GEP (Life Cycle) Week 4 Flashcards
Define these basic Genetic terminology:** Gene, Locus, Chromosome, Chromatid, Genotype, Phenotype, Allele**
- Gene - a DNA segment with nucleotide sequence encoding RNA
- Locus - a location of a gene or DNA sequence on a chromosome
- Chromosome - a structure found in the nucleus of eukaryotes that contain genes
- Chromatid - 2 identical strands of replicated chromosomes
- Genotype - chemical composition of DNA
- Phenotype - observable traits of an organism
- Allele - a variant of a particular gene
How many pair of chromosomes do we have
- We each have 23 pairs of chromosomes
22 autosomes, 1 sex - Each chromosome is made up of 2 sister chromatid which are joined by a centromere
- P arm = short arm, no coded genes
- Q arm = longer arm
- Telomere = chromosome cap
-Non coding DNA
-Shortens every replication cycle
Give a brief overview on DNA and Nucleotide, providing what they are and how they work
DNA – deoxyribose nucleic acid
Double helix
Read 5’-3’
Read in triplets (codons)
Sugar phosphate backbone joined by hydrogen bonds
Negatively charged molecule
Nucleotide – base molecule
Adenine (A) binds Thymine (T)
Cytosine (C) binds Guanine (G)
Adenine (A) binds Uracil (U) in RNA
What are Histones
**Histones – group of proteins that bind to DNA and support structure of chromatin **
* Positively charged
* Four core histones forming an octet
* Imagine beads on a string
* Allow efficient super coiling
What are chromatins
Chromatin – DNA and associated proteins forming a nucleosome
* Euchromatin – loosely packed – genes can be transcribed
* Heterochromatin – tightly packed – genes are silence
A nucleosome is the basic structural unit of DNA packaging in eukaryotes. The structure of a nucleosome consists of a segment of DNA wound around eight histone proteins and resembles thread wrapped around a spool. The nucleosome is the fundamental subunit of chromatin.
Give a brief overview of Interphase Cell cycle
Interphase
* G1
Synthesis of RNA, proteins and organelles
One chromatid per chromosome
Lasts hours-months
* S
DNA replication → 2 sister chromatids per chromosome
Site of most mismatch repair
Once S phase is initiated, cell cycle must take place
Approx 8 hours
* G2
More protein synthesis required for mitosis
Repair of DNA replication errors
Give a brief overview of Mitosis phase in cell cycle
Now give an overview of Mieosis
Split into 2 key phases
Meiosis I → very similar to mitosis
Meiosis II → further division to form haploid cells
Creation of genomic diversity
Independent assortment = random orientation of homologous chromosome pairs in Metaphase I
Crossing over in Prophase I
Independent assortment to form haploid cells in Metaphase II
How do we visualise chromosomes
Karyotyping / G banding - This is done with a giemsa stain and can be used to determine number of chromosomes, their morphology, banding pattern and length ratio of each chromosomal arm. It can be done with samples from tissues like the amniotic fluid, placenta, or bone marrow and is most helpful for diagnosing trisomy, monosomies and sex chromsomes disorders.
FISH - used to stain for SPECIFIC DNA SEQUENCEs using fluoresecent labelled DNA or RNA probes. It’s not limited to checking for specific chromosomal abnormalities but can also be used to check for known mutations in certain cancers
DNA microarrays - detect copy number alterations across the genome. There are two different ways of performing microarray testing: array comparative genomic hybridisation (aCGH) and single nucleotide polymorphism array (SNP array).
aCGH specific limitations: cannot detect triploidy, uniparental disomy or copy-number neutral loss of heterozygosity. SNP array specific limitations: coverage is limited to regions where there is SNP variation between individuals.
What is the term used for chromosome abnormality
Aneuploidy
What are the most common forms of aneuploidy
Trisomy 13 - Patau Syndrome
Trisomy 18 - Edward Syndrome
Trisomy 21 - Down’s Syndrome
47XXY - Klinefelter
45 XO - Turner Syndrome
47 XXX - Triple X syndrome
A trisomy is a chromosomal condition characterised by an additional chromosome. A person with a trisomy has 47 chromosomes instead of 46.
How do aneuploidy happen
Aneuploidy occurs during meiosis when pairs of chromosomes don’t complete the process of cell division and fail to separate. Aneuploidy is random and unpredictable
Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate properly during cell division.
Give an overview on what klinefelter syndrome
Give an overview on Turner’s syndrome
What is Trisomy 13 and give an overview of the condition
-1 in 100,000 births
-Nondisjunction / Robertsonian translocation
-Poor prognosis, only 5% survive past 6 months
**Clinical features **
Midline defects
Post axial polydactyly
Congenital heart defects
Renal abnormalities
Nondisjunction is the failure of homologous chromosomes or sister chromatids to separate properly during cell division.
Robertsonian translocations are a specific class of translocations in which two acrocentric chromosomes fuse at their centric ends (45). In humans, chromosomes 13, 14, 15, 21, and 22 are acrocentric, and all of these chromosomes are associated with Robertsonian translocations.
What is Trisomy 18 and give an overview of the condition
-1 in every 6000 births
-30% die within 1 month, 50% in 2 months and 90% within a year
RFs:
Older maternal age
FHx
Female birth (3x)
Clinical features
Fixed flexion
Short sternum
Renal abnormalities
Congenital heart defects
Inguinal and diaphragmatic hernias
What is Trisomy 21 and give an overview of the condition
1 in 650-1000 live births
Nondisjunction (95%), Robertsonian (4%) and Mosaicism (1%)
Biggest risk factor is maternal age
Screening programme for trisomy 21 is in place
Mosaicism occurs when a person has two or more genetically different sets of cells in his or her body
Development milestones
Define these key embryology terminologies: **Morula,
- Morula – 16 cells Surrounded by zona pellucida.
Define these key embryology terminologies: **Blastocyst,
32 cells
Compaction of morula
Fluid enters to form a cavity (blastocoele)
Zona pellucida will dissolve, allowing implantation.
Give an overview of what gastrulation is
- The differentiation of the bilaminar disc to 3 germ layers
- 15 days post fertilization
- Consists of ectoderm (outer), mesoderm (middle) and endoderm (inner)
- Epiblasts will migrate through the primitive streak between epiblast and hypoblast layers and form intraembryonic mesoderm.
- Hypoblast is replaced by epiblast forming the endoderm.
- Original endoderm becomes ectoderm.
Cranial end of hypoblast is the prochordal plate containing columnar cells.
Cells migrate down from the epiblast and differentiate, this forms a macroscopically visible primitive streak
At the cranial end, cells migrate quickly forming the primitive node.
Gradually the primitive streak will elongate.
Cells the differentiate into endoderm will replace the hypoblast layer. They are able to detach and slip into the interior of the embryo displacing the hypoblast completely and replacing it with the definitive endoderm.
Cells which stay in the epiblast layer will differentiate into ectoderm.
Some cells will force their way between the ectoderm and endoderm to form the mesoderm.
Around day 16
Give an overview of what the germ level derivatives are
Give an overview on Neurulation
- This begins with the development of the notocord.
- Notochord will migrate along the primitive streak and ends at the prechordal plate.
- It is made of epiblast cells that migrate from the primitive node and extend to the cranial aspect of the disc.
Neurulation:
Formation of the neural tube and neural crests after gastrulation
Notochord will secrete signaling molecules -> triggers the differentiation of ectoderm cells to form neural cells
This will form the neural plate.
The neural plate will invaginate and become the neural groove.
Folds are found on either side and will converge
The neural groove will convert to a cylindrical neural tube.
The most dorsal part forms the neural crest
The neural crest will form peripheral nervous system neurons
There are a cranial and caudal neuropores which should close.
Neural tube forms and closes in week 4
Give an overview on somitogenesis
Somites = mesoderm mass formed from presomitic mesoderm after gastrulation.
* They are laid down sequentially from cranial to caudal end.
* Controlled by developmental clock/wavefront - gene expression cycles.
* Epithelial somites differentiate to:
Sclerotome - verterbrae and ribs, heart tissue
Myotome - muscle tissue, limb muscles, epimere and hypomere
Dermatome - dorsal dermis
Syndetome - tendons
* This is a continuous process - akin to sausage making.
Rapidly dividing cells being periodically segmented by opposing signalling mechanisms.
Somites are blocks ofmesodermthat are located on either side of theneural tubein the developing vertebrate embryo. Somites are precursor populations of cells that give rise to important structures associated with the vertebrate body plan and will eventually differentiate into dermis, skeletal muscle, cartilage, tendons, and vertebrae. Somites also determine the migratory paths ofneural crest cellsand of the axons of spinal nerves.
