Genetics Flashcards
What is the difference between mitosis and meiosis?
Mitosis- more copies with the same # of chromosome (growth)
Meiosis- reproduction
What are genes? Genome? How many genes in humans? What is an allele?
Genes- encode basic info to make proteins
Genome- full set of genes in each cell of an organism
25,000
Allele- alternate forms of the same gene
What is the difference in the DNA responsible for?
Biological diversity- disease, disease susceptibility, different response to drugs
What is a SNP?
Single nucleotide polymorphism…different single base pair.
What is the difference between hereditary disorders and congenital?
Hereditary- transmitted through the germline
Congenital- present at birth
What are the 3 types of classifications of human genetic disorders?
- Mendelian- mutations in single genes, highly penetrant
- Complex multigenic disorders- involves multiple genes, complex, common, genetic heterogeneity (mutations in several locations have impact on same trait/disorder))
- Chromosomal disorders- changes in autosome or sex chromosome number or structure, highly penetrant, not common
How are mendelian disorders transmitted?
Autosomal dominant (heterozygous possible, variations in penetrance and expressivity) Autosomal recessive (homozygous, complete penetrance) X-linked: all sex-linked are X linked
What is the difference between expressivity and penetrance?
Expressivity- depending on the severity of the disorder, different phenotypes can develop
Penetrant- if you have the genetic mutation, how likely you are to express the trait.
What types of mutation are there?
Permanent changes in DNA via meiosis or mitosis
Deleterious
What is a point mutation? What are the subtypes?
happens at a specific base pair silent- doesn't change phenotype missense- gives a different AA nonsense- stop codon *if it is in a non-coding region, can still alter transcription (promoter, enhancer) or RNA splicing
What is a frameshift mutation?
Extra AA is put in or taken out, which throws off all subsequent triplets
Tay-Sachs- hexaminodase gene mutation
CF- CFTR gene mutation
What is a trinucleotide repeat mutation?
characterized by repeat of 3 base pair sequence
Fragile X-repeat of CGG in gene FMR1
HD- repeat in CAG in huntington
*greater number of repeats=earlier onset, generally
What method is used to look at specific DNA sequences?
Sequencing: denaturation, annealing, extension
Also FISH for fluorescently labeling sequences
What are the three categories of proteins affected by mutations?
- Structural proteins- widespread secondary effects: hereditary spherocytosis, osteogenis imperfecta
- Enzymes-reduced activity or amount of enzyme
- Receptor and Transport system- CF, familial hypercholesterolemia
What syndrome involves elastic fibers?
- Marfan- mutation in gene encoding protein Fibrillin 1
- leads to fewer microfibrils and weak elastic fibers. -Autosomal dominant.
Where is cartilage found?
skin, ligaments, joints, tendons, cornea, bone, organ and blood vessel walls, the gut, IV disc
What is Ehlers Danlos Syndrome?
- Heterogeneous mutations disrupt the structure, production, and processing of collagen
- dominant negative (incorrectly made collagen dominates the correctly made)
- Contortion artists
What are the causes of lysosomal storage diseases? What are the types?
enzymes not being properly stored or made I cell Tay Sachs Gaucher disease Nieman Pick Disease
What causes Tay Sachs?
- lysosomal storage disease
- Tay Sachs- gangliosides accumulate in the brain
- mutations in hexosaminidase A, include bp insertions, deletions,point mutations, and more complex patterns
- autosomal recessive
What causes Gaucher Disease?
-lysosomal storage disease
-mutation in GBA=accumulation in phagocytes
type 1 (some enzyme activity)
type 2 (no enzyme=early death)
type 3 (in between 1 and 2)
What is Nieman Pick Disease?
-lysosomal storage disease
accumulation of sphingomyelin (lipid)- lack of acid sphyingomyelinase- leads to FOAM cells
type A (no enzyme activity) type B (10% enzyme activity) type C (defect in lipid transport-more common)
-Autosomal recessive
What is Pompe Disease?
- lysosomal storage disease
- accumulation of glycogen due to acid-alpha-glucosidasae enzyme deficiency
- Autosomal recessive
What is Familial hypercholesterolemia?
- defect in gene endcoding LDL receptor so LDL cannot be transported into cells
- autosomal dominant
What is the underlying defect in CF?
CFTR gene mutation so Cl- cannot be transported and Na transportation is also affected
-Autosomal recessive
What is I cell?
- Autosomal Recessive
- Lysosomal Storage Disease
- Mutation in phosphotransferase, which marks proteins with mannose so they can be transferred into the lysosome
What is dwarfism?
- mutation in fibroblast growth factor receptor
- Achondroplasia (homozygous is lethal) and Thanatophoric Displasia (heterozygous is lethal)
- Autosomal dominant
What is Sickle Cell disease?
- mutation in hemoglobin= sickle shaped cells
- heterozygous carrier has advantage in fighting malaria
What is heomphilia?
- mutation in clotting/coagulation.
- sex-linked
- Recessive
When is a karyotype and when can it be used?
- total # of chromosomes to diagnose abnormalities
- especially recommended for advanced maternal age, repeated miscarriages, familial risk
- used to diagnose numerical and structural disorders
What are the types of aneuploidy?
Down syndrome (trisomy 21) Edwards syndrome (trisomy 18) Patau syndrome (trisomy 13)
What is mosaicism?
mitotic error, especially in sex chromosomes= some normal cells and some abnormal cells
What are the types of structural abnormalities?
deletions, duplications, inversion, translocations, and robertsonian translocations
Why don’t females experience any symptoms from having 2 Xs?
Lynoization- inactivation of one of the Xs (at least part of it). Happens early and randomly in development- irreversible except for the germline.
What is Klinefelter syndrome?What is turner syndrome? What is trisomy X?
Extra X in males (90% non-dysjunction, 10% mosaicism).
Only one X in males.
Female with 3 Xs don’t see any physical changes but increased risk of learning disability
What is genomic imprinting? What are the syndromes associated with it?
selective inactivation of either maternal or paternal allele.
Paternal silencing= Prader-Willi
Maternal silencing=Angelman Syndrome
What is epigenetics?
Modifications leading to gene silencing.
- Methylation of cytosine in CpG rich regino upstream of imprinted genes lead to chromosome condensation.
- De-acetylation of histones so nucleosomes condense into tightly bound structures.
