8-26 Genetic Variation

Question 0

1) IVS
2) What does “g” mean?
3) What does “m” mean?
4) What does “c” mean?

Answer 0

1) IVS = Intervening sequence =donor splice site –>INTRON MUTATION
2) g= genomic DNA
3) m= mitochondrial DNA
4) c= cDNA “Complimentary DNA”

Question 1

1) Interpret Gln43X

2) What Mutation type is this?

Answer 1

1) Protein Level/Glutamine AA at position 43 on chromosome has UNEXPECTED STOP CODON (X) placed aftrward
2) Missense/nonsense mutation

Question 2

MORE CG promoter sequences= ___[INC/dec] chance of mutations

Answer 2

INC CG sequences= INC chance of mutations

Question 3

1) Maternal gamete mutations rates depend on what?
2) These “Mom” mutations rates are preceded by ___ mitotic divisions which _________.
3) At what age in Mom does the risk for nondisjunction start to INC?
4) What type of Trisomies can be directly inherited from MOm?

Answer 3

1) Maternal mutation rates depend on amount of time gametes are in Meiosis 1
2) “Mom” mutations are preceded by 22 mitotic divisions which lead all the way up to the primary oocyte stage
3) At PUBERTY risk for Nondisjnction INC with age in Moms
4) Trisomies 13, 18 and 21 are all maternally inherited

Question 4

What’s the rule of thumb for Gender bias mutations?

Answer 4

Point mutations=From DAD [ex. achondroplasia]

indels (Insertion or Deletion)= come from MOM

Question 5

1) By 25 y/o, how many mutations are occurring in each sperm of [DAD]?
2) How many sperm are deleterious at 25 y/o and how will this change with age?

Answer 5

1) 180 mutations/sperm at 25 years old
2)at 25, 1 out of 10 sperm are DELETERIOUS
(1/2000 TOTAL!) and gets worst as you age—->
xxxxxxxx1 out of 3 sperm deleterious by the time your 60

Question 6

*Non-Disjunction in Meiosis 1 = ____daughter cells are affected

$$NOn-Disjunction in Meiosis 2= _____daughter cells are affected

Answer 6

*ND in M1= ALLLL DAUGHTER CELLS AFFECTED

$$$$ND in M2= ONLY 2 of the daughter cells are affected

Question 7

Why does the mutation odds increase from eggs for women?

Answer 7

Because the longer the eggs sit in Meiosis 1= INC chances for mutation

Question 8

What are two characteristics for inheriting germline mutations FROM MOM?

Answer 8

1. Large deletions likely to occur from unequal crossover

2. Developing eggs will have Sister Chromatids inside exchanging material during meiosis

Question 9

Definition of Haplotype:

Answer 9

Haplotype= group of alleles within a gene (such as the MHC cluster) that are on a single chromosome and usually inherited together asone since they’re closely to one another

Question 10

MHC class 1 molecules are expressed by _______

Answer 10

MHC Class 1 are expressed by ALL LIVING CELLS

Question 11

MHC Class 2 molecules are expressed by ______

Answer 11

MHC CLASS 2 are ONLY EXPRESSED by PROFESSIONAL antigen presenting cells

Question 12

1) Having a blood type of [AB] means what physiologically?

2) What is the Mode of Inheritance for the blood type [AB]?

Answer 12

1) Having [AB] means you have both N-acetylgalactosamine(A sugar) + D-galactose (B sugar) present at position 4 of penultimate H-antigen of RBC
2) [AB] = CO-DOMINANT

Question 13

1) Having a blood type of [A] means what physiologically?

2) What is the Mode of Inheritance for the blood type [A]?

Answer 13

1) Blood type [A] means you ONLY have the N-acetylgalactosamine present on position 4 of the penultimate H-antigen of RBC
2) [A} = Dominant

Question 14

1) Having a blood type of [B] means what physiologically?

2) What is the Mode of Inheritance for the blood type [B]?

Answer 14

1) [B] means there is a D-galactose sugar on the 4 position of the penultimate H-antigen of RBC
2) [B] mode of inheritance = Dominant

Question 15

1) What is {Rh} factor?
2) What’s the mode of inheritance for Rh+ people?

3)Which is more common between Rh+ and Rh-

Answer 15

1) a factor from Chromosome 1 in which an Rh-D polypeptide is placed on the surface of the RBC if Rh+
2) {Rh+} ..MOi = Dominant
3) because it’s the Dominant mode of inheritance Rh+ is more common!

Question 16

Why are Siblings a better way to go for transplants then Parents?

Answer 16

Disregarding crossing over, Siblings have a 25% chance of sharing both alleles for the MHC haplotype with other siblings=better donors!
Parents only share 1 allele for this haplotype with their kids.

Question 17

What do these all represent:

[ p^2 + 2pq + q^2 = (p + q)^2

Answer 17

p^2 = The Statistic or Dz Frequencey for Homozygous DOM

p by itself= allele frequency for DOM

Question 18

HLA (human leukocyte antigen) [3]

Answer 18

1)HLA gene encodes for proteins that works within the MHC complexes to present pathogenic peptide pieces on the cell surface so immune cells can recognize->KILL

2) Mutations in HLA gene is liked to autoimmune dz
3) MAJOR cause of organ transplant rejections

Question 19

What are the assumptions that must be MET in order for u to even begin using the Hardy-Weinberg Equilibrium??

Answer 19

“RNNL have to bet said Hardy!”

1) RANDOM MATING (no pref. based on phenotype)
2) NO MUTATIONS
3) NO GENETIC SELECTION(all genotypes can mate and reproduce)
4) LARGE POPULATION

Question 20

1)What does a 20% fitness [f] indicate?

2) How is this related to new mutation frequency [s]?
3) What is the formula for “s”?

4)What happens if [f= 0]…..

Answer 20

1) 20% fitness [f=.20]means only 20% CAN PROCREATE :-/=not good
2) 20% fitness means 80% of mutant alleles CAME FROM NEW MUTATIONS and [s = .80]

• (s=1-f)* “so 1- 0.20 = 0.80”
  4) If [f=0] then the disorder is GENETIC LETHAL :-(((((

Question 21

Stratification

Answer 21

when a subpopulation remains genetically separate from the overall population<—happens when RANDOM MATING is NOT carried out smh

Question 22

1)What does a 20% pt fitness [f] indicate?

2) How’s this related to selection coefficient [s] (__ __ ___)?
3) What is the formula for “s”?

4)What happens if [f= 0]…..

Answer 22

1)20% pt fitness [f=.20]–>only 20% of those pt with that dz CAN PROCREATE :-/=not good

2)20% fitness means 80% of mutant alleles CAME FROM NEW MUTATIONS and [s = .80]
$selection coefficient=[s] –>new mutation frequency

• (s=1-f)* “so 1- 0.20 = 0.80”
  4) If [f=0] then the disorder is GENETIC LETHAL :-(((((

Question 23

What happens (OMG) if you have 3 possible alleles in 
Hardy-Weinberg?? wHat is the solving formula? [2] 

DRAW IT OUT!!

Answer 23

(p + q + r)^2

p2 + q2 + r2 + 2pq + 2pr + 2qr

Question 24

Polymorphisms and rare variants (alternate genotypes inside a population) can be caused by…..[5]

Answer 24

• SNP/2 alleles=single nucleotide polymorphism
• Indel/2alleles= simple insertion or deletion
• CNP/2 alleles (Copy # Polymorphism)=BAD!=HUGE REPEAT SEQ.s GO MISSING AND IS DIFFICULT TO DETECT
• STRP/5 or more POSSIBLE MUTANT ALLELES that can result= Short tandem repeat seq.[2-5 nucleotidesand 5-100 copies of the repeat segment]–>EXAMPLE: HUNTINGTON!
• VNTR/5 or more POSSIBLE MUTANT ALLELES= Variable # tandem repeat seq.

Question 25

Polymorphisms and rare variants (alternate genotypes within a population) can be caused by…..[5]

Answer 25

• SNP/2 alleles=single nucleotide polymorphism
• Indel/2alleles= simple insertion or deletion
• CNP/2 alleles (Copy # Polymorphism)=BAD!=HUGE REPEAT SEQ.s GO MISSING AND IS DIFFICULT TO DETECT
• STRP/5 or more= Short tandem repeat seq.
• VNTR/5 or more= Variable # tandem repeat seq.

Question 26

1) Describe VNTR (___ ____ ___ ____) in relation to minisatellite repeats and DNA fingerprinting.
2) How is VNTR detected?

Answer 26

1) VNTR(Variable # Tandem Repeats) combines to form MINIsatellite repeats of 10-100 ncleotides in variable #s.
* *You have to probe [od 13 VNTR loci] for fingerprinting.

2)VNTR is TOO LARGE for PCR amplification–> so has to be detected with Southern Blot Probes Dude!

Question 27

1) Between STRP/microsatellite and VNTR/MINIsatellite which is more commonly used for forensics and mapping genes?
2) Why is this?

3]HOw is STRP/microsatellite detected?

Answer 27

1)STRP/microsatellite is used more for Forensics&mapping genes!

2)STRP/microsatellite is more frequent and more polymorphic
[70% of people will be heterozygous for any microsatellite]

Question 28

Genome mutations

Answer 28

Mutations that involve a change in the NUMBER of chromosomes (i.e. Anueploidy)

Question 29

Chromosomal mutations

Answer 29

involve inversions or translocations that affect only the chromosome

Question 31

You would use (g)=genomic DNA when a sequence…. [2]

Answer 31

(g)=genomic DNA and you use this in coding when a sequence INCLUDES INTRONS [IVS] becuz it hasn’t been cleaved yet

exons only are for cDNA!!!

Question 32

Linkage Disequilibrium

Answer 32

there are only a certain number of possible haplotypes that are possible for one ethnic group

Question 33

What are the 2 mechanisms in which you can obtain an HLA-associated Dz

Answer 33

1. Functional unwarranted antigen presentation tht will ultimately lead to autoimmune dz/infection
2. HLA haplotype genome cluster mutation

Question 34

Explain how X-linked recessive genes are related to genotype frequencies for Males vs. Females
[Draw it out]

2-What’s a good example of this?

Answer 34

Males: X-linked recessive= just [q] = statistic of dz // and
just [p]=Normal Guys who don’t have it(like Color blindness!)

Females:X-linked recessive= 
XnXn=p^2= NORMAL
XnXa= 2pq = NORMAL STILL
XaXa = q^2 = affected!!!!!
*Normal Total = p^2 + 2pq

Question 35

Selection (such as balanced polymorphisms) against Dz that are _____ traits really makes NO real difference.

Answer 35

Selection(like balanced polymorphism) against Dz that are RECESSIVE makes NO Difference really!