fundamental molecular biology

Question 1

the rate of spontaneous mutations

Answer 1

always occur but at a low rate

Question 2

the four effects mutations have on your genes

Answer 2

silent- does not have a final effect
nonsense- give arises to a stop codon (bad)

missence = non conservative - substitution of base pairs producing a different amino acid with different properties (non functional e.g sickle cell)
conservative- different amino acid with similar properties (functional)

nonsence- presence of a stop codon

frameshift- deletion or insertion of DNA sequence (bad).
adding 2 bps (or any number of bps not a multiple of 3) constitutes a frameshift mutation because the triplet nature of codons means that the amino acid sequence will change if the reading frame is moved up or down the sequence.

Question 3

outline with examples how recessive loss of function mutations affect phenotype
-e.g. mutation of tyrosine gene,
albinism pathway in OCA1 gene

Answer 3

most loss of function mutations are recessive as the gene is works less/ no activity.
can affect the phenotype by too much substrate or too little product
example-
OCA1 gene means tyrosinase enzyme mutants have severe albinism.
albinism pathway mutations of tyrosinase gene which is crucial for melanin production. individuals have two muted copies of the gene, leading to reduced or absent melanin. resulting in lighter skin, hair, nails.
less melanin= more prone to skin cancer

Question 4

explain gain of function dominance

Answer 4

rare mutation where mutation is dominant rather than recessive.
can be incomplete dominant- having one mutant allele is enough not to be normal.

Question 5

why most mutations are recessive

Answer 5

as it requires two alleles for a individuals to exhibit a trait

Question 6

why mutations can be dominant

Answer 6

due to gain of function mutations (can be complete or incomplete dominate)
gain=
1)more of a normal function= more active enzyme or produce more protein
2)new/ abnormal function= unrelated to what the normal gene does. presence of WT makes no difference.

Question 7

examples of dominant gain of function mutations

Answer 7

normal function= achondroplasia (dwarfism)
new/abnormal function= huntintons- part of gene contains a microsatillite

Question 8

explain the importance of homologs (orthologs and paralogs)

Answer 8

Homologous genes are genes that share a common evolutionary ancestor. They may be found in different species and can show similarities in sequence and function. eg cat and leopard.
Orthologs and paralogs are terms used to describe relationships between genes based on their evolutionary history. (segments of DNA from homologous genes).
Orthologs is a result from speciation and retains similar function among species (gene divergence between species)
paralogs result from gene duplication (gene divergence within a species). May have similar, diverging, or completely different functions.

Question 9

what is indwells insertions and deletions

Answer 9

can be loss of function or frame shift.
most do not effect gene function as it occurs outside gene introns

Question 10

what is variable number tandem repeats (VNTR) and what are the two types with an example?

Answer 10

short sequences of DNA that are repeated multiple times in a row.
micro satellite are short tandem repeats. eg huntintons disease part of the gene contains micro- satellite.
mini satellite and long tandem repeats

Question 11

what is copy number variants (CNV)

Answer 11

are segments of DNA that vary in the number of copies among individuals within a population due to types of duplication and deletion events

Question 12

outline the nature and use of single nucleotide polymorphisms (SNPs)

Answer 12

most common type of genetic variation amounst people. each SNP represents a nucleotide.

Question 13

the hardy Weinberg equilibrium calculation to test allele frequency if population is changing overtime

Answer 13

p+q=1
p2+2pq+q2=1
p2 is the frequency of homozygotes in pp population
q2 is the frequency of homozygotes in qq population.
2pq is the frequency of heterozygotes in the population

Question 14

what does the H-W equation predict

Answer 14

see if the allele frequency is stable from one generation to the next ie. the allele frequency does not change with the generations =
evolution is not occurring in the population.

Question 15

how will the population be if H-W equation is at obey

Answer 15

• population is randomly mated
  -population is not stratified
  -natural selection is not acting.
  if the sum equals 1 the population is not evolving

Question 16

the equation of allele frequency of allele A (p)

Answer 16

allele frequency= number of A / total

Question 17

how does each recessive mutation affect phenotype for
-albinsim
-cretinism
-alkaptonuria
-PKU

Answer 17

albinism= less/none product

cretinism= less/none product

alkaptonuria= more substrate

PKU= more substrate

(all the same- enzyme does not function well or at all)

Question 18

example of normal gain of function mutation
-achondroplasia (dwarfism)
-what mutation causes it and what mutation is it in?

FGFR3

Answer 18

one of two missence point mutation in FGFR3. it acts to inhibit slow limb growth.

Question 19

example of a lethal dominant mutation
-Huntingtons
-what mutant allele caused it

CAG and polyglutamine

Answer 19

CAG repeat gets longer , hence polyglutamine repeat in the protein=
toxic

Question 20

how must the human population obey for the HW equilibrium to be met?

Answer 20

-random mating
-homogenous population (not stratified)
-population has not recently been small
-mutation between alleles occurring at a low frequency.
-natural selection not occurring.

Question 21

explain the bitter taste process of TAS2R38

Answer 21

it encodes for a protein receptor. PTC present on taste buds of tough it activated through binding of a G protein cell receptor (GPCR)

Question 22

what recognition site does FNu4H1 restriction endonuclease use

Answer 22

GC ‘N’ GC

Question 23

what gene causes severe albinism and explain what causes albinism?

Answer 23

OCA1 gene means tyrosine enzyme mutants have severe albinsim
-caused by the inability of tyrosinase (substrate) to convert tyrosine into the pigment melanin. (product)

Question 24

what causes the phenotype phenylketonuria (PKU) and treatment ?

Answer 24

excess of substrate (phenylalanine).
damages brain development
treatment - low phenylalanine diet

Question 25

examples of mutations and what causes them?
-achondroplasia(dwarfism)+ melanism (black skin)
-alkaptonuria
-xeroderma pigmentosum

Answer 25

-dominant mutation- not lethal

-recessive too much substrate (causes black urine)

-DNA cannot repair itself

Question 26

what class of mutation are you least likely to see in a natural population?

Answer 26

dominant lethal mutation