fundamental molecules

Question 1

what is a genome sequence?

Answer 1

the order of nucleotide bases that make up an organisms DNA/RNA

Question 2

what is a mutation?

Answer 2

changes in the genetic material of a cell (or virus).
it is any heritable alteration in the genetic material.
in which genes change from one allelic form to another.

Question 3

what is an allele?

Answer 3

each of two or more forms of a gene that arise by mutation and are found at the same place on a chromosome (different version of same gene)

Mutation creates slightly different versions of the same genes, called alleles.
>mutation generates new allels

Question 4

what is a gene?

Answer 4

a genomic sequence (DNA/RNA) directly encoding functional product molecules, either RNA/protein.
- the gene is a union of genomic sequences encoding a coherent set of potentially overlapping functional products

Question 5

what generates the genetic differences which are required for natural selection to take place?

Answer 5

sex (recombination)
spontaneous mutation
**very low rate of spontaneous mutation (not zero), for human germ line - 200 new mutations in each human child

Question 6

how does the body try and lower net mutation rate?

Answer 6

through DNA repair

Question 7

what is a germ line cell?

Answer 7

gametes (sperm and ova) and the stem cells which divide to produce them.

Question 9

what is a somatic cell?

Answer 9

the cells in the body that aren’t germ cells

Question 10

what is the difference in mutations in germ-line and somatic cells?

Answer 10

germ-line cells have mutations passed on to next generation (low mutation rate)
somatic cells are a genetic dead-end, mutations not passed (higher mutation rate).

Question 11

what effect to most mutations have?

Answer 11

no effect.
most mutation affect regions that aren’t important (between genes/between exons).
most don’t change the phenotype
**unless they affect important parts (only 1-2% of genome)- key functional residues (e.g. the protein/RNA coding regions) or regulatory regions (gene expression/translation signals etc.)

Question 12

what do most genes encode for?

Answer 12

most genes encode proteins

Question 13

what are the different types of mutation?

Answer 13

frameshift mutations (insertion/deletion)
-mis-sense (results in substitution of one amino acid for another)
-non-sense (mutation creates a stop codon)

Question 14

are most mutations recessive or dominant?

Answer 14

most mutations even if they fall in important places are recessive. -can only affect phenotype when homozygous

Question 15

when do recessive mutation ‘show’?

Answer 15

on homozygous alleles.

Question 16

what do recessive mutations require?

Answer 16

‘inbreeding’
when two carriers reproduce.

Question 17

why is it beneficial to understand inheritance patterns?

Answer 17

-tell you something about how the mutation affects that gene
-tells you something about what the gene does
-suggest therapy/intervention strategies

Question 18

are most recessive mutations loss or gain of function?

Answer 18

loss.
partial or complete loss of function of one allele is recessive for most genes, then one functioning allele of the gene in a diploid organism is enough to appear/to be normal

Question 19

are most dominant mutations loss or gain of function?

Answer 19

gain. (most gain-of-function mutations are dominant)

Question 20

what is incomplete dominance?

Answer 20

• having one mutant allele is enough not to be normal (heterozygote)
• having two mutant alleles is worse/different again (homozygote)
  *one mutant allele is enough to change phenotype

Question 21

what is PTC?

Answer 21

phenylthiocarbimide.
- PTC tastes bitter to ~70% of the population

Question 22

why can some people not taste PTC (phenylthiocarbamide)?

Answer 22

the inability to taste phenylthiocarbamide is a genetic trait that varies in the human population.
gene TAS2R38 encodes for a protein receptor that mediates the perception of bitterness through a G protein-couples second messenger pathway; variations in the gene sequence leads to ‘non-taster’/’taster’ phenotypes; sequencing identified three nucleotide positions of TAS2R38 that vary within the human population (3 SNPs)

Question 23

what is PCR?

Answer 23

polymerase chain reaction.
it is a laboratory technique which amplifies a short segment of DNA/RNA

Question 24

what process occurs during PCR?

Answer 24

the DNA/RNA is heated to 94 to denaturation; cooled to 50-60 to allow primer to bind; heated to 72 to allow for extension
-this process is repeated 25-30 times

Question 25

what goes into a PCR?

Answer 25

-template to be amplified
-forward and reverse primers
-Taq DNA polymerase
-dNTPs
-buffer to maintain and provide Mg2+

Question 26

what is Taq DNA polymerase?

Answer 26

DNA polymerase which can work at high temperatures. extracted from the thermophillic bacteria; thermus aquaticus.

Question 27

what are dNTPs which are used in PCR?

Answer 27

Overall, the importance of dNTPs lies in their fundamental role in DNA synthesis, replication, repair, and cellular metabolism, making them essential components for the maintenance of genetic integrity and cellular functions, as improper or imbalanced dNTPs pools may lead to growth defects and oncogenesis.

Question 28

what is restriction endonucleases?

Answer 28

-restriction enzymes cut DNA at a specific nucleotide sequence (restriction site)
Restriction endonucleases are enzymes that recognize a specific DNA sequence, called a restriction site, and cleave the DNA within or adjacent to that site.

Question 29

what is the hardy weinberg equation?

Answer 29

p2 + 2pq + q2 = 1.
>genotype frequencies

> 0.36+0.48+0.16=1

p^2 = (GG) homozygous dominant
2pq = (Gg) heterozygous
q^2 = (gg) homozygous dominant

p + q = 1
>allele frequencies

p = dominant allele frequency G
q = recessive allele frequency g

Question 30

what are the 5 assumptions for the hardy weinberg equilibrium?

Answer 30

1. no selection
2. no mutation
3. no migration
4. large population
5. random mating

Question 31

does p = q in the hardy weinberg equilibrium?

Answer 31

no p doesn’t have to equal q.

Question 32

is the dominant allele frequency in a population larger than the recessive allele frequency?

Answer 32

dominant allele frequency doesn’t have to be larger than the recessive allele frequency
dominant alleles aren’t always the more common allele

Question 33

new de novo mutations are coming into the human gene pool every generation. the set of de novo mutations is unique to each individual, is shared across all the cells of their body, and is not shared with the genomes of their biological parents.
what is the most likely origin for any single de novo mutation?

Answer 33

> occurs in the germline cells of one of the parents

Germline mutations occur in either the sperm or ova (germinal cells) of an individual. If any of these mutated cell germinate, then that mutation will be passed onto the zygote and every cells of the resulting offspring will carry that mutation.
A mutation in a somatic cell of a parent would not affect the gametes of said parent and therefore would not be passed onto any children. If the mutation occurred in the multicellular embryo, then the acquired mutation would only be present in a proportion of the individual’s cells (all the daughter cells of the cell in which the mutation occurred) in a condition called mosaicism.

De novo mutations are new mutations that are not inherited from either parent and arise for the first time in an individual. These mutations can occur in the germline cells (sperm/egg cells) of one of the parents. When these germline cells undergo meiosis and contribute to the formation of a zygote, any mutations present in the germline will be passed on to the offspring.

Question 34

mutations in natural populations occur by spontaneous mutation and can be dominant or recessive. They can also have no effect on phenotype (silent mutation), can have a mild effect, a strong effect, or even be lethal.

which class of mutations would you least expect to occur or observe in natural populations?

Answer 34

Dominant alleles are more likely to affect phenotype than recessive alleles, as both homozygotes and heterozygotes will carry the associated trait, as oppose to simply homozygotes in the case of recessive alleles. Lethal alleles are the most likely to prevent an organism from passing on its genes during reproduction, as these genes cause the death of the organism that carries them. In other words, lethal alleles have the most detrimental effect on reproductive fitness.
Therefore, the least likely allele to occur in a natural population will contain a dominant, lethal allele.

Dominant lethal mutations are those that, if present in just one copy (due to the dominant nature of the allele), lead to the death of the organism before it can reproduce. As a result, individuals carrying such mutations would not contribute to the gene pool of the next generation, making them very rare in natural populations.

Question 35

what is the nature of the disease mutation in huntington’s disease?

Answer 35

The huntingtin gene (HTT) encodes for the protein huntingtin. Part of this gene contains a microsatellite, a repeated section called trinucleotide repeat, which is variable in length.
Dynamic mutations may lead to an increase in the length of the repeat.
Above a certain threshold level of repeat number, an altered form of the huntingtin protein is produced, called mutant huntingtin. This altered protein causes the pathological changed associated with the symptoms of Hingtington’s.

Question 36

what is a microsatellite?

Answer 36

Also known as a simple sequence repear (SSR) or short tandem repeat (STR), is a type of repetitive DNA sequence found throughout the genome.
Microsatellites consist of short sequences of DNA, typically ranging from 1 to 6 base pairs in length, that are repeated multiple time in a row.

Question 37

A mutation is discovered in the protein-coding region of the zebra ‘stripy’ gene: it is a substitution of a T for an A that changes the amino acid residue at position 314 of the ‘stripy’ protein from valine to phenylalanine. The mutation causes no change in phenotype, even when homozygous.

The mutation in the stripy gene is best described as:

Answer 37

A missense mutation.

A missense mutation is a point mutation (substitution of a single nucleotide base) that results in a codon change that encodes for a different amino acid.

An insertion mutation results in the introduction of at least one nucleotide base, that usually results in a reading frame shift in the gene.
A nonsense mutation results in a formation of a premature stop codon that encodes a truncated, incomplete and non-functional protein product.
A silent mutation is a type of point mutation that does not result in a change of amino acid. As this mutation does not have an effect on phenotype, it is neither dominant nor recessive.

Question 38

missense mutation

Answer 38

substitution of a single nucleotide base
> results in a codon change that encodes for a different amino acid

Question 39

insertion mutation

Answer 39

intro of at least one nucleotide base
> usually results in a reading frame shift in the gene

Question 40

nonsense mutation

Answer 40

results in formation of a premature stop codon that encodes a truncated incomplete and nonfunctional protein product

Question 41

silent mutation

Answer 41

type of point mutation that does not result in a change of amino acid.
as this mutation does not have an effect on phenotype, it is neither dominant nor recessive.

Question 42

the mother of a young family has just been diagnosed with a rare, autosomal dominant disease. She is a heterozygote and her partner is healthy. The partner and her children have not been genetically tested.

What is the most likely probability that the youngest child (of 4) will go on to develop the condition?

Answer 42

45-55%

Question 43

what is a copy number variant (CNV)?

Answer 43

differs in the number of repeats of a chromosome segment

copy number variation is a phenomenon in which sections of the genome are repeated and the number of repeats in the genome varies between individuals.
specifically, it is a type of duplication or deletion event that affects a considerable number of base pairs.
depending on how many deletion or duplication events have occurred in an individual, the number of repeated segments will vary.

Question 44

A recessive mutation is discovered in worms that extends their lifespan. The mutation occurs in the gene encoding a membrane protein that pumps calcium out of neurons.
What is the most likely explanation/hypothesis for the role of calcium in determining lifespan of worms?

Answer 44

mutation in the calcium pump gene increases worm lifespan, then it seems likely that calcium plays some role in worm lifespan.
the calcium pump is responsible for the export of calcium only, therefore, intracellular calcium is likely to be the cause of extended lifespan.

Question 45

for a bi-allelic single nucleotide polymorphism (SNP) with known allele frequencies (p and q) in the population, what does the hardy-weinberg equation predict?

Answer 45

the stable proportions of genotypes in the population if evolution is not happening.

The hardy-weinberg principle states that allele frequencies will remain constant in a population from generation to generation in the absence of other evolutionary influences.

These evolutionary influences may include genetic drift, mate choice, assortative mating, natural selection, sexual selection, mutation, gene flow, meiotic drive, genetic hitchhiking, population bottlenecks, founder effect and inbreeding.

Question 46

what does bi-allelic mean?

Answer 46

refers to a genetic locus that has two different alleles/variations of a particular gene.

Aa (bi-allelic)

allele; variant form of a gene that is located at a specific position on a chromosome. In diploid organisms (e.g. humans) each individual has two copies of each gene, one from each parent.

Question 47

9% of people have curly hair and this trait behaves as autosomal recessive. What percentage of the population does the hardy-weinberg equation predict to be the carrier (i.e. heterozygous) for this trait ?

Answer 47

p^2 + 2pq + q^2 = 1
p + q = 1

q^2=0.09

q=0.3 p=0.7

2pq = 2 x 0.3 x 0.7 = 0.42
= 42%

p^2 (AA) pq= (Aa) q^2 = (aa)

Question 48

when a population is in hardy-weinberg equilibrium for a given single, bi-allelic trait, which of the following statements is most likely to be true for that population over the next generations?

Answer 48

the hardy-weinberg principle states that allele frequencies will remain constant in a population from generation to generation in the absence of other evolutionary influences.
these evolutionary influences may include genetic drift, mate choice, assortative mating, natural selection, sexual selection, mutation, gene flow, meiotic drive, genetic hitchhiking, population bottlenecks, founder effects, and inbreeding.