WEEK 9 Flashcards
Describe the structure of a chromosome.
Centromere in middle
Has a long arm (q) and a short arm (p)
The tips of it = telomeres. These give the chromosome stability
How is a chromosome recognised? (HINT: there’s 3 ways)
- Banding pattern with specific stains
- Length
- Position of centromere
What is an acrocentric chromosome? What chromosome numbers does this happen to?
The short arm is almost non existent and so therefore it doesn’t really matter
- Chromosomes 13, 14, 15, 21, 22.
What are the various chromosome changes which cause disease? (HINT: there’s 2)
- Balanced chromosomal rearrangement
- all the chromosomal material is present - Unbalanced chromosome rearrangement
- extra/missing chromosomal material
- usually 1 or 3 copies of some of the genome
Explain what abnormality has occurred in (i) Down Syndrome (ii) Edwards Syndrome (iii) Patau syndrome (iv) Turner Syndrome.
(i) trisomy of chromosome 21
(ii) trisomy of chromosome 18
(iii) trisomy of chromosome 13
(iv) females that lack an X chromsome (45X)
What disease results from a chromosome complement of (i) 47XXX (ii) 47XXY ?
(i) triple X (trisomy X)
(ii) Klinefelter Syndrome
What is a robertsonian translocation?
When 2 acrocentric chromosomes are stuck end to end
- normally the individual wouldn’t show any phenotype of this
However, if someone with this chromosomal pattern has children, then there’s an increased risk of trisomy:
have a 1 in 4 chance of normal, balanced translocation, trisomy 14 (miscarriage), trisomy 21 (down syndrome)
What is a reciprocal translocation?
When fragments of the chromosomes are translocated, can either result in dicentric and acentric translocation (which is not stable in mitosis), or the exchange of 2 acentric fragments which is stable
When a parent with a reciprocal translocation, there offspring have a 1 in 4 chance of:
normal
balanced 1;9 translocation
partial trisomy 9 & monosomy 1
partial trisomy 1 & monosomy 9
E.g. MUM = 46, XX, t(12;17)(p13;p13)
SON = 46, XY, der(17)t(12;17)(p13;p13)
What are the reproductive risks of reciprocal translocations?
For most translocations, approx. 50% will have either normal chromosomes or the balanced translocation
Unbalanced products result in:
- Miscarriage (if large segments translocated)
- Dysmorphic delayed child (if small segments)
What is the Philadelphia chromosome?
Occurs in leukaemia (very common in CML)
Some of chromosome 9 is translocated onto chromosome 22
=> giving it increased activity compared to normal (this is what drives cancer)
E.g. 46, XY, t(9;22)(q34;q11.2)
What are the types of single chromosome mutations? Give examples of diseases/syndromes that arise as a result of said mutations.
- DELETION
- X linked ichthyosis - DUPLICATION
- Charcot marie tooth disease = damage to the myelin sheath in peripheral nerves => progressive loss of muscle tissue & touch sensation (pain remains intact) - INVERSION
- inv(9)(p11;q12) = commonest
What is quantitative inheritance?
When both genetic and environmental factors contribute to determining the risk of disease.
Why are complex traits probabilistic?
Because even if you have all the susceptible alleles, the disease still depends on whether you encounter certain environmental hazards
What is the difference between a mutation and a polymorphism?
A mutation is when a gene change directly causes a genetic disorder
A polymorphism is any variation in the human genome that has a population frequency of greater than 1% OR any variation in the genome that doesn’t cause disease in its own right, but it may predispose to disease
What are the 2 ways to measure the genetic contribution to a disease? Describe both.
- FAMILY STUDIES
- this method doesn’t take into account a risk caused by a shared environment
E.g. males are more prone to disease (=> have a lower liability threshold), if a female is affected, she must be at the high end of the curve (i.e. need more “contributing” genes) - TWIN STUDIES
- monozygotic share all genes, dizygotic share about 50%
=> for a disease w. genetic contribution, you would expect a monozygotic twin to be affected more frequently than a dizygotic twin
BUT this doesn’t take into account that being a monozygotic twin itself predisposes to disease
What is used to find out whether a polymorphism contributes to a disease? What are the potential problems with these studies? How are these problems overcome?
ASSOCIATION STUDY METHOD
- look at affected and non affected and work out who has polymorphism and who doesn’t in each group
POTENTIAL PROBLEMS:
- how do u know which gene to look at as the disease could be influenced by 1 or 1000 genes
- how do you know which polymorphism to look at as there’s 10-12 mil in the human genome
- when you’re using many polymorphisms, some will give a significant result by chance, so which are true?
- Your control group has to match affected group
OVERCOME:
- Testing the whole genome and then working out what ones are significant
What are some of the characteristic of multifactorial diseases?
- they exclude single gene/syndromic forms (rare)
- there’s a higher recurrence risk if:
(i) more affected family members
(ii) more severely affected family members - risk or recurrence data is calculated empirically (gene tests rarely help unless there’s a monogenic form of disease)
What is the definition of (i) Differentiation (ii) Fate (iii) Potency?
(i) process by which embryonic cells become different from one another, involving the emergence of cell types such as muscle, nerve, skin and fat cells
(ii) describes what a cell will become in the normal course of development
(iii) the entire repertoire of cell types a particular cell can give rise to in all possible environments
What are the 2 stages of commitment? Describe them.
(1) SPECIFICATION (reversible)
- capable of differentiating autonomously if placed in isolation BUT can be respecified if exposed to certain chemicals/signals
(2) DETERMINATION (non-reversible)
- cells will differentiate autonomously, even when exposed to other factors or placed in a different part of the embryo
How does a naive cell become specified?
INTRINSIC SIGNAL (cytoplasmic determinant) - autonomous signal tells cell "WHO it is" EXTRINSIC SIGNAL (induction) - chemical/molecule in environment that gives cell spatial info, tells cell "WHERE it is"
What is competence?
The ability of a cell to respond to the chemical stimuli
- A cell can lose competence by changes in the surface receptor or intracellular molecules
How can gene activity be reversed experimentally?
By somatic cell reprogramming, if:
- Therapeutic cloning: creating ES cells through Somatic Cell Nuclear Transfer
- By defined Factors: creating IPS (induced pluripotent stem) cells
What does differentiation establish?
A tissue specific pattern of gene activity, which is passed onto daughter cells
What is the patterning of bone and tissue regulated by?
HOX genes
- HoxA and HoxD are very important for limb development
What are the 2 types of stress?
DISTRESS
- harmful and damaging
EUSTRESS
- beneficial and constructive
Describe one assessment of major and minor life events.
MAJOR = Social Readjustment Rating Scale (SRRS)
- based on the adjustment required for certain life events
- list of life events rated on a scale of 0-100.
- adult indicates what events have happened to them within the past 12 months and the values are added to give a total score
MINOR = Hassels scale
e.g. HASS/Col
- day to day unpleasant OR potentially harmful events
What are the main sources of life event stressors?
- INDIVIDUAL
- illness, conflict, personal relationship, lacking control - FAMILY
- divorce, marriage, illness, disability, death, addition to family - SOCIETY
- job, environment
What are the stages that a cell undergoes to induce cancer?
Normal - Dysplasia - Carcinoma in situ - Invasion - Metastasis
