Transmission Genetics Flashcards
What are the 3 basic types of mutation?
- Point Mutations/Base substitution where the DNA length doesn’t change
- insertions where DNA gets longer
- deletions here DNA gets shorter
what does indel mean?
cant distinguish whether the mutation was an insertion or deletion of bases either way frameshift is changed
What are the two types of substitution mutations?
Transition - subs of purine for purine or pyrimidine for pyrimidine
Transversions - subs of purine for pyrimidine or vice versa
Which is the most common substitution mutation ?
Transitions but more possible kinds of transversions than transitions
What is the diff between somatic cell mutations and germline mutations ?
Somatic in body cells cause cancer and aging
Germ line in gametes only and are passed onto the next generation
How does a ‘wobble’ cause a point mutation?
1) dna strand separates for replication
2) thymine on original template strand pairs with guanine leading to error
3) next round of replication , G pairs with c causing a transition mutation
What does depurination and deamination mean?
Depurination - loss of purine via hydrolysis which produces an APURINIC SITE which A usually fills.
Deamination - loss of amino acid group, common when C is methylated, VERY PREVALENT
What does DNA oxidisation cause?
Oxygen free radicals damage dna. Changing guanine into 8-puc-7,8-dihydrodeoxyguanine
Briefly explain chemically induced UV radiation mutation
Pyrimidine dimer causes them not to be replicated properly and two Thymine bases block replication.
Briefly explain SOS system in bacteria
allows cells to bypass replication block with a mutation prone pathway
What occurs in strand slippage?
- a newly synthesised strand loops out causing addition of one nucleotide on new strand.
- a template strand loops out resulting in omission of one nucleotide on new strand
What does unequal crossing over cause regards to mutation?
Homologous chromosomes misalign during crossing over so one crossover products contains insertion and other deletion
What is a repeat expansion?
A special case of insertion where an increase to the number of copies of codons of nucleotides occurs.
Can lead to fragile X mutation.
What is the mechanism for repeat expansion?
Not fully understood but thought to be a hair pin forms in replication and pairs on itself
Explain male mutation bias
- females have set no. Of replications for eggs
- men have ongoing replications for sperm so mutation more likely
- most new mutations originate in males
- autism and schizophrenia more common in kids with older fathers
What and when does chromosomal deletion occur?
- In heterozygous for a deletion the normal chromosome loops out during chromosome pairing in prophase I.
- caused by unequal crossing over
- result in chromosomal loops
What is a chromosomal inversion and what are the two types?
- Seg of chromosome turned 180 degrees
Paracentric - centromere unaffected
Pericentric - centromere affected, recombinant gametes have chromosomes of normal size but too many or few of some genes
What are the fitness affects of inversions?
- gene splits in middle, same DNA diff order
- disrupted meiosis
- affected gene expression
What is an example of position effect variegation?
- inversion moves white + gene near heterochromatin
- when het white + silenced —> white facets. When expressed respect facets.
Definition of translocation
Movement of genetic info between non homologous chromosomes.
3 types of translocation
Non reciprocal - movement is uni directional
Reciprocal - two detached fragments of two diff chromosomes are switched
Robertsonian Translocation - short arm of one Acrocentric chromosome is exchanged with long arm of other. Common in house mice.
How can translocation be deleterious?
- cut in middle of genes
- change gene expression
- associated with loss of genes
What are the 4 types of aneuploidy?
Nullisomy - loss of both members of homologous pair of chromosome
Monosomy - loss of single chromosome
Trisomy - gain of single chromosome
Tetrasomy - gain of two homologous chromosomes
What are the causes of aneuploidy?
- deletion of centromere during meiosis
- Robertsonian translocation
- non disjunction during meiosis and mitosis
What is non disjunction?
Improper segregation of chromosomes
- can occur in meiosis and mitosis
What is primary Down syndrome?
- 95% of DS patients
- 91% non disjunction in maternal meiosis
- 7% paternal
- older mother more likely to give birth to child with ds
What are the causes of maternal age affect?
Reduced cohesion - is sister chromatids not attached at prophase no cross over occurs and cross over necessary for segregation.
- must be pried in metaphase plate to ensure 1 to each pole
What is familial Down syndrome?
- translocation of chromosome 21 onto another
- long arm of 21 attached to 14
- people can be carriers
- higher rates of miscarriage
What is polyploidy?
Presence of more than two sets of chromosomes
- common in plants rarer in animals
- many crops polyploidy - increased size
- African clawed frogs
What are the two types of polyploidy?
Autopolyploidy - all chromosomes from single species
- can arise through non disjunction in meiosis.
- failure of cytokinesis leads to autotetraploids
Allopolyploidy - from 2 species
- arise from hybridisation followed by chromosome doubling
What is an autotriploid?
- cell with two or more copies of a single haploid set
- some haploid gametes could occur
Usually sterile.
Bananas
Brief overview of Mendel and his experiments
- experiments 1856-1863. Discovering principles of heredity in 1866.
- focused on discontinuous traits.
3 laws of inheritance
1) Laws of segregation
2) law of independent assortment
3) principle of dominance
Why is a pea important as a study organism?
- easy to cultivate
- many progeny
- 1 growing season
- many pure breeding varieties
What was Edith Rebecca Saunders’s role?
Rediscovery of Mendels work
What are the problems with Mendels work?
- why didn’t he find linkage?
- did he even do the experiments?
- values too close to 3:1 ratios
What is a mono hybrid cross and what conclusions can be drawn from it?
- cross between 2 parents that differ in a single characteristic
4 conclusions:
- 1 character encoded by 2 genetic factors (alleles)
- 2 alleles separate when gametes formed
- concept of dominance
- 2 alleles separate with equal probability into gametes.
Mendels method for monohybrid cross
1) took pea plants that were true breeding
2) peas usually self fertilising so removed anthers to prevent this
3) force bred plants or 7 diff traits.
F1 cross - homozygous round X homozygous wrinkled
F2 cross - let products of F1 self fertilise
3:1 ratio
What conclusions could be drawn from monohybrid cross?
- inheritance is not blending
- inheritance is particulate
- F1 still has info for both phenotypes because seen in F2
- alleles segregate 50:50
- law of seg and principle of dominance discovered from crosses
How would you test for Mendelian ratios?
- chi squared
- degrees of freedom = number of phenotypes - 1
- if answer less than DOF then not significant difference from expected ratio
What are the problems with inbreeding?
Accumulation of recessive alleles
How cystic fibrosis was caused.
What are dihybrid, crosses what do they reveal?
- revealed independent assortment and linkage
- more than one locus considered at same time
eg round yellow and wrinkled green
9:3:3:1 ratio of F2 gen.
Linked vs unlinked in dihybrid crosses
- if genes completely linked then no crossing over so progeny are non recombinant
- unlinked then 1/2 progeny are recombinant
How to estimate cross over rate between loci
No. Of recomb progeny / total number of progeny x 100
What is Non Mendelian inheritance?
- when we don’t see a 50:50 ratio for inheritance of genes.
- many genes maternally inherited eg mitochondrial and chloroplast
Two types of Non Mendelian inheritance
Cytoplasmic - uniparental inheritance of mitochondria and chloroplasts
Nuclear - gene conversion, homing endonucleases, B chromosomes, meitoic drive.
Features of mitochondrial DNA
- genomes are small
- many genes
- no introns almost all DNA coding
myopathy is an example of a mitochondrial DNA disease
What is Homoplasmy and Heteroplasmy?
Homo - all organelles are genetically identical
Hetero - multiple distinct DNA sequences with cytoplasm of single cell
What is replicative segregation?
- organelles in heteroplamic cell divide randomly into progeny
- mitosis daughter cells of organelles not identical to parent due to stochastic sampling
- you get homo from hetero parents
What is variegation?
- diff coloured parts of plants due to heteroplasmy
What are cytoplasmically inherited traits?
Usually inherited from one parent usually maternal.
What is Gene conversion?
- normally get 50:50 but can also get 3:1 or 5:3
- can occur in meiosis when two chromosomes start down the road doing crossing over but resolve process differently
- ALWAYS CAUSES DEATH OF GAMETES
What are homing endonuclease genes?
- stretches of DNA that code for sequences that both copy itself and cut the occupied allele at the correct insertion site
- if in Germline of heterozygotes then more gametes with HEG
What are B chromosomes?
- extra chromosomes
- not essential for survival of species
5% of humans have - not transmitted in humans
What is meitoic drive?
- gametes produced have unequal chance to fertilise
- chromosomal level distortion
- death of half of gametes
Defy’s Mendels law
Sk wtf is meitoic drive gene, alternatively spliced.
Short transcript - poison long - antidote. Leaves cell and affects other gametes.
What are two types of separate sexes which one can be?
Monoecious - individual has both male and female reproductive structures
Dioecious - individual has either male or female reproductive system
In sperm 1/2 small chromosomes 1/2 large
In egg all same
What is heterogametic sex and homogametic sex?
Hetero- produces gametes with diff types of sex chromosome
Homo- gametes all contain same sex chromosome
What is haplo - diploidy?
- if all autosomes to X and No Y
- unfertilised haploid eggs —> male
- fertilised diploid zygotes —> female
- full sisters identical
What is parthenogenesis?
Development of eggs without fertilisation
What is genic sex determination?
Sex determination gene but no sex chromosomes ( yeast have a and alpha)
Examples of environmental sex determination
- TSD - temp dependent sex determination
- clown fish all male dominant go to female
- called sequential hermaphroditism
Eg. Crepidula Fornicata
What is the XY mechanism variable?
- if XXY then same ratio of X to autosomes so female
- SRY gene on Y chromosome determines maleness
- absence of Y —> female
What is androgen insensitivity syndrome?
- females have XY and testosterone can’t reproduce.
Example of Sex linked traits
Cock feathering only in hh male
X linked trait example
White eyes flies and red green colour blindness
What does X inactivation lead to?
- mosaicism
- in every cell one X is inactivated
5 classified mutations
FORWARD - wild type —> mutation REVERSE - mutation —> wild type Missense - amino acid —> diff amino acid Non missense - sense codon —> stop codon Silent - codon —> synonymous codon
Mutations classified by phenotypic effect
Loss of function mutations - common
Gain of function - uncommon
Conditional - effect of mutation depends on something else
Suppressor mutations - mutation hides of suppressed effects of previous mutation
(Intra Or intergenic)
What is an intragenic suppressor mutation?
Occurs in gene containing the mutation being suppressed
1) mutation occurs in gene
2) second mutation in diff site in same gene
3) restores original amino acid
What is in intergenic suppressor mutation?
1) wild type sequence produces full length functional protein
2) base substitution in site in gene produces stop codon resulting in shortened functional protein.
3) base subsitiution at other site in other gene codes tRNA alters anticodon of tRNA Tyr, this pairs with stop codon in original mutation
Types of duplications which can occur
Most happen on same chromosome
1) intra which is next to each other as opposed to displaced which isn’t. TANDEM is next to each other.
2) reverse where section repeated but flipped
3) duplicated chromosomes loop out during prophase I
What are segmental duplications?
- More than 1000 bp. (<=Indel)
- 4% of human genomes is this
- can lead to deletions and unequal crossing over
Fruit fly sex alleles AA XXX individual is a…
metafemale
At the end of eukaryotic chromosomes there are…
Telomeres
What is Deamination of methylcytosine causes
C to go to T
What does gene conversion always cause?
always causes the death of gametes
What does unequal crossing over cause?
generates a duplication and deletion
Fragile X syndrome is an example of…
a disease commonly caused by trinucleotide repeat expansion
On discovering a new mammal we number the chromosomes in size order (chromosome 1 being largest) we have found out that…
Trisomics for chromosome 1 will be the rarest
