Case 2 Flashcards
Describe the cell cycle.
- G1/G0: a growth phase in which the cell increases its mass
- S: DNA replication
- G2: second growth phase
- Mitosis DNA Replication
Describe the process of DNA replication.
- DNA replication takes place at multiple points in the DNA, called origins of replication (or consensus areas).
- An enzyme called DNA helicase unwinds the double-stranded DNA. At the origins of replication, bifurcated Y-shaped structures (this is the point where the splitting by the helicase starts) known as replication forks appear.
- The synthesis of both complementary antiparallel DNA strands (sense strands) occurs in the 5’prime to 3’prime direction.
- One sense strand, known as the leading strand, is synthesized as a continuous process. The other strand, known as the lagging strand, is synthesized in pieces called the Okazaki fragments, which are then joined together as a continuous strand by the enzyme DNA ligase.
- An enzyme called RNA primase adds a primer to the leading strand.
- DNA polymerase binds to this primer, adding new complementary nucleotides to each strand. (A-T and G-C).
- DNA polymerase can only bind nucleotides in the 5’prime to 3’prime direction.
- Therefore, the lagging strand is synthesised in pieces.
- DNA ligase seals up the fragments into one long continuous strand.
- A subunit of the DNA polymerase proofreads the new DNA.
Describe the process of mitosis.
PROPHASE:
- Chromosomes condense. • Mitotic spindle begins to form. Two centrioles form in each cell, from which microtubules radiate as the centrioles move towards opposite poles of the cell.
PROMETAPHASE:
- Nuclear membrane begins to disintegrate, allowing the chromosomes to spread around the cell. • Each chromosome becomes attached at its centromere to a microtubule of the mitotic spindle.
METAPHASE:
- Chromosomes become aligned along the equatorial plane or plate of the cell, where each chromosome attached to the centriole by a microtubule forming the mature spindle. • At this point the chromosomes are maximally contracted and so are more easily visible. • Each chromosome resembles the letter X in shape, as the chromatids of each chromosomes have separated longitudinally but remain attached at the centromere, which has not yet undergone division.
ANAPHASE:
- Centromere of each chromosome divides longitudinally. • The two daughter chromatids separate to opposite poles of the cell.
TELOPHASE:
- The chromatids, which are now independent chromosomes consisting of a single double helix, have separated completely. • The two groups of daughter chromosomes each become enveloped in a nuclear membrane. • Cell cytoplasm separates (cytokinesis), resulting in the formation of two new daughter cells, each of which contains a complete diploid chromosome complement.
Describe the process of meiosis.
MEIOSIS 1
This is sometimes referred to as the reduction division, because it is during the first meiotic division that the chromosome number is halved. (92 chromatids to 46 chromatids)
PROPHASE 1: Chromosomes enter this stage already split longitudinally into two chromatids joined at the centromere. • Chromosomes become visible as they start to condense. • Homologous chromosome pairs align directly opposite each other, a process known as synapsis. • Each pair of homologous chromosomes, known as a bivalent, becomes tightly coiled. Crossing over (recombination) occurs at points called chiasmata, during which homologous regions of DNA are exchanged between chromatids. • The homologous recombinant chromosomes now begin to separate but remain attached at the chiasmata. • Separation of the homologous chromosome pairs proceeds as the chromosomes become maximally condensed.
METAPHASE 1 • Nuclear membrane disappears. • Chromosomes become aligned on the equatorial plane of the cell where they have been attached to the spindle, as in metaphase of mitosis.
ANAPHASE 1 • Chromosomes now separate to opposite poles of the cell as the spindle contracts.
TELOPHASE 1 • Each set of haploid chromosomes has now separated completely to opposite ends of the cell. • Two new daughter gametes – secondary spermatocytes or oocytes.
MEIOSIS 2: This is similar to mitosis. Each chromosome which exists as a pair of chromatids becomes aligned along the equatorial plane and then splits longitudinally, leading to the formation of two new daughter gametes, known as spermatids or ova.
What are the consequences of meiosis?
When considered in terms of reproduction and the maintenance of the species, meiosis achieves two major objectives: 1. Ensures haploid number of chromosomes in daughter cells. 2. Generating genetic diversity. This is achieved in two ways: • Random assortment. • Crossing over.
How does the risk of Down’s syndrome change with age?
- Risk of DS increases with maternal age
- 17 years risk = 1/1550, 47 years risk = 1/30
Describe the antenatal screening programme. What can come from it?
Blood tests and ultrasound
- Screening for Down’s, Edward’s and Patu syndrome
- High risk results can be confirmed via invasive testing
- High risk cut off 1:150
Anomaly scan at around 20 weeks
- Amnio if possible chromosome abnormality e.g. defects in multiple systems
- Referral to genetics
- Blood test: this is carried out between 9 to 13 weeks of gestation.
- Ultrasound: this is carried out between 11 to 13 weeks of gestation. A special type of ultrasound scan, known as nuchal translucency, measures the pocket of fluid behind the baby’s neck. Babies with Down’s syndrome usually have more fluid in their neck than normal.
Describe the combined test in the antenatal screening programme.
Carried out between 11+2 and 14+1 weeks gestation
- Maternal serum biochemistry measurements of serum beta-HCG and PAPP-A
- Nuchal translucency (measured at the 12 week scan) – measuring the fluid at the back of the baby’s neck
- Age
-> Give someone an individual risk for their pregnancy
Increase nuchal translucency can be indicative of Downs and other genetic diseases – often other chromosome problems
Describe the quad test in the antenatal screening programme.
- 2nd trimester (if you miss the window for the combined test)
- From 14+2 – 20 weeks but optimal 15-19 weeks
- Measures beta-HCG, inhibin A, unconjugated oestriol (Ue3) and alphafetoprotein (AFP) – measuring serum levels in the blood
- Combined is test of choice but quad used for women too late for first trimester screening and in trusts where combined not introduced
- Not quite the same accuracy as the combined test
What is non-invasive prenatal testing?
- Cell-free nucleic acids (DNA & RNA) in blood (cffDNA)
- 10-20% in pregnant woman come from the placenta and represent the fetus
- Can be detected from 7 weeks however the level of cffDNA (cell-free fetal DNA) reaches a level suitable for analysis at different gestations according to what is being tested for
- Already in practice to determine sex for sex-linked disorders
- Non-invasive technique therefore safe to pregnancy
- Results possible from as early as 9 weeks
What is genetic screening?
- This is a way of assessing the likelihood of a baby developing, or already having developed, an abnormality during your pregnancy
- It cannot diagnose conditions, but may help with the decision to have pre-natal diagnostic tests
What is The Abortion Act?
Abortion Act 1967, as amended:
Abortion is legal when a pregnancy is terminated by a registered medical practitioner if two registered medical practitioners are of the opinion, formed in good faith:
a) That the pregnancy has not exceeded its twenty-fourth week and that the continuance of the pregnancy would involve risk, greater than if the pregnancy were terminated, of injury to the physical or mental health of the pregnant woman or any existing children of her family; or
b) * that the termination is necessary to prevent grave permanent injury to the physical or mental health of the pregnant woman; or
c) * that the continuance of the pregnancy would involve risk to the life of the pregnant woman, greater than if the pregnancy were terminated; or
d) * that there is a substantial risk that if the child were born it would suffer from such physical or mental abnormalities as to be seriously handicapped
*there is no time limit on the term of the pregnancies to which grounds b)-d) may apply
The Abortion Act goes on to state that ‘in determining whether the continuance of pregnancy would involve such risk of injury to health as is mentioned in paragraph a) to b)…, account may be taken of the pregnant woman’s actual or reasonably foreseeable environment – if the termination is immediately necessary to save the life or to prevent grave permanent injury to the physical or mental health of the pregnant woman, the pregnancy may be terminated if one registered medical practitioner is of the opinion, formed in good faith that an abortion is justified within the terms of the Act – any treatment for the termination of pregnancy must be carried out in an NHS hospital or in an approved independent sector place – it is good practice to make patients aware of all choices available – they include continuation of pregnancy, with subsequent adoption; continuation of pregnancy and keeping the child; and elective abortion during second and third trimester
What is euploidy?
- Any exact multiples of N are referred to as euploid
- Increase in number of complete sets of chromosomes
- E.g. diploid 2n, triploid 3n, tetraploid 4n
- Have an equal number of all the chromosomes of the haploid set
What is polyploidy?
- Polyploidy is a state in which cells have chromosomes in multiples of N greater than 2N
- Change in the number of chromosome sets – e.g. 3n triploidy, 4n tetraploidy
- More common in plants
What is aneuploidy?
- Aneuploidy is a state in which there is a variation in number of chromosomes that is not in multiples of N
- Variation in the number of a particular chromosome within a set
- E.g. trisomy (2n+1) (one extra chromosome), monosomy (2n-1), nulisomy (2n-2)
- This is more common in animals
- Turner’s syndrome, Down’s syndrome
- Change in the number of chromosomes in each set
Explain triploidy and tetraploidy.
- Triploidy is the commonest form and usually results in a miscarriage of the foetus
- E.g. 69 XXY
- Triploidy arises by:
- fertilisation of an egg by two spermatozoa (dispermy)
- fertilisation of a diploid gamete which results from a failure of maturation of the egg or sperm ?????
- Tetraploidy arises from failure of completion of the first zygotic mitotic division and is incompatible with life
Explain some of the types of aneuploidy.
- An extra copy of a particular chromosome is referred to as trisomy of that chromosome
- Loss of a copy of chromosome is referred to as monosomy of that chromosome
- All complete monosomies of autosomal chromosomes (1-22) are lethal although partial monosomies may be observed in unbalanced translocations
- The only complete monosomy that is not lethal is that of the X chromosome and this presents as Turner syndrome
- E.g. 47XYY – sex chromosomal aneuploidy
- This can result from:
- non-disjunction – failure of chromosomes or sister chromatids to separate at anaphase in cell division
- anaphase lag – delayed movement of chromosomes after separation at anaphase
- The end result of non-disjunction during meiosis or mitosis is one daughter cell with an extra copy and the other daughter cell lacking a copy of the affected chromosome
What is Turners syndrome?
- 45 XO
- Aneuploidy
- Monosomy X
- Autosomal regions on sex chromosomes which means that for some genes you may need to genes worth of it so that causes the problems with just having one X chromosome
