Case 2 Down's Syndrome Flashcards
What specialised proteins associate with DNA to form chromatin?
Histones
What are the 2 overall stages of mitosis?
Interphase
Mitotic phase
What occurs during interphase? (3 stages)
G1 - Cell growth, organelles copied, molecular building blocks created
S - Cell synthesis, complete copy of DNA in nucleus, centrosome duplicated
G2 - More cell growth, synthesis of proteins and organelles, re-organisation to prep for mitosis
What are the stages of mitosis?
Prophase Metaphase Anaphase Telophase Cytokinesis
What occurs during Prophase?
Chromosomes condense
Mitotic spindle forms
Nucleolus disappears
Prometaphase > chromosomes become very compact and are released from nuclear envelope
Microtubules bind to chromosomes at kinetochore
Where is the kinetochore found?
The centromere of each sister chromatid
What occurs during Metaphase?
Spindle captures chromosomes
Chromosomes up at metaphase plate
Kinetochores attached to microtubules from opposite spindle poles
What is the spindle checkpoint?
During metaphase, cell ensures all chromosomes are attached properly to kinetochores before proceeding to Anaphase
Cell will not move on if there is a problem at this stage until it is fixed
What occurs during Anaphase?
Sister chromatids separate from one another
Pulled to opposite sides of cell
Motor proteins drive cell elongation
What occurs during Telophase?
Mitotic spindle broken down
Two nuclei form
Nuclear membranes and nucleolus reappear
Chromosomes de-condense
What occurs during Cytokinesis?
Division of cytoplasm to form 2 new cells
What is cleavage furrow (cytokinesis)?
The pinch crease that separates the two cells
Carried out by the protein ACTIN
What is the difference between haploid and diploid cells?
Haploid (N) = half the number of chromosomes and are only in gametes
Diploid (2N) = full set of chromosomes (46 in humans)
How does Meiosis differ from Mitosis? (4 examples)
MEIOSIS IS:
4 daughter cells produced instead of 2
Haploid cells
Two step process
Germ cell division
What is Meiosis 1 sometimes called and why?
Reduction division - it halves the chromosome number from 92 to 46
What is synapsis?
In prophase 1: homologous chromosome pairs align opposite each other
What occurs during crossing over of chromosomes?
Each BIVALENT becomes tightly coiled, recombination occurs at points known as CHIASMATA where homologous regions of DNA are exchanged between chromatids
What is formed after Telophase 1 of Meiosis?
Two new daughter gametes HAPLOID chromosomes
What does Meiosis achieve and how?
Ensures HAPLOID number of chromosomes in daughter cells
Generates genetic diversity via random assortment and crossing over
What is the process of DNA replication
Replication starts at origin of replication
DNA Helicase unzips/unwinds
DNA Polymerase binds to exposed bases
On leading strand - replication is continuous
On lagging strand - replication occurs in Okazaki fragments
Okazaki fragments sealed by DNA Ligase
Sliding clamp holds DNA Polymerase in place
Topoisomerase prevents DNA ahead of fork getting too tightly wound
DNA Ligase replaces any nicks in sequence
What does it mean by DNA replication is semi-conservative?
Each strand in double helix acts as template for new, complementary strand
What does DNA Polymerase do?
Makes new DNA strand, requires a template and a primer, runs 5’ to 3’
What does DNA Ligase do?
Seals Okazaki fragments
What is a karyotype? When can it be taken?
A picture of an individual’s chromosomes
When cells are undergoing METAPHASE
What is polyploidy?
When cells have chromosomes in multiples of N higher than 2N (diploid)
e.g. 3N = 69 chromosomes = TRIPLOID
What is aneuploidy?
A variation in the number of chromosomes that is not in multiples of N
e.g. An extra copy of chromosome 21 (Trisomy 21) for Down’s Syndrome
What is monosomy?
A loss of a copy of that chromosome
What is trisomy?
An extra copy of a [articular chromosome
Are monosomies ever viable?
For monosomy of chromosomes 1 - 22, ALL complete monosomies are lethal
Partial monosomies may be observed in unbalanced translocations
Monosomy of the X chromosome results in Turner Syndrome (XO)
What can cause aneuploidy?
Non-disjunction - failure of chromosomes/sister chromatids to separate during anaphase
Anaphase lag - delayed movement of chromosomes after separation at anaphase
What is a balanced/unbalanced structural chromosomal abnormality?
Balanced: no loss of genetic material
Unbalanced: incorrect amount of chromosomal material
What structural abnormalities can be found in a single chromosome?
Deletion
Inversion
Duplication
Isochromosome
What structural abnormalities can be found across two chromosomes?
Insertions
Translocations
What are the two types of translocations?
Reciprocal - breakage of at least two chromosomes with exchange of fragments
Robertsonian - breakage of two acrocentric chromosomes at or close to their centromeres with subsequent fusion of their long arms (centric fusion)
Which chromosomes are involved in Robertsonian translocations?
13, 14, 15, 21, 22
What does colcichine do? When is it used?
Poisons mitotic spindle - used during metaphase to identify a karyotype
What is the FISH method?
Fluorescent In-Situ Hybridisation - uses fluorescent probes to bind to a complementary sequence in DNA, able to obtain a karyotype this way
What are the risks involved for a women aged >35 becoming pregnant?
Fewer viable oocytes Higher risk of gestational diabetes Higher risk of pre-eclampsia and eclampsia Higher risk of chromosomal abnormalities Higher risk of twins/triplets
What is the risk for mothers over aged 45 of having a baby with Down’s Syndrome?
1:33
What puts a parent more at risk for having a baby with Down’s Syndrome?
Being over aged 35
Having a previous baby with DS AND carrying the chromosomal translocation for it
What are the three different types of Down’s Syndrome?
Trisomy 21 - extra copy of chromosome 21
Translocation type - Robertsonian translocation (2 copies of chromosome 21 but some genetic material from 21 has translocated to another chromosome)
Mosaic type - Non-disjunction in meiosis but not all cells have trisomy 21 (VERY RARE)
What other health complications may occur in someone with Down’s Syndrome?
Congenital heart defects Learning disabilities Immune disorders Obesity Spinal problems Leukaemia Endocrine problems Seizures Dental problems Hearing and vision loss
What common congenital heart defects are observed in people with Down’s Syndrome?
Endocardial Cushion Defect (L>R shunting of blood through heart
Ventricular Septal Defect (failure to close intraventricular foramen)
Secundum Atrial Septal Defect (failure to close embryonic foramen)
What is a healthy BMI?
18.5 - 24.9
How does a high BMI affect fertility and pregnancy?
BMI > 30 can reduce fertility by up to 50%
Maternal diabetes
High blood pressure (pre-eclampsia)
