MJ slides lecture 1.2 Flashcards
1.2
1) Define Single Nucleotide Polymorphisms (SNPs)
2) What does it usually have?
3) Where do most occur?
1) Multiple versions of nucleotide base at single location “substitution”
2) Two alleles
3) Non-coding portions of DNA
1) More than 100K ________ SNP’s have been discovered
2) Half of these do not alter the amino acid sequence (called “________________”)
3) Those that alter amino acid sequence are “________________”
1) exonic
2) synonymous
3) nonsynonymous
List 2 significant changes caused by Single Nucleotide Polymorphisms (SNPs)
1) Altering or introducing a stop codon
2) Altering a splice site where introns/exons are altered
1) How many base pairs can Indels (Insertion / deletion polymorphisms) occur in?
2) How many alleles do most “simple” indels have? What does this mean?
3) What is another type of indel besides “simple”? What are these?
1) as few as one base pairs, and as many as ~1000
2) Two; basically, the presence or absence of the inserted/deleted segment
3) “Microsatellite”; have multiple short repeats of the inserted segment
1) Give an example of a microsatellite indel
2) What does this make? What are these called?
1) Instead of a single instance of TGT, you see TGTTGTTGTTGTTGT
2) Many different alleles, depending upon how many repeats there are. Called STR polymorphisms
(“short tandem repeat”; tandem means “length”)
1) What can be unique and used to identify individuals and families
2) Microsatellite loci are known to researchers and number in the _____________
1) Microsatellite indels
2) thousands
What is involved in DNA fingerprinting?
Microsatellite indels
1) Mobile Element Insertion Polymorphisms consist of what? Give examples
2) What happens to these? What is this called?
3) What is this process called? What is it similar to?
1) Repetitive elements (think Alu and LINE)
2) Transcribed into RNA, then reverse transcribed back into the DNA code, but at a different locus; retrotranscription
3) Insertion (i.e. transposition); processed pseudogenes
1) What are Copy Number Variants?
2) What are the largest of these called?
3) The allelic variation comes from what?
1) Up to hundreds of thousands of base pairs long
2) “segdups” (segmental duplications)
3) The number of copies
Regarding copy number variants:
1) True or false: The larger the number of copies inserted, the more variation
2) If these do include genetic material, what can they do? Why is this a big deal?
1) True
2) Alter gene dosage; it’s like giving yourself multiple copies of a given gene
1) Define inversion polymorphism
2) When does it often happen?
1) A portion of the sequence is “flipped around”
2) During recombination
(recombination is the same thing as “crossing over”)
1) What are the two general types of inversion polymorphisms?
2) What can inversion polymorphisms result in?
1) Pericentric (includes centromere) vs paracentric (doesn’t)
2) Duplication or deletion of DNA located between regions of homology, causing genetic disease
1) Many chromosome mutations produce a change in the number of what?
2) What is this caused by?
3) What does this result in? Maternal or paternal?
4) In what chromosomes is this nearly always lethal? Why?
1) Chromosomes
2) Chromosome missegregation during meiosis I or II
3) Aneuploidy; maternal or paternal (often maternal)
4) autosomal; “gene dosing”
1) Give 3 examples of regional mutations. When do all of these predominantly happen?
2) Give an example of where this can happen
1) Large duplications, deletions, or inversions; during recombination
2) At spontaneous breaks in the DNA
Single gene mutations:
Include base pair substitution, indels, can occur in what two ways?
1) During DNA replication
2) After failure to repair damaged DNA
Frameshift mutations: When the insertion / deletion number of nucleotides is not a multiple of three, what happens?
Everything downstream is messed up
1) Define placental mosaicism
2) Define somatic mosaicism
3) Define germline mosaicism
4) When does segmental mosaicism occur? Give an example
1) In the extraembryonic tissue but not in baby
2) In the body and not gametes
3) In the germline only
4) Only part of the body is affected; neurofibromatosis 1
True or false: Mosaicism might and will occur due to X-inactivation
True
List 4 different types of mosaicism
1) Placental
2) Somatic
3) Germline
4) Segmental
1) Define hemochromatosis
2) What is its penetrance and expressivity?
3) What inheritance pattern does it have?
1) Disease of iron overload resulting in mutation of the HFE gene
2) Incomplete penetrance and variable expressivity
3) Autosomal recessive inheritance pattern
Single nucleotide substitution or “point mutation” may lead to one of what two mutations?
“Missense mutation” or “nonsense mutation”
1) When mutations alter the genetic code in a “minor way”, they’re _____________ mutations, though they need NOT always result in change in function of the protein.
2) What may be wrong with the protein?
1) missense
2) May not work properly, may be unstable and rapidly degraded, or may not localize in the right spot in the cell
1) What type of nucleotide substitution mutation disrupts the code enough that the protein is unusable?
2) What does this frequently occur due to?
1) Nonsense mutations
2) Premature or otherwise altered “stop” codon
1) The change in the amino acid sequence in sickle cell anemia causes what?
2) What is the change in the AA sequence?
1) Hemoglobin molecules to crystallize when O2 levels in the blood are low. RBCs get sickle and stuck in small blood vessels.
2) TA to AT changes glutamic acid to valine
1) What kind of mutation is achondroplasia? What does this mean?
2) Is it dominant or recessive? What does this mean?
1) Gain of function mutation; altered gene product has new function
2) Autosomal dominant; when you’ve got it, you display it
1) Is achondroplasia a missense or nonsense mutation? Describe where it comes from
2) Achondroplasia is a De novo mutation in germ line of one parent. Which parent is it usually? Why?
3) Will people with achondroplasia mutations always display it? Explain
1) Missense mutation; resulting from substitution of G > A or G > C, which results in the substitution of one Glycine for Arginine
2) Happens almost exclusively in the paternal side because DNA in sperm has undergone far more replication cycles than DNA in the ova
-Greater opportunity for de novo errors due to the sheer number of replications
3) Yes, bc it’s an autosomal dominant disorder
1) Body stores of iron determined by what?
2) What regulates these stores? Where is it made?
3) What does a mutant HFE gene do?
1) Dietary absorption from enterocytes in small intestine, and release of iron from macrophages that phagocytize RBC’s
2) Iron response hormone, hepcidin, which is synthesized in the liver and released to block further iron absorption when supplies are good
3) Inhibits hepcidin signaling, disinhibiting enterocytes and macrophages to release iron
1) What two ways can you get hemophilia A?
2) What is the expressivity?
3) What is it linked to?
1) Intrachromosomal recombination and Movable element insertion
2) Variable expressivity
3) X-linked
1) True or false: Factors in the clotting cascade are present in circulation at all times, though inactive
2) What do clotting factors do when sequentially activated? Which two in particular amplify this cascade to accomplish this?
3) Deficiency in these two factors can be caused by what two things?
4) What can account for each of these?
1) True
2) Fibrin clot; factors VIII (8) and IX (9)
3) Hemophilia A or B respectively
4) Mutations in F VIII and F IX genes
