Genes and Early Embryology

Question 1

Describe in detail the chemical mechanisms in the actual protein synthesis process.

Answer 1

initiation - arrangement of translational system components, ribosomes recognise AUG start codon.

elongation - addition of amino acids to carboxyl end of growing chain, translocation occurs.

termination - RF binding causes hydrolysis of the bond linking the peptide to tRNA in the P site.

Question 2

Describe the events which can modify a protein after it has been synthesised; i.e. post translational processing.

Answer 2

attached to the ribosome when chain modified - they are cotranslational. If this is done after synthesis they are posttranslational.

Question 3

Describe the signal hypothesis which aims to explain how membrane bound or secreted proteins are directed to their ultimate destinations.

Answer 3

Small ubiquitin-related modifier (SUMO) addition can signal cellular localization.

Question 4

Explain in very broad terms how all proteins are directed to the site of their action; i.e. the idea of chaperone proteins which can monitor protein folding and protein movement around the cell.

Answer 4

Ribosome associated chaperones will help a protein to fold. The ribosome’s exit channel is too narrow to permit secondary structure formation. Many polypeptide chains are modified before use.

Question 5

State examples of antibiotics which specifically inhibit protein synthesis in prokaryotic, eukaryotic or both types of cells.

Answer 5

prokaryotic - tetracycline

eukaryotic - chloramenphenicol

Question 6

Describe the design, strengths and limitations of cohort studies

Answer 6

compare risk of one group to another using healthy individuals and by looking forwards in time

strengths - allow measurement of incidence, multiple outcomes and exposures can be studied, reducued chance of selection and recall bias

limitations - expensive and time intesive, inefficient for rare diseases, difficulty of confounding, likely dropouts and attrition bias

Question 7

Calculate and interpret an incidence rate ratio

Answer 7

The rate ratio is calculated as the rate of disease in the exposed group ÷ rate of disease in the unexposed group.

Question 8

Interpret the results of a survival analysis

Answer 8

This allows us to describe and compare the number of people who suffer an event of interest and the time at which the event occurs.

Question 9

Describe the structure of the female reproductive system only in sufficient detail for subsequent understanding of the sites of fertilisation and implantation; and the ovarian cycle.

Answer 9

The ovum is shed into the abdominal cavity and is captured by the fallopian tube. the egg is implanted in the uterus. the fallopian tube is divided into the infundibulum, the ampulla, the isthmus, and the interstitial (intramural)

Question 10

Explain the major differences in gametogenesis between male and female and the structure of male and female gametes.

Answer 10

males: mitosis followed by meiosis in the testes leads to haploid spermatozoa. continuous from puberty, takes 9 weeks, 300mill per ejaculate.
sperm: motile, low cytoplasmic to nuclear ratio, fluid from other glands added prior to ejaculation
females: meiosis in ovary leads to haploid ovum, discontinuous as primary oocytes suspended partway through meiosis, 5-12 primary oocytes continue each monthly cycle but dont complete meiosis untikl fertilisation
ovum: non motile, very high cytoplasmic to nuclear ratio

Question 11

Discuss the terms diploid and haploid; preembryo, embryo and fetus.

Answer 11

dipolid - full set of chromosomes

haploid - half set of chromosomes

preembryo - a human embryo or fertilized ovum in the first fourteen days after fertilization, before implantation in the uterus has occurred.

fetus - The fetal period begins 8 weeks after fertilization of an egg by a sperm and ends at the time of birth.

Question 12

Explain the process of fertilisation, its site, the prevention of polyspermy and the unequal cytoplasmic contribution of the two gametes.

Answer 12

• Chemoattractants are released from cumulus cells upon ovulation to make sperm motile again.
• Sperm requires capacitation (conditioning) in the female reproductive tract during which the acrosomal region loses its glycoprotein coat.
• The polar body is present because the egg is suspended halfway in meiosis and this is the other half of the genetic material
• sperm penetrates the zona pellucida, the cell completes the second meiotic division
• Acrosomal enzymes help to disperse the corona radiata and aid in the penetration of the zona pellucida
• permeability of the zona pellucida is altered to prevent further penetration
• ovum shrinks forming the perivitelline space
• Cytoplasmic contribution is unequal - all organelles are from the female.

Question 13

Describe cleavage and morulation; the relative rates of production of DNA and cytoplasm; cytoplasmic packaging.

Answer 13

after 30 hours, mitosis occurs forming two blastomeres. cleavage continues until a morula is formed. The cytoplasm to nuclear ratio has fallen to near normal

Question 14

Describe the development of the blastocyst.

Answer 14

The morula is still free in the uterine cavity. The morula cells undergo compaction. Tight junctions are established between surface cells and the zona pellucida begins to break down.

After around 5 days post fertilisation, a cavity develops and the blastocyst is formed.

Question 15

Describe the differentiation of an inner cell mass and a trophoblast and their eventual fates (in general terms) include when and where it develops.

Answer 15

The trophoblast is invasive, ingestive and digestive. A decidual reaction occurs in the uterine lining leading to increased secretory function. Derivatives of the trophoblast form the placenta. produces extramembryonic mesoderm

The inner cell mass forms the embryo and some membranes. The beginning of primitive ectoderm and endoderm occurs.

Question 16

Describe implantation include when and at what stage the conceptus passes into the uterine cavity; the disappearance of the zona pellucida; the invasive nature of the trophoblast; the possibility of ectopic implantation; and the decidual reaction in the uterine lining.

Answer 16

At about 6 days the blastocyst adheres to the endometrium. The primitive ectoderm (epiblast) surrounds the amniotic cavity and the primitive endoderm (hypoblast) surrounds the cavity of the yolk sack. the decidual reaction occurs. The chorionic cavity allows the conceptis to expand and the baby to grow. zona pellucida is lost

Trophoblast invasion of the uterus is a necessary step at implantation of the human blastocyst. It leads to envelopment of the blastocyst by the endometrium

An ectopic pregnancy is the implantation of the egg into the uterine tube

The endometrium then undergoes the decidual reaction. Derivatives of the trophoblast form the placenta. Glycogen and lipid distended cells form and glands swell more to provider nutrients

Question 17

Discuss the development of the bilaminar disc include the appearance of ectoderm and endoderm, the formation of the amniotic cavity and yolk sac.

Answer 17

bilaminar disc - The ectoderm of the amnion and the endoderm of the yolk sac is continuous with the bilaminar disc. Where ectoderm and endoderm lie against each other, a flattened bilaminar disc is produced from which will form the majority of the fetus.

The primitive ectoderm (epiblast) surrounds the amniotic cavity and the primitive endoderm (hypoblast) surrounds the cavity of the yolk sack.

Question 18

Explain the development of extraembryonic mesoderm, the chorionic cavity (i.e. extraembryonic coelom) and the connecting stalk.

Answer 18

The extra embryonic mesoderm is left covering the amnion and yolk sac and lining the trophoblast. These 2 layers of mesoderm are joined by the connecting stalk. The chorionic cavity allows the conceptis to expand and the baby to grow.

Question 19

Describe the timing of these events. (implantation)

Answer 19

day 6 - blastocyst adheres to endometrium, implantation begins
day 10 - the blastocyst is completely embedded and epithelial continuity is restored.
week 2 - week of twos: endo and ecto, amniotic and yolk, cytotrophoblast and the syncytiotrophoblast

Question 20

Discuss the formation of intraembryonic mesoderm, the appearance and function of the primitive streak and the formation of the trilaminar disc.

Answer 20

The epidermal cells begin to divide and migrate between ecto and endoderm in the region of the primitive streak to form intraembryonic mesoderm. The bilaminar germ disk differentiates itself further into a trilaminar embryo

primitive streak - Cells from the ‘head’ (rostral) end of the primitive streak form a midline structure known as the notochord.

Question 21

Describe the fate, in very general terms, of the three germinal layers.

Answer 21

endoderm - organs such as stomach and colon

ectoderm - epithelial tissue, neuroectoderm

mesoderm - muscles

Question 22

Compare the properties of DNA and RNA.

Answer 22

DNA - solely in nulceus, double-stranded, T instead of U

RNA - intermediate for protein synthesis, single strand, U instead of T

Question 23

Describe the structure and properties of hnRNA, mRNA, rRNA, tRNA and ribosomes.

Answer 23

hnRNA - refers to the large pre‐mRNAs of various nucleotide sequences that are made by RNA Polymerase II, and processed in the nucleus to become cytoplasmic mRNAs.

mRNA - Messenger RNA (mRNA) is a single-stranded RNA molecule that is complementary to one of the DNA strands of a gene. The mRNA is an RNA version of the gene that leaves the cell nucleus and moves to the cytoplasm where proteins are made.

rRNA - rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosomal DNA (rDNA) and then bound to ribosomal proteins to form small and large ribosome subunits.

tRNA - a type of RNA molecule that helps decode a messenger RNA (mRNA) sequence into a protein. tRNAs function at specific sites in the ribosome during translation, which is a process that synthesizes a protein from an mRNA molecule.

ribosome - the small and large ribosomal subunits. Each subunit consists of one or more ribosomal RNA (rRNA) molecules and many ribosomal proteins (RPs or r-proteins).

Question 24

Describe the reaction catalysed by RNA polymerase enzymes.

Answer 24

RNAP (RNA polymerase) binds to initiation sites through base sequences known as promoters. In prokaryotes, these are recognised by an RNAP sigma factor.

The binding of RNAP holoenzymes leads to DNA melting (separation) in its vicinity (transcription bubble). This allows complementary RNA strand synthesis and the bubble travels with RNAP.

Question 25

Describe the structure of a eukaryotic gene.

Answer 25

A typical eukaryotic gene consists of a set of sequences that appear in mature mRNA (called exons) interrupted by introns.

Question 26

Describe the events involved in the transcription of a eukaryotic gene.

Answer 26

This is the joining together of exons. Humans can have up to 50 introns per gene. There are around 7 types of introns. Introns in the GU-AG probably act as recognition for RNA-binding proteins. The spliceosome carries out splicing. This forms small ribonucleoproteins and allows folding.

Question 27

Identify the sites of action of inhibitors such as amanitin, actinomycin D and rifampicin.

Answer 27

Rifamycin B is produced by streptomyces bacteria. It inhibits prokaryotic but not eukaryotic transcription. It prevents elongation and the inactivated RNA polymerase remains bound and blocks further initiation.

Actinomycin D is an anticancer agent. It binds to duplex DNA and inhibits DNA replication and transcription in eukaryotes and prokaryotes. It interferes with polymerase passage.

The death cap mushroom is a killer. It contains amatoxins. The alpha amanitin binds to RNAP II and blocks the elongation step. It binds beneath the ploymerase’s bridge helix. It acts slowly and causes liver dysfunction.

Question 28

Define personality and describe two common theories of personality.

Answer 28

Personality refers to individual differences in characteristic patterns of thinking, feeling and behaving. There are two personality theories of focus: the UPPS-P multidimensional approach to impulsive personality and the Big Five factor model.

UPPS-P: negative urgency, premeditation, perseverance, sensation seeking, positive urgency.

Big Five: conscientiousness, neuroticism, extroversion, agreeableness, openness.

Question 29

Outline some examples of how personality could have an impact on health.

Answer 29

Zvolensky found that a higher openness and neuroticism score were significantly associated with increased risk of any lifetime cigarette use.

High conscientiousness was positively related to intent to eat fruit and veg and actual fruit and veg intake. Those higher in conscientiousness were more likely to follow through with their intentions.

Question 30

Explain why personality could influence behaviour change or influence adherence.

Answer 30

Non-adherence is a major obstacle in treating chronic disease. The results of a study investigating this found that neuroticism, agreeableness and conscientiousness influenced adherence behaviour. Most neurotics were less likely to adhere, showing a negative relationship. Those who scored highly in agreeableness and conscientiousness were related to better adherence.

Question 31

Understand the common inheritance patterns, X linked recessive and Autosomal Recessive inheritance.

Answer 31

X-linked: X-linked recessives are males with one copy of the abnormal gene on the X-chromosome affected. In this case, there is no male to male transmission and carrier females are unaffected. All men who inherit the mutation are affected and it can appear to ‘skip’ individuals.

autosomal recessive: Autosomal recessives are homozygotes with two copies of the abnormal gene affected.

Question 32

Know the carrier rates in the general population for common autosomal recessive conditions e.g. cystic fibrosis, phenylketonuria.

Answer 32

CF - 1/25

Phenylketonuria - 2%

Question 33

Understand the Hardy-Weinburg equilibrium and how to use it to calculate carrier rates from the incidence of a condition in the general population.

Answer 33

The Hardy-Weinberg principle allows the calculation of carrier rates once the incidence of a condition is known as long as the gene frequency is in equilibrium, can use carrier frequency in calculations.

Question 34

Understand the factors that can influence the Hardy-Weinburg equilibrium and their effects on gene frequency in the general population.

Answer 34

• non-random mating
• Consanguinity
• sufferers reproducing
• selection advantage
• small populations

Question 35

Understand the basis of population screening programmes e.g. antenatal down syndrome, haemoglobinopathy, PKU, CF.

Answer 35

Ultrasound, NT scan to see neck thickness, biochemical serum screening, MSAFP assay can see down syndrome, chronic villus sampling, amniocentesis

Question 36

Understand the differences between Mendelian and multifactorial inheritance

Answer 36

mendelian - Mendelian inheritance refers to an inheritance pattern that follows the laws of segregation and independent assortment in which a gene inherited from either parent segregates into gametes at an equal frequency.

multifactorial - No one gene is dominant or recessive to another, instead there is a cumulative effect.

Question 37

Understand the concepts of heritability, and the liability threshold model.

Answer 37

The sum of environmental influences and genetic predisposition gives a person’s liability to be affected, if the threshold is exceeded the condition results.

Question 38

Know the factors that can influence empiric recurrence risks

Answer 38

relation, severity, number of relative affected, higher risk if lower risk gender affected

Question 39

Know the screening tests offered during a routine pregnancy e.g. scans and trisomy screening.

Answer 39

ultrasound, NT scan, biochemical serum screening, MSAFP assay, fetal anomaly scan at 20 weeks.

Question 40

Understand the techniques used during a pregnancy for targeted prenatal diagnostic testing, in particular CVS and amniocentesis.

Answer 40

• CVS - sample of placenta
• amniocentesis - sample of amniotic fluid
• cordocentesis (fetal blood sampling)
• fetal tissue biopsy.

Question 41

Be aware of preimplantation genetic diagnosis and its clinical use for families at risk of a serious genetic condition.

Answer 41

This is the process of testing embryos produced by IVF for inherited disorders. It is suitable for couples at a substantial risk of transmitting a serious genetic condition to their children (such as chromosome translocations, X-linked disorders and some single gene disorder). It is not available for all conditions. Considerable clinical, laboratory and counselling preparation is required.

Question 42

Describe the induction of the neural plate by the notochord, its subsequent conversion to a groove and finally to a tube.

Answer 42

the neural folds convert the neurl plate into the nerual groove.

Question 43

Describe the division of the intraembryonic mesoderm into paraxial, intermediate and lateral plate columns. Describe the fate, in general terms, of these mesodermal columns; in particular, the development of somites and their innervation.

Answer 43

• the lateral plate mesoderm forms a horseshoe cavity. it is split into somatopleuric mesoderm (striated muscle) and splanchopleuric mesoderm (smooth muscle)
• At the beginning of the fourth week, the paraxial mesoderm begins to form paired cuboidal bodies known as somites (or segments).
• The Intermediate mesoderm becomes nephrotome (which forms the genitourinary system)
• Each somite receives a segmental spinal nerve, which follows that tissue wherever it migrates.

Question 44

Discuss the development and fate of the intraembryonic coelom and discuss the alteration in shape and partition of the intraembryonic coelom.

Answer 44

The edges of the amnion grow downwards towards the yolk sac. The folding greatly reduces the communication between the intra and extra embryonic coelom. In the region of the umbilicus, a connection between the gut tube and the yolk sac remains. This is the vitello-intestinal duct.

Question 45

To be able to list the principal reasons for keeping medical records.

Answer 45

• provide information about patient care, drug and treatments given
• legal reasoning
• for other doctors when handing over a patient
• accurate history of a patient

Question 46

To identify the characteristics of good and poor medical records.

Answer 46

good: legible, good detail, limited abbreviations, includes date and two identifiable patient details, clear
bad: longwinded, too short, lots of abbreviations, illegible, no clear dates or times

Question 47

To reactivate prior knowledge of the basic principles of information governance

Answer 47

only people who need access to patient notes should have them, notes for your own study should be no identifiable, notes should be professional

Question 48

List the common types of mutation seen in clinical practice and be able to give a brief explanation of each nonsense, missense, frameshift, triplet repeats.

Answer 48

nonsense - a change in DNA that causes a protein to terminate or end its translation earlier than expected.

missense - is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid.

frameshift - the insertion or deletion of a nucleotide in which the number of deleted base pairs is not divisible by three.

triplet repeat - too many copies of a certain triplet

Question 49

Compare their possible effects eg gain, loss or partial loss of function mutations.

Answer 49

harmful mutations can cause genetic disorders or cancer, most mutations have no effect, some could be advantageous and make survival more likely.

Question 50

Describe the concept of allele and locus heterogeneity.

Answer 50

heterogeneity is when mutations in different genes in a pathway may give the same syndrome. locus heterogeneity is when yndromes often result from malfunction of physiological pathways.

Allelic heterogeneity is the phenomenon in which different mutations at the same locus lead to the same or very similar phenotypes.

Question 51

Outline the common forms of mutation analysis employed in the laboratory.

Answer 51

PCR is a method of gene amplification. It requires tiny quantities of starting material and produces huge amounts of the target product. The PCR product can then be analysed using a variety of assays.

Methylation Specific PCR can be can be used to detect imprinted or epigenetically silenced alleles. The DNA is modified by a bisulphite reaction which converts non-methylated cytosines to thymine. Methylation specific primers can then be used to test for the presence or absence of a PCR product.

Question 52

Compare linkage/gene tracking and mutation analysis and give examples of their use in a clinical setting.

Answer 52

gene tracking A method for determining the inheritance of a particular gene in a family. It is used in the diagnosis of genetic diseases, such as cystic fibrosis and Huntington’s chorea.

Question 53

Describe the development of the umbilical region with the consequent separation of the intra and extraembryonic coelomic cavities. Describe the structure of the umbilical cord.

Answer 53

The remnants of the yolk sac for the vitello-intestinal duct. The allantois is sucked into the umbilical cord, and two umbilical arteries and an umbilical vein form. The umbilical cord is formed by the region of constriction.

Question 54

The way different cells are derived from different lineages and the role of the stem cell

Answer 54

Totipotent stem cells can give rise to all cell types found in the adult organism, plus extraembryonic cells. Pluripotent stem cells can give rise to all 3 of the germ layers. As development proceeds, stem cells may lose their pluripotency. Multipotent stem cells can give rise to a restricted number of different cell types and adult stem cells.

Question 55

Recognise a normal male and female karyotype, both written and visually.

Answer 55

Girls and women typically have two X chromosomes (46,XX karyotype), while boys and men usually have one X chromosome and one Y chromosome (46,XY karyotype).

Question 56

Give one common variation seen in a normal karyotype.

Answer 56

metacentric, acrocentric, and submetacentric chromosome shape

Question 57

Outline the technique of Fluorescent In Situ Hybridisation and discuss common applications.

Answer 57

F.I.S.H is fluorescence in situ hybridisation. A segment on single stranded DNA is labelled with a fluorescent tag and is then hybridized to target DNA (chromosomes) attached to a slide. It hybridised with its matching DNA sequence.

Question 58

Outline methods of cytogenetic analysis used in a service laboratory.

Answer 58

The sample must be fresh, and needs to be divided. Blood is not dividing, so mitogen PHA is used to persuade the cells to divide.

Question 59

List four common abnormalities of chromosome number and for each give brief clinical details of a clinical example.

Answer 59

• down syndrome, flat facial profile and small ears, frequent autism, cardiac defects
• edwards syndrome, small mouth, clenched hands, congenital heart disease
• patau syndrome, scalp defects, cleft lip and palate, brain malformation
• turner syndrome, short stature, webbed neck, infetility, only in girls.

Question 60

Describe common chromosome anomalies including translocations, duplications, deletions, marker chromosomes and be able to outline their possible implications for a patient.

Answer 60

translation - A child who has an unbalanced translocation may have learning disabilities, developmental delay and health problems. The seriousness of the disability depends on exactly which parts of which chromosomes are involved and how much missing or extra chromosome material there is.

duplication - Some individuals have no symptoms, while others may have features such as a large head size (macrocephaly); mild to moderate developmental delay and learning difficulties; autism or autistic-like behavior

deletion - Most have structural abnormalities of the brain, and seizures occur in more than half of individuals with this disorder. Affected individuals usually have weak muscle tone ( hypotonia ) and swallowing difficulties ( dysphagia ).

marker chromosomes - The significance of a marker is variable as it depends on what material is contained within the marker.

Question 61

List three common clinical situations in which cytogenetic analysis might be helpful.

Answer 61

recurrent miscarriage, screening in pregnancy, infetility

Question 62

Describe the composition of amniotic and chorionic membranes and their eventual fusion.

Answer 62

The ectoderm produces amniotic epithelium (made of ameloblasts) and comes to surround the amniotic cavity.

Cavities form in the extraembryonic mesoderm so that it forms a mesodermal lining of a new cavity - the chorionic cavity.

The amniotic cavity enlarges faster than the chorionic cavity and gradually obliterates it.
Eventually the amnion and chorion join and the fetus floats in the amniotic fluid

Question 63

Discuss the preferential proliferation of the placenta into the decidua basalis.

Answer 63

The side of the uterus where implantation hasn’t taken place is known as the decidua parietalis. The side where the embryo has implanted is known as the decidua basalis. The area that covers the implanted area is known as the decidua capsularis. The expanding embryo and its covering being to obliterate the uterine cavity. The decidua capsularis eventually fuse with the decidua parietalis.

Question 64

Discuss the production of syncytiotrophoblast and cytotrophoblast.

Answer 64

The trophoblast differentiates into the cytotrophoblast and the syncytiotrophoblast. It contributes to the formation of the extraembryonic mesoderm.

Question 65

Describe the formation of blood lakes (lacunae) and the development of the placental circulation.

Answer 65

From days 12 to 13, cytotrophoblast mitosis produces more syncytiotrophoblast. This erodes, plugs and remodels maternal vessels and, when the plug is fully removed (at around 8 to 12 weeks), a functioning uteroplacental circulation is established. The enlarging lacunae are filled with maternal blood.

On day 16, fetal origin villi grow into blood-filled lacunae and these come to develop fetal blood vessels which connect to the umbilical arteries and veins. Exchange of gases can now take place between the mother and the child’s circulatory system.

Question 66

Describe the development, structure and function of primary, secondary and tertiary villi.

Answer 66

When placental villi first form they are called primary stem villi. They have a core of cytotrophoblast and are covered by a layer of syncytiotrophoblast, this is at around week two.

The secondary villi have developed a core of extra embryonic mesoderm inside the two trophoblast layers, this is around week three.

Tertiary villi have developed fetal blood vessels within the mesodermal core, this also occurs at week three. Stem cell branch in intermediate and terminal villi.

Question 67

Describe the nature of the fetomaternal or intravascular barrier.

Answer 67

This term is used to describe tissue layers between maternal and fetal bloods. In the first trimester, there are few villi but they are large and there are central fetal vessels so the exchange surfaces are small and the distances are large.

The barrier comprises a layer of syncytiotrophoblast, a complete layer of cytotrophoblast, substantial mesoderm and the endothelium of fetal vessels.

Question 68

Recount and, where appropriate, describe the stages of eukaryotic gene expression and where regulation can occur.

Answer 68

During splicing, the introns are spliced out as they are non-coding. Splicing can regulate gene expression post ransciptionally to remove exons, leading to different forms of a protein.

The nucleolus rDNA forms ribosomal subunits, which are transported through the nuclear pore in the nuclear membrane and into the cytosol. When in the cytosol, the messenger can be degraded or sequestered in its inactive form.

Proteins produced from the ribosome will fold before becoming functional. Some of these proteins are degraded. The protein is then processed, compartmentalised and secreted.

Question 69

Understand the importance of transcriptional control to the overall control of gene expression.

Answer 69

Transcriptional regulation is paramount. Only transcriptional control prevents formation of unwanted intermediates.

Question 70

Know that transcriptional control includes two core mechanisms and what these are.

Answer 70

Control of transcription is effected by two mechanisms, the binding of sequence specific transcription factors to DNA and the control of DNA packing and chromatin structure.

Question 71

Briefly discuss features of eukaryotic transcription factors.

Answer 71

Transcription factors contain DNA binding and transactivation domains. Transcription factors act as dimers, and DNA contains both a major and minor grooves where sequence specific information can be read out by transcription factors. Transcription factors therefore contain protein features capable of ‘reading’ DNA sequences.

Question 72

Understand the concept of DNA looping and transcription factors acting at a distance from the promoter of a gene.

Answer 72

Most eukaryotic genes are controlled by comple cis-acting sequences within their promoters. There are often many cis-acting sequences, some are proximal to transcription start site, and some are far away from the start site.

Question 73

Describe the role of histones to higher order DNA structures.

Answer 73

The nucleosome is the lowest level of the higher order DNA structure in chromatin. There is a tight association of DNA with histone proteins.

Question 74

Describe the concepts of transcriptional co-activators and co-repressors and give general examples of such.

Answer 74

Transcription co-activators open the chromatin structure, such as histone acetyltransferases. Successive modification opens chromatin and promotes transcription.

Transcription corepressers close the chromatin structure, eg histone deacetylases.

Question 75

Give examples of transcription factors that control cell fate decisions and/or are implicated in human disease.

Answer 75

There are more than 4 Hox genes in humans, and all of them encode transcription factors which control brain and limb development. Each hox protein activates a battery of other genes and they affect how genes lead to congenital malformations.

Question 76

Explain what a mutation is.

Answer 76

A mutation is a change in a DNA sequence.

Question 77

Give examples of different types of mutagenic reagent.

Answer 77

DNA can be created by agents that are present in the cell or that are present in the environment. ie, UV light, ionizing radiation, chemical agents

Question 78

Discuss the possible consequences a mutation can have.

Answer 78

sometimes no consequence, transitions and transversions, frameshift, gross chromosomal changes that lead to genetic defects, cancer

Question 79

Explain why we do not suffer from many more mutations than we actually do despite our environment because of our efficient DNA repair systems.

Answer 79

base excision repair, nucleotide excision repair, and mismatch repair fixes DNA problems.

double stranded breaks can be fixed by homologous and non-homologous end joining

Question 80

Describe the process of excision DNA repair.

Answer 80

Glycosylases cleave the glycosidic bond of corresponding altered nucleotides. This leaves a deoxyribose residue with no attached base.

The deoxyribose residue is cleaved on one side (5’) by AP endonuclease, then the deoxyribose & adjacent nucleotides are removed by deoxyribose phosphate lyase. Gaps are then filled by DNA polymerase & ligase.