Introduction to Genetics and Genomics - key concepts

Question 1

Define: gene

Answer 1

Specific stretch of DNA where the sequence contains genetic instructions

Question 2

What are a few different ways in which variation in the genome arises?

Answer 2

1) alterations in the sequence of bases in a specific section of DNA - single nucleotide polymorphism (SNPs) or small deletions or duplications (few bases)
2) Larger deletions/duplications (copy number variation) of DNA segment - include one to many genes
3) Changes in the number or structure of chromosomes

SNPs are the most common mutations

Question 3

What is the difference between chromosomal rearrangements and single base changes?

Answer 3

Chromosomal rearrangements are large

Single base changes are small

Question 4

What is the difference between single nucleotide polymorphisms in population and mutations in a gene in one family?

Answer 4

SNPs in population = common

Mutation in a gene in one family = rare

Question 5

What is the difference between non-harmful polymorphisms and variations that disrupt gene function

Answer 5

Non-harmful polymorphisms are non-pathogenic, whereas when gene function is disrupted they are pathogenic

Question 6

When are polymorphisms not harmful?

Answer 6

occur in non-functional DNA
occur within gene but does not change amino acid
changes the amino acid but not the protein function

Question 7

What is a defining factor in being a SNP?

Answer 7

a base changes has to have a frequency of >1%

Question 8

What is PCR?

Answer 8

PCR takes advantage of the ability of nucleic acids to hybridise
Its a medical research and diagnostic tool
- take template DNA and add nucleotides and this reaction links nucleotides together to amplify the amount of DNA to enable you to carry out experiments

Question 9

What is microarray analysis?

Answer 9

tells you which genes are turned on in different cells

• base level
• large blocks of DNA

Question 10

What is karotyping?

Answer 10

using light microscopy you can look for differences between chromosomes to check for crossover for example

Question 11

When do mutations occur and what causes them?

Answer 11

Cell division

Intrinsic and extrinsic attacks on DNA

Question 12

What can be seen in interphase?

Answer 12

nuclear envelope intact

No chromosomes visible

Question 13

What can be seen in prophase?

Answer 13

Chromosomes condense and become visible

Bipolar spindle develops

Question 14

What can be seen in prometaphase?

Answer 14

Nuclear envelope dissolves

Chromosomes begin to migrate to equatorial plane and are seen to contain 2 chromatids

Question 15

What can be seen in metaphase?

Answer 15

Chromosomes fully condensed and located at metaphase plate

Tension on kinetochores at centromeres facing opposite directions

Question 16

What can be seen in anaphase?

Answer 16

Each centromere splits

The two chromatids of each chromosome are pulled to opposite poles

Question 17

What can be seen in telophase?

Answer 17

Chromosomes reach poles and start to decondense
Nuclear membrane reforms
Cytoplasm starts to divide

Question 18

What can be seen in cytokinesis?

Answer 18

Cytoplasm division completed to give two daughter cells

Question 19

What questions need be considered at the different checkpoints of the cell division process?

Answer 19

Checkpoint in mitosis:
- Are all chromosomes properly attached to the mitotic spindle
G1 Checkpoint:
- Is the environment favourable
G2 checkpoint:
- Is all the DNA replicated?
- Is all DNA damage repaired?

Question 20

How could errors in DNA replication and mitotic cell division cause human disease?

Answer 20

DNA replication: new mutations =copying errors

Chromosome segregation at mitotic cell division: anomalies of chromosome number = non-dysjunction

Question 21

What is mosaicism?

Answer 21

some cells are affected by chromosomal anomalies while other cells are normal

Question 22

What are the functions of meiosis?

Answer 22

Reduction division (23 chromosomes per gamete)
Reassortment of genes
Independent segregation of chromosomes crossing over

Question 23

What is the mechanism of meiosis?

Answer 23

Each homologue replicates to give two chromatids -homologues pair
Exchange of material between non-sister chromatids - crossing over/recombination
Chiasmata (visible cytologically) are physical manifestations of crossing over - 2 chromosomes are linked to one another

Question 24

How many potential different combinations are there after independent assortment of maternal and paternal homologues after meiosis 1?

Answer 24

8.4 million different combinations

Question 25

What are the differences between gametogenesis in females and males?

Answer 25

In females you end up with one egg and in males you end up with 4 mature spermatozoa

Question 26

How many cells divisions and how many oocytes have been produced by 5 months gestation in a female?

Answer 26

22 cell divisions producing a stock of 2,600,000 oocytes

Question 27

What does deletion/insertion and substitution mutations cause?

Answer 27

cause gain of function or loss of function

Question 28

What are silent mutations/sequence variant mutations?

Answer 28

A base pair change that does not change the amino acid sequence

Question 29

What are missense mutations?

Answer 29

Missense: changes to a codon for another amino acid (can be harmful mutation or neutral polymorphism)

Question 30

What is a non-sense mutation?

Answer 30

Non-sense:change from an amino acid codon to a stop codon

Question 31

What is a splice site mutation?

Answer 31

Splice site mutation: a change that results in altered RNA sequence

Question 32

What is a frameshift mutation?

Answer 32

Frameshift: insertion or deletion of base pairs, producing a stop codon downstream

Question 33

Why can a mutation within an exon have no phenotypic effect?

Answer 33

may have no phenotypic effect if there is no change in the amino acid - genetic code is degenerate

Question 34

What are the predicted effects of hydrophilic and hydrophobic amino acids?

Answer 34

Hydrophilic- soluble, not in hydrophobic environment e.g. not in lipid membrane

Hydrophobic - anchor protein to a membrane, with hydrophilic central part of cytoplasm

Question 35

What happens after a mutagenic hit to the DNA of a cell?

Answer 35

DNA damage either causes activation of DNA repair systems or stops cell division
- the DNA repair systems ay be successful and fix the mutation or they may be unsuccessful and lead to replication of the mutation causing it to be transmitted to daughter cells

Question 36

What can variations/mutations involve?

Answer 36

• single gene (mendelian inheritance)
• chromosomal segment (whole chromosome) and so affect thousands of genes (copy number variant)
• several variants of genes acting with environmental influences (multifactorial inheritance)

Question 37

What is the phenotype dependent upon and what affects them?

Answer 37

Dependent upon patterns of gene expression which are affected by:

• regulation of transcription of individual genes
• differential splicing of transcripts
• Multiple genes acting together in developmental pathways

Question 38

What do transcription factors do?

Answer 38

Recognise small DNA sequences in the promoter and enhancer regions of a gene

• either activate or repress expression of mRNA
• several may act in collaboration
• genes that give rise to proteins define a particular cell type maybe regulated by the same transcription factors

Question 39

What are pathways controlling the development of the human foetus often sensitive to?

Answer 39

dosage of the gene products in the pathway