Chromosomes and Inheritance Flashcards
How long do each phase of the cell cycle last?
G1 10-12 hours
S 6-8 hours
G2 2-4 hours
M 1-2 hours
What are the 5 phases of the M phase ?
- Prophase: Chromosomes condense, nuclear membrane disappears, spindle fibres form the centriole.
- Metaphase: Chromosomes aligned at the equator of the cell (here they are the most compact they will be), attached by fibre to each centriole, maximum condensation of chromosome.
- Anaphase: Sister chromatids separate at centromere, separate longitudinally, move to opposite ends of the cell
- Telophase: New nuclear membranes form, each cell contains 46 chromosomes (diploid)
- Cytokinesis: Cytoplasm separate, two new daughter cells are formed.
Describe the basic structure of eukaryotic DNA
Linear structure called chromosomes.
contain Telomeres, centromeres, heterochromatin and euchromatin.
What are telomeres?
Very important in DNA replication.
DNA must be replicated in a 5’- 3’ direction. For the leading stand this can be done in one continuous repeat however in the lagging strand replication must be done in Okazaki fragments.
However when replication reaches the end of the chromosome the DNA polymerase is removed and it leaves a gap. This gap is known as the end-replication problem and is filled in with nucleotides by the enzyme Telomerase.
Note that telomerase is only found in some cells i.e. stem cells.
What are centromeres?
Centromeres are the constricted region that joins sister chromatids. They contain repetitive DNA sequences which is called satellite DNA. Centromeres are the site of kinetochore. Kinetochore is the protein complex that binds to microtubules. Centromeres and kinetochore are therefore required for chromosome separation during cell division.
What is chromatin?
Chromatin is a mixture of DNA, proteins and RNA.
What are the two types of chromatin?
Heterochromatin has a condensed structure and contains silenced genes (it is condensed DNA).
Euchromatin has an open structure and contains active genes (this is extended DNA).
What are extragenic sequences?
Regions of the genome that do not code for protein. Extragenic sequences can be tandemly repeated DNA sequences (such as satellite found in centromeres and telomeres and minisatellite DNA used for DNA fingerprinting) and Highly repeated interspersed DNA sequences (which makes up about 45% of the genome) for example SINEs (Short interspersed nuclear elements) and LINEs (long interspersed nuclear elements)
How is DNA packed?
DNA is packaged with histone proteins to form chromatin. Histones have positive charge. Chromatin is then packaged into units called nucleosomes (which look at bit like beads on a string) Nucleosomes contain 146 bp, where DNA wrapped (1.8 turns) around core of 8 histone proteins.
These nucleosomes are wrapping further. (About 6 nucleosomes per turn). This forms a ‘solenoid’ structure which has compacted DNA by about factor of 40.
Why is DNA packed into chromatin ?
- It allows negatively charged DNA neutralised by positive charged histone proteins
- It mean DNA takes up less space
- Inactive DNA can be folded into inaccessible locations until required
- Inactive chromatin characterised by specific histone covalent modification (e.g. methylation)
What are the different stages in the folding of DNA into a chromosomes?
Nucleosome
Chromatin fibre
Fibre-scaffold complex
Chromosome
Describe the structure of the two arms of a chromosome
The centromere separates the each chromatid into the p arm (the smaller arm) and the q arm.
What are the names given to chromosomes based on where there centromere is ?
If a chromosomes centromere is middle then it is called metacentric, if the centromere is a bit off centre then it is called submetacentric and if the centromere is very near the end of the chromatid it is called acrocentric.
How can a chromosome be identified?
The Heterochromatin and Euchromatin can be stained. This produces the striped effect that you can see in this image and can be used to help identify the chromosome present in the sample.
What is G-banding?
G-banding produces about 550 bands per cell, this allows chromosomes to be identified and paired up.
This is called a Karyotype.
Autosome are the non sex chromosomes.
How else can DNA be identified?
Fluorescent in situ hybridisation (FISH)
What are the different types of FISH ?
- Unique sequence probes
- Centromeric probes. This is useful for determining chromosome number
- Telomeric probes. This is useful for detecting sub telomeric rearrangements. These are often present in children with unexplained mental retardation
- Whole chromosome probes. This is a cocktail of probes covering different parts of a particular chromosome. It is used with different fluorescent dyes. Spectral karyotype. Useful for detecting translocations and rearrangements
What complex modifies and displaces histones?
Chromatin remodelling complexes.
What does a semi-conservative process mean?
one half of each molecules of DNA is old and one half is new.
What is meiosis?
Meiosis is the process of cell division in germ cells (gamete).Here diploid cells (in ovaries and testes) divide to form haploid cells. Chromosomes are passed on as re-arranged (recombined) copies and this creates genetic diversity.
How does meiosis differ in males and females ?
Miosis is the same process in both males and females however they produce a different type of cell. Both go though several stages, with different timing in males and females. Sperms go through more cell divisions than eggs do – more chance of mutation
Oogenesis = process of egg formation
Spermatogenesis = process of sperm formation
Which parent does the mitochondrial DNA come from?
Mother
What happens in fertilisation?
two haploid cells (egg, sperm) form 1 diploid cell (zygote) which then develops into a embryo.
What is X-inactivation?
Females don’t need half two X chromosomes therefore in each cell one is randomly inactivated.
What are the three categories of chromosome abnormalities?
Numerical, structural or mutational.
What are the different types of numerical abnormality?
Trisomy’s include Patau (47, XX +13) which causes mental retardation , Edwards (47, XY +18) which causes severe developmental problems, down syndrome (47, XX +21) which causes a low IQ, and Klinefelter (47, XXY) which causes tall stature and infertile males.
Monosomy include turners (45,X) which causes short stature and infertility in women.
Turners and Klinefelter are sex linked conditions.
What are the different types of structural abnormalities ?
- Balanced or unbalanced rearrangement. (No DNA loss but can be detrimental in later generations)
- Translocations. These can be Reciprocal: involving breaks in two chromosomes with formation of two new derivative chromosomes or Robertsonian: fusion of two acrocentric chromosomes
- Deletions
- Inversions (A type of Balanced rearrangement)
What are the different mutational abnormalities?
- Silent is synonymous, i.e. the mutation doesn’t alter the amino acid and therefore there is no effect. CGA (Arg) to CGC (Arg).
- Missense is a substitution mutation that will alter one amino acid i.e. CGA (Arg) to GGA (Gly)
- Nonsense is a substitution mutation that will alter one amino acid resulting in the premature end of a polypeptide chain i.e. CGA (Arg) to TGA (Stop)
- Deletion is a frameshift mutation altering ever amino acid after that point i.e. CGA (Arg) to CG
- Insertion is a frameshift mutation altering ever amino acid after that point i.e. CGA (Arg) to CCGA
How can mutations be detected?
Polymerase chain reaction (PCR). Gel electrophoresis. RFLP ARMS DNA sequencing
What is PCR
Polymerase chain reaction (PCR). Allows the amplification of DNA. This requires Sequence information Oligonucleotide primers, DNA, Nucleotides and DNA polymerase. It has three stages denaturation, anneal and extend. This is good because it is fast, easy to use, sensitive and robust. It is used in DNA cloning, DNA sequencing, gene identification and forensic medicine.
What is gel electrophoresis?
Allows the separation of DNA. It is done by Applying an electric field, DNA is negatively charged and so separate through agarose gel matrix. the DNA fragments can then be visualised.
What is restriction fragment length polymorphism? (RFLP)
Restriction fragment length polymorphism (RFLP) analysis is used to identify variation in DNA. It uses restriction endonucleases which recognise and cut DNA. This is good because it is simple and cheap but it requires gel electrophoreses.
What is ARMS?
Amplification refractory mutation system (ARMS). This is used to detect mutations. A special primer is added that will replicate a chain of DNA if the wild type (normal) mutation is present and another special primer is added that will replicate a chain of DNA if the mutation is present. The presence of absence of these replicated chains can be used to determine if the mutated gene is present. This process is good because it is cheap, and no labelling is required however it does require sequence information and there is a limited amplification size.
What is DNA sequencing?
DNA sequencing. Uses dideoxy nucleotides to detect mutations. However it requires expensive equipment.
What is mendelian inheritance?
Mendelian inheritance is governed by the law of dominance, law of segregation and law of independent assortment.
A Mendelian conditions can arise from multiple different mutations
What are the type types of mendelian inheritance?
Recessive inheritance
Dominant inheritance
What is recessive inheritance?
If someone has one copy of the mutated gene then they are called a carrier but wont have symptoms of the condition. If someone has two copies of the mutated gene then they would be suffers.
What are some examples of recessive inheritance?
Some examples include sick cells disorders which has an abnormal HB gene. If someone has two copies of the gene then the person will surfer from the condition. They will have pain, cold, dehydration, infections, jaundice, stroke, etc. It can also lead to anaesthetic issues. If you have sickle cell anaemia you are less likely to get malaria which therefore drives its prevalence up.
Cystic fibrosis is another example. It effects many organs in the body for example in the lungs the airways are clogged with thick, sticky mucus.
What is dominant inheritance?
If someone has one copy of the mutated gene then they are called a suffer. If someone has two copies of the mutated gene then they would be suffers.
What is an example of dominant inheritance?
An example is Huntington’s disease which is a neuro-degenerative condition.
What is a sex linked condition ?
A dominant or recessive condition coded for on the X Chromosome.
Who do X linked condition effect most ?
Conditions coded for on the X chromosome largely effect men and can skip generations.
Examples of X linked conditions
For example muscular dystrophy which is a recessive condition however because men only have one X chromosome if they are a carrier they will suffer from it. It causes weak muscles and is fatal in early adulthood.
Another X linked recessive condition is haemophilia. If the father is a suffer then all the daughters will be carriers (girls always have one X chromosome from there father and if the father only has one) and non of the boys will be suffers. If the mother is a carrier then there will be a 50% chance of every child inheriting the mutated X chromones form the mother.
What is a non-mendelian inheritance?
Non-mendelian inheritance does not fit with the laws of Mendelians inheritance.
What are the patterns that non-mendelian inheritance does follow?
Incomplete penetrance Genomic imprinting Extranuclear inheritance Anticipation Complex
What is incomplete penetrance?
Penetrance is the frequency with which a trait is manifested by individuals carrying the gene. Penetrance can be used to determine if preventative treatment should be performed. For example, if someone has the BRCA2 mutation then they might have a double mastectomy because it has a high penetrance.
Penetrance however is not just genetic; it is also environmental.
What is genomic imprinting?
Genomic imprinting is an epigenetic modification, a random inactivation of parts of an offspring’s DNA. A gene is inactivated by the binding of a methyl group to a cytosine in a process of methylation. This binding converts cytosine to 5’methylcytosine (or mC). mC induces structural adaptation of chromosomal region so as to perpetuate altered activity states- stops it being available for translation
Genomic imprinting can be causes by deletions, point mutation, imprinting errors and uniparental disomy. Uniparental disomy occurs when both chromosomes in the pair are inherited from one parent. Gynogenic is when two material genomes are inherited and causes ovarian teratoma, hydatidiform mole is caused when two paternal genomes are inherited.
What are examples of genomic imprinting?
Angelman syndrome which causes epilepsy and mental retardation, and Prader-Willi syndrome which causes marked obesity and mental retardation are examples of imprinting disorders.
What is extranuclear inheritance?
All mitochondrial DNA is from the mother and it has a high mutation rate as a result of a lack of efficient DNA repair system, lack of protective proteins i.e. histones and damage caused by free radicals.
Homoplasmy is when there is a low level of mutations in the mitochondria (the mitochondria are all very similar). Heteroplasmy is when there is a lot of variation in the mitochondrial as a result of high mutation rates.
What is anticipation?
Anticipation is when the disease presents at earlier age and/or increasing severity in succeeding generations. For example, huntingtins disease or fragile X syndrome.
What is complex ?
This is where multiple genes are involved in a condition for example heart disease or autism.
What is population genetics?
If selective pressures change, importance of different alleles may change.
Because deleterious alleles will decrease a person’s fitness (ability to survive and pass on their genes). The level of care is also important in whether offspring survive and reproduce.
How can the allele frequency in a population be determined?
p + q = 1
or p2 + 2pq + q2 = 1
What does the hardy Weinberg equations predict?
That allele and genotype frequency in a population will remain constant as long as there are no mutations, no migration, no natural selection pressure, random mating, large population and equal allele frequency in both sex.
What are examples of non-random mating?
Assortative mating (choosing of partners due to shared characterises) Consanguinity (marriage between close blood relatives)
What is natural selection?
Natural selection is a gradual process by which biological traits become either more or less common in a population.
What is positive selection?
Positive selection however is the increases reproductive fitness and prevalence of adaptive traits giving a Heterozygote advantage (for example sickle cell anaemia gives resistance to malaria)
What is negative selection?
Negative selection is the reduction of reproductive fitness, decreases the prevalence of traits and gradual reduction of mutant allele.
What is genetic drift?
the random fluctuations increase of decrease of a trait form one generation to the next due to sexual reproduction
What is statistical drift?
Statistical drift of gene frequencies is due to change or random event
What is the founder effect?
The founder effect is the increase of decrease of trait due to a small subset of a large population sees mating with the rest of the population
What is the bottleneck effect?
The bottleneck effect causes the population size to be drastically reduced for one of more generations.
Why is a large population required in the equation?
Large population can balance fluctuations, but small populations cannot.
What is a proto-oncogene?
A proto-oncogene is a normal gene that codes for proteins to regulate cell growth and differentiation. If it is mutated it forms an oncogene that can accelerate cell division. Cancers arise when this gene is stuck in ‘on’ mode.
What is a tumours suppressor gene?
Tumour suppressor genes are the cell’s breaks for growth. Mutations here allow the cell cycle and to increase and apoptosis to decrease.
What are DNA damage-response genes?
DNA damage-response genes are the repair mechanics for DNA, when these fail it can cause HNPCC and MSI. MMR corrects errors that spontaneously occur during DNA replication, if this doesn’t work errors accumulate. Microsatellites are repeated sequences of DNA that can be made of repeating units of 1 – 6 base pairs. MSI is the phenotypic evidence that MMR is not functioning normally – genetic hypermutability
What are the different types of tumours?
benign, dysplastic (benign but could become malignant) and malignant.
How can genetics give rise to cancers?
Cancer can be caused by autosomal recessive syndromes where both copies of the gene have inherited mutations and multiple modifier genes of lower genetic risk. They can also arise from De Novo mutations where the mutation occurs in the germ cell of a parent with no family history of hereditary cancer syndrome.
Give some examples of cancer than can be genetic
Retinoblastoma
Breast cancer (BRCA1 and BRCA2)
Ovarian (BRCA1 and BRCA2)
Colorectal (MLh1, MSH2, MSH6 and PMS2)
