Genetic Composition and multigene families Flashcards
What is the purpose of Genetic complementation tests? What do these tests reveal?
Genetic complementation test : Allow us to tell if 2 different mutations affect the same gene or different genes.
These complementation tests can reveal which mutations are alleles of the same same gene
Ex: observing how fruit flies vary in eye color (red eye vs white eye; seeing if different mutations cause it)
(side note: a way of learning how groups of genes work together to control each human disease )
How is a fruit fly complementation test done? How does it differ mutants in the same gene vs different gene?
Fruit fly complementation test:
if two mutations are recessive, then we can tell if same gene by doing cross. Ex: take Cn male (give fly red eyes) x 80 c female (give red eyes) then all offspring should have red eyes, as product will be cn^2/80c and kids will be defective for other gene.
-Hence, if mutations are in the SAME gene (1 mutant x another mutant), you will still have offspring with HOMOZYGOUS MUTANT
-If Mutants are in DIFFERENT genes (ex: cross cn male (red eyes), x Of female (red eyes) the offspring will all NORMAL because you get children with Cn/normal allele of cn gene (received from mom) and normal allele/Of alele (from dad)
these offspring will have dark-red-eyes.
List the reasons for why Complementation tests are difficult with humans
Complementation tests are difficult with humans:
-We can’t carry out deliberate complementation tests with people
-Sometimes family pedigrees fortuitously let us test for complementation
-Nowadays, gene sequencing often resolves problems, but it requires knowledge of which gene sequences might be affected
-sometimes other methods are possible
What is Xeroderma pigmentosum? What are its symptoms?
Xeroderma pigmentosum: genetic disease that can be cause by a large number of genes that are all required for DNA repair
Symptoms:
-Skin and eyes are very sensitive to sun.
-extensive freckling
-Development of solar keratoses and skin cancers
-Patients usually die at a young age from malignant cancers (not caught in time and removed)
Explain how sunlight affects DNA and how it relates to the medical disease Xeroderma pigmentosum
Sunlight damages DNA by forming THYMIDINE DIMERS
if you have 2 thymines together, UV can add enough energy where the thymines will form a chemical bond to each other.
DNA Repair enzymes will not know what to do with this dimer, in order to prevent damage, hence this issue needs to be fixed (though Normal Excision Repair)
Explain How Thymidine Dimers can be fixed?
Normally, Thymidine Dimers can be fixed through Normal Excision repair:
-if thymine dimer forms, Enzymes can recognize dimer and make little cuts on either sides of dimer.
-The pieces that are cut will be excised and degraded, leaving a little pieces of signal stranded DNA
-The other strand can be used as a template for repair and DNA polymerase will synthesize a good strand, and fill in the gap in strand
- DNA ligase will seal these pieces together.
Hence Normal excision Repair is beneficial in removing Thymine dimers from DNA and preventing mutations
Why can’t these Dimers be fixed in xeroderma pigmentosum patients? What happens as a result?
-Normal cells recognize, cut out and repair these lesions in DNA
-patients with Xeroderma pigmentosum CANNOT carry out these repairs
-As a result, XP patients Accumulate many new mutations in tissues exposed to UV light
In terms of genetics, what kind of mutations causes Xeroderma pigmentosum?
RECESSIVE MUTATIONS
When viewing pedigree, How can we tell if these families (family A and Family C) have the same defective gene? What is a solution?
To tell if the families have the same defective gene:
-We cannot ask patients to have children together for us to observe (no complementation test with people)
-However, Xerdoderma pigmetnosum has a cellular phenotype that we can study: Cells CANNOT Repair thymidine dimers*
-Thus, We can FUSE cells from two people and study their phenotypes in Petri dishes
(they can do cell by cell crosses; take cells from people with XP and fuse them)
Compare and contrast how to determine if a different XP patients have the same XP or Different XP defect based on hybrid cells ( fused cells of XP patients)
If the Hybrid cells (fusion of two XP patient cells are) DEFECTIVE, both patients have the SAME XP defect (not able to do DNA repair)
-If the hybrid cells are NORMAL (two good copies of gene) , each patient has DIFFERENT XP defect (DNA repair can occur)
What was the significance of the XP studies and repair of DNA?
These studies showed that EIGHT different XP genes cooperate to repair DNA and that *ALL Eight need have a NORMAL copy for repair to work
(These Xp genes can recognize and repair thymine dimers; also 8 different mutations that can cause Xeroderma pigmentosum)
What do Alport Syndrome and Thin Basement Membrane Nephropathy have in common?
Alport Syndrome and Thin Basement Membrane Nephropathy are related genetic disorder, since they have REDUNDANT genes (2 copies of a gene on each chromosome). Hence, if 1 copy of gene is bad, still have other one that is working.
they also have duplicated genes.
what is Alport syndrome and its major symptoms ?
Alport syndrome: inherited genetic disorder that damages vessels in kidneys and causes eye and hearing abnormalities.
Major Symptoms: ;
-Blood in the urine (hematuria)
-Kidney disease
-Hearing loss
-Eye problems (like bulging of lens capsule)
Molecular problem is DEFECTIVE Collagen IV.
-Collagen is a fiber that strengthens tissues.
(collagen fiber- gives form to skin, cartilage and help keep shape)
What is the main role of the kidney ?
Kidney FILTERS blood through the glomeruli
blood comes in and passes up through kidney and be filtered blood comes out.
(in nephron, unfiltered blood comes in and then gets filtered out through glomerulus)
complex plumbing for waste to come out.
What would happen to the structure of Glomerulus if structural proteins were not working well?
If structural proteins that help hold shape of nephron together and glomerulus; the glomerulus itself would become abnormal and would not work as well, leading to symptoms described with Alport syndrome (blood in urine, kidney disease)
What will happen to glomerular wall with loss of Collagen IV? Compare the appearance of the all in normal, vs thin basement membrane lesion and Alport syndrome
The Loss of Collage IV can damage the glomerular wall
-Normal GBM (glomerular basement membrane) ; normal shape and size
-Thin basement membrane Lesion - Abnormally Thin GBM
-Alport Syndrome: Abnormally split and Laminated GBM (glomerular wall largely splits and separates)
Describe the structure of different collagen fibers
Structure of collagen fibers;
1) Chain: three fiber strands
2) Procaollagen - three fiber chains twisted together to form thicker structure
3) Tropocollagen- three different chains of pro collagen wrap together like string to make solid and tough structure, which can hold things together
fibrils (multiple tropocollagen combined) interact with other collagen fibers to make dense structures that give tissue form and strength.
How many genes encode the adult Collagen IV alpha chain? Why is this significant? Where are they each located?
THREE Genes encode the Adult Collagen IV Alpha chain
(several kinds of genes, you make different kinds of proteins at different stages of development )
Collagen 4A3 and Collagen 4A4 genes are both on Chromosome 2 next to each other. Chromosome 4A5 gene is on chromosome X. All of these Collagen genes contribute to making the Adult Collagen IV.
Which genes encode the Embryonic GBM chain?
Collagen 4A1 and Collagen 4A2 that are both on chromosome 13 encode for Embryonic GBM chain
