatic cell mutation and gamete mutations
Gamete are passed onto progeny whereas somatic aren’t but can cause some malignancy or congenital diseases
What is the difference between de novo and mosaic somatic mutations (not Mendelian as not passed on from parent)
De novo is usually mutation early prenatally so present in most cells and all of life
Mosaic happens later in life in some cells meaning some are wt some are mutant cells
Both are not passed on
You can get inherited mutations from both or 1 parent which is then in all cells and passed onto next gen. How is gamete mutations different if it’s still an ‘inherited’ mutatioj
It isn’t Mendelian as it is not a disease present in parents eg trisomy Down syndrome. But is also present in life
What is an example in cf Mendelian where another gene modifier exist other than the CFTR gene = Mendelian vs complex overlap
A tgfb1 variant which has been associated to affect severity of the lung disease
Do complex/multi factorial diseases follow Mendelian inheritance patterns
No because there are many susceptibility loci/snps and depends more on environment interaction too
How can penetrance vary in complex disease
Can be low penetrance if someone has minor alleles that rely on environmental interaction
Also can be reduced penetrance
Some do still have high penetrance if have major susceptibility alleles
Which illness has 80% penetrance (AKA REDUCED PENEtrance)
Familial breast cancer if you have the germ line mutation in brca genes
Do common variants in popn usually cause penenteance
No it is a combination with some rare low freq variations which can increase risk/ penentrance
Give the example of how environment ca n still impact Mendelian diseases
P.aeruginosa exposure more in hot climates which exacerbates Cf
Manganese can interact with Huntingtin mutant gene and reduce the phenotype
What makes up most of genetic variation (90%)
SNPs which can then cause disease susceptibility and impact treatment options
What do studies on SNPs and disease not take into account
Structural genetic variations like copy number variants which impact the gene dosage causing disease
And other issues like deletions, inversions and translocations
Why are SNPs evolutionary
Happened mutations due to selective pressures. Those advantageous SNPs were passed on
How many SNPs exist
85 million
What is the difference between a mutation and snp
For an allele to be an snp the minor allele frequency in the popn needs to be over 4% (how many people have the snp minor allele)
For a mutation the number is below 1% minor allele frequency (must be rare)
Give some examples of how SNPs can be functional (alter genes)
In promoter region- affect tf binding and gene exp levels
In intron- could affect splice site so mrna processing
In 3’5’ utr regions- affect mrna stability
In coding region - missense or nonsense
Intergenic regions - affect silencer or enhancers affecting gene exp
