Introduction to Genetics and Genomics - key concepts Flashcards
Define: gene
Specific stretch of DNA where the sequence contains genetic instructions
What are a few different ways in which variation in the genome arises?
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
What is the difference between chromosomal rearrangements and single base changes?
Chromosomal rearrangements are large
Single base changes are small
What is the difference between single nucleotide polymorphisms in population and mutations in a gene in one family?
SNPs in population = common
Mutation in a gene in one family = rare
What is the difference between non-harmful polymorphisms and variations that disrupt gene function
Non-harmful polymorphisms are non-pathogenic, whereas when gene function is disrupted they are pathogenic
When are polymorphisms not harmful?
occur in non-functional DNA
occur within gene but does not change amino acid
changes the amino acid but not the protein function
What is a defining factor in being a SNP?
a base changes has to have a frequency of >1%
What is PCR?
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
What is microarray analysis?
tells you which genes are turned on in different cells
- base level
- large blocks of DNA
What is karotyping?
using light microscopy you can look for differences between chromosomes to check for crossover for example
When do mutations occur and what causes them?
Cell division
Intrinsic and extrinsic attacks on DNA
What can be seen in interphase?
nuclear envelope intact
No chromosomes visible
What can be seen in prophase?
Chromosomes condense and become visible
Bipolar spindle develops
What can be seen in prometaphase?
Nuclear envelope dissolves
Chromosomes begin to migrate to equatorial plane and are seen to contain 2 chromatids
What can be seen in metaphase?
Chromosomes fully condensed and located at metaphase plate
Tension on kinetochores at centromeres facing opposite directions
What can be seen in anaphase?
Each centromere splits
The two chromatids of each chromosome are pulled to opposite poles
What can be seen in telophase?
Chromosomes reach poles and start to decondense
Nuclear membrane reforms
Cytoplasm starts to divide
What can be seen in cytokinesis?
Cytoplasm division completed to give two daughter cells
What questions need be considered at the different checkpoints of the cell division process?
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?
How could errors in DNA replication and mitotic cell division cause human disease?
DNA replication: new mutations =copying errors
Chromosome segregation at mitotic cell division: anomalies of chromosome number = non-dysjunction
What is mosaicism?
some cells are affected by chromosomal anomalies while other cells are normal
What are the functions of meiosis?
Reduction division (23 chromosomes per gamete)
Reassortment of genes
Independent segregation of chromosomes crossing over
What is the mechanism of meiosis?
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
How many potential different combinations are there after independent assortment of maternal and paternal homologues after meiosis 1?
8.4 million different combinations
What are the differences between gametogenesis in females and males?
In females you end up with one egg and in males you end up with 4 mature spermatozoa
How many cells divisions and how many oocytes have been produced by 5 months gestation in a female?
22 cell divisions producing a stock of 2,600,000 oocytes
What does deletion/insertion and substitution mutations cause?
cause gain of function or loss of function
What are silent mutations/sequence variant mutations?
A base pair change that does not change the amino acid sequence
What are missense mutations?
Missense: changes to a codon for another amino acid (can be harmful mutation or neutral polymorphism)
What is a non-sense mutation?
Non-sense:change from an amino acid codon to a stop codon
What is a splice site mutation?
Splice site mutation: a change that results in altered RNA sequence
What is a frameshift mutation?
Frameshift: insertion or deletion of base pairs, producing a stop codon downstream
Why can a mutation within an exon have no phenotypic effect?
may have no phenotypic effect if there is no change in the amino acid - genetic code is degenerate
What are the predicted effects of hydrophilic and hydrophobic amino acids?
Hydrophilic- soluble, not in hydrophobic environment e.g. not in lipid membrane
Hydrophobic - anchor protein to a membrane, with hydrophilic central part of cytoplasm
What happens after a mutagenic hit to the DNA of a cell?
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
What can variations/mutations involve?
- 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)
What is the phenotype dependent upon and what affects them?
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
What do transcription factors do?
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
What are pathways controlling the development of the human foetus often sensitive to?
dosage of the gene products in the pathway
