Numerical Chromosomal Abnormalities Flashcards
1
Q
Describe the major phases of the cell cycle
A
- G1: Cellular contents, excluding the chromosomes are duplicated
- S phase: Each of the 46 chromosomes is duplicated by the cell
- G2: The cell double checks the duplicated chromosomes for error, making any needed repairs
- Mitosis: Forms 2 daughter cells
- Cytokinesis
2
Q
Describe what occurs in the S-phase and the type of chromsome formed?
A
- DNA (single chromatid) is replicated to form sister chromatids
- These are paired together in homologous chromosomes
- Homologous chromosomes refer to a pair of chromosomes having the same gene sequences, each derived from one parent (maternal and paternal)
- In a pair of homologous chromosomes, one is inherited from the male parent, and the other from the female parent
3
Q
Describe the genetic locus location and function in a gene
A
- A genetic locus is the location of a particular gene on a chromosome
- At each genetic locus, an individual has two alleles, one on each homologous chromosome
4
Q
What is mitosis?
A
- Mitosis = Division of all cells apart from the production of gametes
- PMAT: Prophase, Metaphase, Anaphase, Telophase
- 1 diploid = 46 chromosomes (2n) becomes 2 diploid = 46 chromosomes (2n)
5
Q
Describe the key stages involved (PART 1)
A
- Interphase: Chromosomes duplicate and the copies remain attached to each other
- Prophase: In the nucleus, chromosomes condense and become visible. In the cytoplasm, splindles form
- Prometaphase: The nuclear membrane breaks apart and the spindle starts to interact with the chromosomes
- Metaphase: The copied chromosomes align in the middle
6
Q
Describe the key stages involved (PART 2)
A
- Anaphase: Chromosomes separate into 2 genetically identical groups and move to opposite ends of the spindle
- Telophase: Nuclear membranes form around each of the 2 sets of chromosomes, the chromosomes begin to spread out, and the spindle begins to break down
- Cytokinesis: The cell splits into 2 daughter cells, each with the same number of chromosomes as the parent. In humans, such cells have 2 copies of 23 chromosomes (diploid)
7
Q
Give some key features of mitosis (5)
A
- Sister chromatids are identical
- Each daughter cells recieves 1 chromatid of each chromosome and are genetically identical to parent
- Homologues do not interact
- Align as 46 separate chromosomes - each behaves independently
- All somatic cells (from body)
8
Q
What is meiosis?
A
- Meiosis = Division of cells for production of gametes (sperm/egg)
- Leads to genetic variation
- 2 cell divisions of 1 diploid (46 chromosomes) into 4 haploid (23) daughter cells.
9
Q
Describe meiosis I
A
- Align as 23 bivalents (pairs of HCs)
- Allows for chiasma formation (i.e. recombination)
- Pulls apart homologues from one another
- Daughter cells have 23 chromosomes (each with 2 chromatids)
10
Q
Describe meiosis II
A
- Align as independent chromosomes
- Sister chromatids pulled apart
- Daughter cells have 23 chromosomes (each of 1 chromatid)
11
Q
What occurs when homologous chromosomes align?
A
- HC align which form a bivalent structure (pair of HCs) held together by the synaptonemal complex
- Once aligned, they undergo crossing over
- Crossing over = Exchange of genetic material via reciprocal breaking + re-joining between homologous chromosomes
- Forms a chiasma as the point of contact between the 2 non-sister chromatids of HCs
12
Q
What is the purpose of this?
A
- Crossing over forms recombinant chromsomes (Opposite strand is of other non-sister chromatids) and non-recombinant chromosomes (same strands as before)
- Crossing over will then result in recombination - production of different combinations of alleles in offspring
- Ultimately results in exchange of chromosomal segments and new allele combinations
13
Q
Describe independent assortment?
A
- Describes How pairs of alleles (maternal + paternal) separate independently from one another during meiosis
- Occurs randomly - equal chance of pairing or separating with any other chromosome
14
Q
State the 2 mechanisms involved that introduces natural variation in meiosis and what does it result for the daughter cell?
A
- Natural variation arises by:
- Independent assortment of chromosomes
- Recombination (via crossing over)
- Means daughter cells are genetically unique
15
Q
Describe the normal human karyotype
A
- Karyotype = Number + visual apperance of chromosomes in an organism
- Humans have 23 pairs of chromosomes
- 22 pairs autosomes and 1 pair sex chromosomes (XX or XY)
16
Q
State the 3 types of chromosomes found and what chromosomes they are found in?
A
- Based on the location of the centromere
- Metacentric: p & q arms even length, 1-3, 16-18
- Submetacentric: p arm shorter than q, 4-12, 19-20, X
- Acrocentric: Long q, small p, p contains no unique DNA, 13-15, 21-22, Y
17
Q
State what haploid and diploid mean?
A
- HAPLOID: One set of chromosomes (n=23) as in a normal gamete.
DIPLOID: Cell contains two sets of chromosomes (2n=46; normal in human)
18
Q
State what polyploid and aneuploid mean?
A
- POLYPLOID: Multiple of the haploid number (e.g. 4n=92)
- ANEUPLOID (non-disjunction): Chromosome number which is not an exact multiple of haploid number - due to extra or missing chromosome(s) (e.g. 2n+1=47)
19
Q
Difference between trisomy and monosomy aneuploid?
A
- Trisomy = extra chromosome
- Monsomy = missing chromosome
20
Q
What leads to chromosomal abnormalities?
A
- Meiosis leads to genetic variation
- If the process goes wrong through meiotic non-disjunction, it can lead to disease - chromosomal abnormalities
21
Q
What is meiotic non-disjunction and how does it arise?
A
- Meiotic non-disjunction is the failure of homologous chromosomes (MI) or sister chromatids (MII)
- To segregate properly at opposite poles during meiosis, results in the production of gametes that have an improper chromosome complement.
- When a normal gamete combines with a gamete that has an extra chromosome, the resulting zygote is trisomic
- Occurs at either Meiosis I or Meiosis II
22
Q
State 3 examples of autosomal aneuploidies?
A
- Trisomy 13 (Patau’s, 2 in 10,000 births)
- Trisomy 18 (Edward’s, 3 in 10,000)
- Trisomy 21 (Down’s, 15 in 10,000)
- Others happen but do not carry to term (won’t survive)
23
Q
State 3 examples of sex chromosome aneuploidies?
A
- Turner’s (45,X) (1 in 5000 female births)
- Triple X syndrome (47,XXX) (1 in 1000 female births)
- Klinefelter’s (47,XXY) (1 in 1000 male births)
24
Q
What is mitotic non-disjunction?
A
- Failure of sister chromatids to segregate properly to opposite poles during mitosis
- Only a portion of cells will be affected - Meiotic ND occurs in zygote so every cell will be affected (carrying extra or missing chromosome)
- Majority of cells will be 2n, some 2n+1 (mosaic/trisomic) and 2n-1 (monosomic- these will die out)
25
Q
What is mosacism?
A
- The presence of two or more genetically different cell lines (cells with different number of chromosomes) derived from a single zygote
- As a result of mitotic ND
26
Q
What mechanism occurs in maternal non-disjunction?
A
- Zygote (trisomic) cell will recognise that there are wrong number of chromosomes and throw out one of the copies (randomly) to bring back cell to disomic
- Occurs via trisomy rescue anaphase lag - scenarios:
- normal biparental contribution (each from one parent)
- If both of the retained chromosomes come from the same parent, then uniparental disomy results
27
Q
How does this result in mosacism?
A
- This will result in mosacisim as it goes from 100% of cells being trisomic to a portion of the cells
- Below shows possible scenarios
- VD
28
Q
What is the clinical relevance of having a mosaic phenotype compared to a complete trisomic phenotype?
A
- Mosaic phenotype thought to be less severe
- Difficult to assess as only proportion of cells are affected: Dependent on
- What are the proportions of different cell types?
- Which tissue/organs are affected?
29
Q
How can partial trisomy/monosomy arise?
A
- Full monosomy arises by non disjunction
- Partial monosomy/trisomy (microdeletion/duplication syndromes) far more common
- Mechanism different
- Partial in the sense it is lacking parts of gained additional parts of the chromosome
