Basic Genetics Flashcards
Define Evolution
Evolution means change in the form and/or behaviour of organisms between generations
What is an allele?
A variant of a genetic character at a given locus on a chromosome
What is a gene?
A unit of heredity, carrying information for a single polypeptide of RNA
What is a gamete?
A mature sexual reproductive cell (the egg or sperm)
Briefly describe Mendel’s Law of Segregation
- Somatic cells of a diploid organism contain 2 sets of chromosomes
- Chromosomes in the reproductive cells segregate during meiosis
- Produced gametes contain only one set of chromosomes, fusing of the two gametes results in a diploid zygote
- The F1s produce two types of gametes
What equation would we use to answer the following question:
” What is the probability (P) of F2s inheriting two “S” or “s” alleles?”
Probability (P) = (number of times something happens) / (number of times it could happen)
What does the phenotypic ratio 3:1 (or 1:2:1) indicate?
It indicates a monogenic nature of the phenotype
Briefly describe Mendel’s 2nd Law (Independent Assortment)
- Alleles of different genes assort independently
What is meant by the term “diploid”?
Refers to 2 copies of heritable units
What is meant by the term “haploid”?
Refers to 1 copy of heritable unit
What does “heterozygous” mean?
An individual with two different alleles of heritable unit (gene)
What does “homozygous” mean?
An individual with two of the same alleles of heritable unit (gene)
What does “hemizygous” mean?
An individual with one allele of heritable unit (gene)
- Males are hemizygous for the X chromosome genes
Briefly describe recombinant phenotypes
- Phenotypic combinations are not present in parents of F1s; they appear in the F2s
- There is a bias towards the parental phenotype
- Recombinant phenotypes appear because alleles of the two genes assort independently (providing the genes are not linked) during meiosis
What is “Linkage”?
Genes on the same chromosomes are linked.
- Closely linked genes DO NOT obey Mendel’s 2nd law & DO NOT assort independently
- This characteristic can be used to determine location of genes in the genome and their “order” on the chromosome
- Linkage also helps to understand the phenotypic resemblance between close relatives
Briefly describe how “crossing-over” and “recombination” are linked
- During meiosis, homologous chromosomes pair up
- At this time, crossing-over can occur between chromatids of different homologs
- This creates 2 “recombinant” chromatids with genetic material from different homologs
- The closer linked two genes are, the less likely the recombination will occur between them.
How can we calculate the recombination frequency?
Recombination frequency (RF) = Number of recombinants (R) / (Number of recombinants + Parental type (P))
RF = R/(R+P)
What is a genetic map?
A genetic map shows the position and order of genes along each chromosome and can help in understanding the function of the genes
What are the two main meanings of the term “haplotype”?
- A group of genes inherited together from a single; two linked genes, within 2 existing alleles each, give 4 haplotypes
- Can also refer to the inheritance of a cluster of Single Nucleotide Polymorphisms (SNPs); Haplotype is made up of a particular combination of alleles at nearby SNPs
What controls skin/coat colour in mammals?
Melanocytes
Briefly describe melanin synthesis
- Tyrosynase (Tyr) catalyses several reactions converting tyrosine to precursors of melanin
- Inactivation of Tyr due to mutation precludes production of melanin precursors; if homozygous, it results in albino phenotype
- Tyrosynase related protein 1 (Typ1), encoded by Trp gene, participates in coversin of a lighter to darker eumelanin.
- Homozygous carriers of mutant Trp11 turn brown.
- The gene is relevant across various mammalian species - Trp1 mutation is underlying cause of melanesian blonde hair in humans
The Himalayan allele (C^h) is heat-sensitive. What does this mean?
No melanin is present in warmer areas of the body
What is the result of no melanocytes being present in certain areas?
Piebald patterning (spots)
Briefly describe the agouti allele
Wild type, produces agouti phenotype by introducing a band of yellow colour resulting from deposition of phaeomelanin (yellow pigment) on the dark shaft of hair
Briefly describe incomplete dominance
- Many alleles are not completely dominant or recessive; their effects blend together or mix such alleles often referred to as ADDITIVE alleles
- Examples include the colours of snap-dragon flowers (red//pink//white)
- The inheritance still follows Mendel’s laws
Briefly describe co-dominance
Co-dominant alleles are ones whose effects can both be seen together in the phenotype
- A good example is the human ABO blood group system
- This has 3 alleles, I^A, I^B, I^O; their presence in a person’s blood can be detected using specific antibodies
What is epistasis?
Phenotypic expression of one gene can be conditional on the allele of another gene.
Describe Siamese cats as an example of gene-environment interaction
- Pigments produced because enzymes are active in cooler parts of the body
- If you were to remove some dark fur and then keep the cat in a warm environment, the fur would grow back lighter
- The proportion of individuals carrying the allele that actually show the phenotype is called the PENETRANCE
What is pedigree analysis?
When monogenic traits are followed in families
Briefly describe autosomal dominant inheritance
- Every affected individual has an affected parent
- ~50% of the offspring are affected
- Both sexes affected
Briefly describe autosomal recessive inheritance
- Both parents not affected
- ~25% of the offspring affected
- Phenotype occurs in both sexes
When did sexual reproduction first appear?
~1.2 billion years ago
What are the advantages of sexual reproduction?
- Genetic diversity due to recombinations
- Complementation or hybrid vigor
What does “monoecious” mean?
An individual that can produce both male and female gametes
What does “dioecious” mean?
Individuals are either male or female
Briefly describe sex determination in bees; state whether they are monoeicious or dioecious
- Dioecious
- Unfertilised haploid eggs produce males (drones)
- Fertilised haploid eggs produce females (workers, queen)
- Same in ants and many other invertebrates
- Halplodiploid sex determination
Briefly describe reproduction in grasshoppers; state whether they are monoeicious or dioecious
- Dioecious
- All diploid, males have one X chromosome & females have two X chromsomes
- XO sex determination
Briefly describe reproduction in humans & fruit flies; state whether they are monoeicious or dioecious
- Dioecious
- Haploid sperm, contain a X or a Y chromosome; eggs contain a X chromosome
- Females are XX
- Males are XY
- XY sex determination
Briefly describe sex determination in birds & butterflies
- Males are ZZ
- Females are ZW
- ZW sex determination
What are the different sex determination systems in dioecious organisms?
- Haplodiploid
- XO
- XY
- ZW
Describe reproduction in bees
- Bees do not have sex chromosomes
- To be female, the bee has to be heterozygous for complementary sex determiner (CSD) gene
- CSD has 19 different alleles so a diploid bee is likely to be heterozygous
- Rare homozygous diploid bees develop into sterile males and are killed by workers
- Intensive selection by bee-keepers can reduce genetic diversity and increase chances of CSD homozygosity
What is the CSD gene?
Complementary sex determiner
SRY is a located on the Y chromosome & DAX1 is located on the X chromosome. How do these interact with each other in terms of sex determination?
DAX1 protein prevents the development of testis and allows the development of ovaries;
SRY protein overcomes the effect DAX1 and allows testis to develop
- Primary sexual characteristics
What are secondary sexual characteristics controlled by?
Hormones, not by X & Y directly.
Briefly describe sex determination in Drosophila
- Sex is determined by the ratio of the number of X-chromosomes relative to the autosomes
- The key genes are 4 transcription factors; sis-a; sis-b; sis-c & run, a.k.a “X-linked numerator” genes (all on the X chromosome) & dpn, autosomal “denominator” gene (2R)
- Ratio of these genes determines whether individual develops male or female
- XO is a sterile male
- XXY is a fertile female
Briefly describe sex-linked inheritance
- There are very few genes on the Y chromosome but, lots on the X chromosome. Their inheritance show sex-linkage in pedigrees
- The outcome of a cross depends on which parental genotype is from the father and which from the mother
- The reciprocal crosses do NOT produce the same results
What is the cause of haemophilia?
A hereditary disorder caused by a defective gene on the X-chromosome
From which parent do we inherit mitochondrial DNA?
Mother (maternal inheritance)
Why are bacteria good model systems for mutation?
Bacteria are: unicellular; they have a single, haploid chromosome; they replicate by binary fission* & simple gene structure
*Meaning the daughter cells are identical to parent; clonal & no genetic variation from growth cycle
What is a “mutant”?
An altered organism
What is a “mutation”?
An altered genome
What is “mutagenesis”?
The process of alteration
Briefly describe mutants in bacteria
Mutations can affect bacteria in a number of ways:
- Inability to use a substrate (i.e. sugar)
- Making them auxotroph; needing another amino acid or vitamin to survive
- Resistance; to antibiotics; phage or toxic chemicals
How do we select and detect mutants?
In:
- Non-selective media; all cells grow so we test individual clones (replica plating)
- Selective media; antibiotic present; absence of amino acid
- Indicator media; MacConkey agar (Lac^+/-)
How do we look at mutants in higher organisms?
In:
- Appearance; i.e. colour, shape or size
- Behaviour; inborn errors of metabolism
What are different types of point mutations?
- Nucleotide substitutions (SNPs)
- Frameshift mutations
What are the different types of “Larger-Scale” mutations?
- Deletions; removes gene(s); may change phenotype
- Insertions; adds gene(s); may change phenotype
- Rearrangements; re-orders gene(s); may not change phenotype
What is a “forward mutation”?
Wild type phenotype –> mutant phenotype
Wild type sequence –> mutant sequence
What is a “reversion”?
Mutant phenotype –> Wild type phenotype
Reverse (back) mutation:
Mutant sequence –> Wild type sequence
Suppressor mutation:
Mutant sequence –> More mutations elsewhere
What equation do we use to measure mutation rate?
Ratio = (number of mutants/number of wild types)
What do we use mutation rates for?
- Population genetics
- Evolutionary studies
- Measuring effects of mutagens
What is a “transition mutation”?
- Purine Purine
- Pyrimidine Pyrimidine
What is a “transversion mutation”?
- Purine Pyrimidine
Briefly describe spontaneous mutations
- Mutation is a random event
- Mutations occur independently of a selective (dis)advantage to host
- Each GENE mutates at a characteristic rate; probability of mutation in a particular gene
- Each TYPE of mutation occurs at a characteristic rate
What are “base analogues”?
- Molecule similar to one of the 4 DNA bases; can ONLY be incorporated into DNA at replication; can pair with a normal base
- Analogue occasionally mis-pairs with other bases; nucleotide change (mutation) will then occur during DNA replication
5-bromouracil is a base analogue. Describe.
- Analogue of thymine so pairs with adenine
- Conformational change of a 5-BU leads to pairing with guanine
Briefly describe DNA modifying chemicals
- React with normal DNA bases to change their base pairing
- Active on replicating AND non-replicating DNA
- Different agents are more or less specific in their alternations; NITROUS ACID: A-T –> G-C transitions; ALKYLATING AGENTS: A-T G-C transitions
Briefly describe intercalating chemicals
- Planar, ringed molecules the size of a base pair: e.g. acridine, ethidium bromide
- Intercalate into dsDNA between base pairs
- At DNA replication, get nucleotide added (or deleted) in daughter strand
- Frameshift mutations in coding sequence
Briefly describe the effect of ultraviolet radiation on DNA
- UV energy absorbed by base
- Chemical modification of base
- Adjacent pyrimidines covalently bond; Pyrimidine dimers
- DNA helix distorted; Replication & transcription blocked
Briefly describe the effect of ionising radiation on DNA
4 types
- Free radicals formed
- React with & damage DNA: nucleotide substitutions (easy to repair); ssDNA breaks (easy to repair); dsDNA breaks (hard to repair)
- Dose mutation rate
Why are bacteria particularly prone to DNA damage?
- Haploid; all mutations dominant
- Unicellular; whole organism affected
When is DNA repair most effective?
Repair most effective before replication
Briefly describe apurinic gap repair
- Most common spontaneous degradation of DNA; hydrolysis of sugar-purine bond–> loss of purine
- Repair by AP endonuclease; removes damaged base, ss gap filled by polymerase
- If no repair, adenine is inserted at replication
Briefly describe mismatch repair
- Mismatch repair gene: mut
- Mismatched base pair detected
- Nearby ss cut & excision of ssDNA past mismatch; Daughter strand preferably excised
- DNA polymerase repairs gaps
Briefly describe photoreactivation repair
- Various enzymes with specific properties
e. g.
- Cleavage of pyrimidine dimers (T^T)
- Enzyme binds to dimer
- Energy of blue light cleaves bond
Briefly describe excision repair
- Multi-enzyme system
- Repairs stretch of damaged nucleotides; damaged ssDNA excised; gap repair by polymerase
Briefly describe post-replication repair
- Polymerase can’t replicate across damaged nucleotides; it leaves gaps
- Gap filled by strand exchange from the other dsDNA
- Secondary gap repaired by polymerase
