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
What are the clinical features of Trisomy 21
General: Hypotonia, Below average weight and height
Face and Head: Small nose, flat nasal bridge, small mouth tongue may stick out, Epicanthic folds, small head with flat back- brachcephaly
Hands and Feet: Broad hands, short fingers, singular palmar crease, incurved 5th finger, gap between first and second toe.
Hypotonia: reduced muscle tone
Epicanthic foldsare folds of skin covering the medial portion of the eye and eyelid.
What are the complications of Trisomy 21
- Learning disabilities
- Heart defects: most commonly ventricular septal defects
- GIT: coeliac, Hirschsprung’s disease
- Hearing and visual impairments: recurrent OM, glaucoma
- Increased suseption to infections
- Dementia: same gene as Alzheimer’s (amyloids)
- Thyroid: hypothyroidism
- Leukemia: AML / ALL
- MSK: scoliosis
Hirschsprung’s disease: absence of parasympathetic ganglion cells of myenteric plexus, responsible for peristalsis of the bowel.
What are the prognosis of Trisomy 21
Prognosis: has dramatically improved and life expectancy increased in recent decades due to improved surgical repair of congenital heart defects. Leading causes of death in adults with Down’s syndrome are respiratory infections and cardiac causes. Dementia is also a big contributor to deaths. Average life expectancy now 60 years.
What are Antenatal screening for down syndrome
Combined Test which includes:
1. Nuchal translucency ultrasound (11-14 weeks) -> great than 6mm
Fluid filled subcutaneous space at back of foetal neck, thickening is associated with trisomies and Turner’s
- Maternal blood tests (10-14 weeks)
PAPP-A = pregnancy-associated plasma protein A
Beta hCG
AFP = alpha-fetoprotein
Quadruple test (14-20 weeks)
No ultrasound
1. Beta hCG
2. AFP
Serum oestriol
Inhibin-A
**High risk blood results for Down’s Syndrome:
Decreased PAPP-A, AFP, serum oestriol
Increased beta hCG and inhibin A **
AFP = Protein synthesised by yolk sac and foetal liver (foetal homologue of albumin). ↓ in pregnancy associated with: Down Syndrome, Turner Syndrome, trisomy 13, trisomy 18, Cornelia de-Lange syndrome.
PAPP-A = protein produced by placenta.
↓ PAPP-A levels in 1st trim associated w. aneuploidy, miscarriage, hypertension, intrauterine growth restriction, gestational DM.
Trisomy 21 diagnosis = karyotyping via amniocentesis or CVS (chorionic villus sampling)
What are the 4 main areas of development
4 main areas:
Gross motor
Vision and fine motor
Hearing and communication
Social, emotional and behavioural
→ Biological, psychological, physical and emotional; changes occurring in humans as they progress from dependence to autonomy, usually for clinical application the first 5 years of childhood
Development milestones
What are the different classification of diagnosing delayed development.
Global Development Delay:
Significant delay in at least 2 developmental domains of gross/fine motor, speech/language, cognition, social/personal, activities of daily living, affecting children under 5 years of age
Usually present in first 2 years of life
Specific developmental delay
Delay affecting one or two developmental domains only