Week 2 Flashcards
List 5 types of chromosome mutations?
Aneuploidy (number) Duplications (structure) Deletions (structure) Translocations (structure) Inversions (structure)
What causes a DNA mutation to occur?
Unrepaired damage to DNA caused by radiation or chemical mutagens
Errors in replication or recombination
Insertion or deletion of segments of DNA by mobile genetic elements
Explain meiosis in the context of aneuploidy
Meiosis involves doubling up of genetic information. “Cross over” of genetic material between maternal and paternal chromosomes of the same type. And then the division of genetic material into haploid cells containing half genetic information of a diploid cell and a mix of maternal and paternal DNA.
During meiosis there can be a malfunction in splitting of genetic material, instead of a haploid cell having one copy of the chromosome it can have 0 or 2
Give an example aneuploidy
Down’s syndrome (3 copies of chromosome 21, characterised by low iq, folds over the eye, short and broad hands and below average height)
Or Klinfelters syndrome (gain of an extra X chromosome, characterised by underdeveloped testes, some breasts, taller than average, low iq)
Or Turners syndrome (loss of an X chromosome in females)
Discuss structural mutations (duplications, deletions, translocation and aversions)
Overview
All begin with one of more breaks in the chromosome
Whe nether the break occurs, broken ends remain exposed and vulnerable to degradation
Broken ends of a chromosome are “sticky” and can adhere to other broken chromosome ends.
Or information can be deleted
Explain chromosome deletion (segment)
It’s deletion of a segment of chromosome
Deletion covering centromere (the spindle fiber which the chromosome is attached to during cell division) leads to loss of a chromosome during meiosis - non-viable offspring
I
Cri-du-chat syndrome: 5p deletion. Prader-Willi syndrome: 15q deletion
How does chromosome duplications occur and what is a syndrome that is the result of this?
Doubling of a segment of DNA caused by unequal crossing over
Important role in evolution of multiple genes with related functions
Pallister killian syndrome: 12p duplication
Explain chromosome inversions
Segment of a chromosome is cut and then reintegrated in an orientation of 180 degrees from the original orientation
Genetic material is not lost but may be phenotypic consequences when the break points occur within genesis
Explain chromosome translocation a
Change in position of chromosome segments to a different location in the genome
Rearrangement of parts between nonhomologous chromosomes (e.g. Part of chr. 17 moves to chr. 20)
Typically affects the gametesi
A lot of illnesses are linked with translocation a including schizophrenia
What is a point mutation?
Single base pair substitution
What are the two types of point mutation?
Transition mutation ( AT and GC becomes TA and CG) -common
Transversion (AT and TA becomes GC and CG)
There are four effects of point mutations what are they?
Missense
Nonsense
Neutral
Silent
What is a frameshift mutation?
(Insertions add one or more nucleotide to the DNA - deletions remove one of more nucleotide from the DNA)
If the number of nucleotides inserted or deleted is not divisible by 3 this can cause a frameshift mutation
Normally results in a non-functioning protein
Incorrect amino acids added to the polypeptide chain after the mutation site
Can generate new stop codons = shortened polypeptide
Or read through of the normal stop codon = lengthened polypeptide
What is the one gene one polypeptide hypothesis and what is an example of this?
A single gene mutation that alters the function of an enzyme
Phenylketonuria (PKU)
Discuss PKU
Recessive mutation in gene for phenylalanine hydroxylase (what breaks down phenylalanine)
PKU has pleiotropic effects as its phenylalanin affects the gene for tyrosine and tyrosine effects levels of dopa and therefore the amount of melanin produced.
Screening for PKU is done with bacterial inhibitions assay (Guthrie test)
What is an example of a mongenic disease?
Sickle-cell anaemia
Or
Cystic fibrosis
What is sickle cell anaemia?
It’s a mutation in the chemical structure of haemoglobin
What are three types of common DNA variation?
SNP: single nucleotide polymorphism
VNTR: variable number tandem repeat
CNV: copy number variants (1000bp+)
SNPs can result in three types of change, what are these?
Synonymous (doesn’t result in amino acid change)
Non-synonymous (results in amino acid chance
Non-sense (results in stop codon)
VNTPs are subcategorised into 2 families, what are these and how are that defined?
Microsatellite (2-10bp)
Minisatellite (10-60bp)
What type of DNA variation is often used in forensics and DNA fingerprinting?
Short nucleotide sequence of tandem repeats (VNTRs)
What are CNVs?
Copy number variants = duplications or deletions between 1kb - 5MB
- major cause of structural variation in the genome and account for more between-individual variation than any other form of mutation
Important in terms of evolution as CNVs account got more differences between humans and other organisms than other mutations
They are also a significant contribution to differences in gene expression between individuals.
Why are some disease alleles more common than others?
Sequence variants that are directly and overtly cause human diseases are generally rare in the population because they reduce fitness.
However a rare disease allele in one population can become a polymorphism in another if it confers an advantage and therefore increases in frequency
Example: sickle cell anaemia, in Caucasian population is rare and causes a severely debilitating blood disorder, in certain parts of Africa however the same allele is
Polymorphic because it confers resistance to the blood-borne parasite that causes malaria (co-dominance)
What is epistasis?
A form a G xG interaction in which one gene masks the phenotypic expression of another
No new phenotypes are produced by this type of gene interaction
What does epistatic mean?
A gene which masks another’s gene expression
What does hypostatic mean?
A gene whose expression is masked by another
What do quantitative traits mean?
Refers to phenotypes that vary in degree and can be attributed to polygenic effects, I.e. Product of two or more genes and their environment.
E.g. Skin colour affected by additive effects of multiple alleles and exposure to the sun
Give an example of how environments may influence the expression of genes
Fur colour in Himalayan rabbits
White rabbits that develop dark spots on the coldest parts of their bodies (ears and nose)
All body cells have the same genotype,
Maybe this is a product of environmental influences
Reared rabbits in various heats (hot were all white and colder got darker)
