Genetics Flashcards
What are the phases of the cell cycle?
G1 phase
S phase
G2 phase
M phase
What is the M phase
Mitosis phase
What happens to cells in the G0 phase?
Stimulated by growth factor, resulting in activation of transcription factors that lead to the initiation of DNA synthesis, followed by mitosis and cell division.
What happens in G1 phase?
Chromosomes are prepared for replication.
What happens in synthetic phase?
46 chromosomes are duplicated into chromatids
What happens in interphase?
Replication of cellular genetic material and organelles to prepare for next division
What is the longest phase in the cell cycle?
Interphase
Which steps in the cell cycle constitute the interphase?
G0
G1
G2
S
Stages of mitosis?
Prophase
Metaphase
Anaphase
Telophase
What happens during prophase?
Condensation of chromatin
breakdown of nuclear envelope
spindles at opposite cellular poles
What happens during metaphase?
Alignment of chromosomes
What happens during anaphase?
Separation of paired chromosomes
What happens during telophase?
Chromosomes are packed into distinct new nuclei in emerging daughter cells.
Cytokinesis (division of cytoplasm) also starts
What happens in Meiosis 2?
Same as normal mitosis
What is a acrocentric/submetacentric chromosome?
Centromere is at one end, so arms are of unequal length.
What is telocentric?
When centromere is at tail end of chromosome.
What is a holocentric chromosome?
Entire length of chromosome acts as centromere.
When types of chromosomes are not seen in humans?
Telocentric
Holocentric
What is an aneuploid cell?
When a cell possesses chromosomal numbers different from normal diploid status.
What failure results in triploidy/tetraploidy?
Non-disjunction - failure of chromosome/chromatid to separate in meiosis
Rate of Downs?
1:700
Prominent findings in Downs?
Reduced maternal levels of alpha-fetoprotein
Increased beta-hCG
Increased nuchal fold thickness in fetal USS
What is 95% of Downs attributed to?
Meiotic nondisjunction of homologous chromosomes,
What are 4% of Downs due to?
Robertsonian Translocation
What characterizes Edwards syndrome?
Severe mental retardation Rocker bottom feet Low-set eats Micrognathia (small jaw) Congenital heart disease
Frequency of occurrence of Edwards syndrome?
1:8000
Which gender is Edwards syndrome more common in?
Three times more common in girls
Characteristics of Trisomy 13?
Severe mental retardation Microphthalmia Microcephaly Cleft lip/plate Coloboma eye Abnormal forebrain structures Polydactyly
Rate of occurrence of Patau’s?
1:6000
Cause of Turners in 80%?
Origin of aneuploidy is from paternal X chromosome, so Turners is of maternal origin
Occurrence of Turners?
1:2000 live-born female infants
IQ profile of Turners?
Lower than general population by mean of 10 points (nearly one SD) due to reduced performance IQ
Verbal IQ preserved
What are the purine nucleic acids in DNA?
Adenine
Guanine
Difference between DNA and RNA?
RNA is single stranded in humans
DNA is double stranded
What is an exon?
Polypeptide coding sequences in DNA
Types of sequences in introns?
Satellite
Mini-satellite
Micro-satellite
When are introns removed?
ntrons are removed from mRNA before it leaves the nucleus and starts protein synthesis.
What is the name of synthesis of RNA from nuclear DNA?
Transcription
In cell nucleus
What is heterogeneous nuclear RNA?
Transcripted RNA which contains junk sequences (introns) that do not code for polypeptides,
Where are transfer RNAs synthesized
Synthesized from DNA in nucleus
What happens in termination?
Chain termination is signaled by one of three codons; UAA, UGA, UAG
What is modification?
Post-translational changes in a protein molecule before it becomes functionally active.
Where do modifications take place?
Endoplasmic reticulum
Golgi bodies
Where does protein destruction occur?
Lysosome
What is transcriptomic?
Study of mRNA using microchip arrays
Define a mutation
Sudden, permanent and heritable change in DNA sequence
What is a point mutation?
Single-base alteration in DNA
What can lead to point mutations?
Substitution - one base replaced by another
Transition - if purine is replaced by another purine/pyrimidine with pyrimidine
Trans version - purine replaced by pyrimidine and vice versa
What happens in frame mutation?
Changes in multiples of 3 bases, therefore no disturbance in actual reading frame
Types of effects of mutations on protein product
Silent
Mis-sense
Nonsense
What is a silent mutation?
No change in protein product
What is a mis-sense mutation
New mutant codon specifies a different aa with variable effects in final protein.
What happens in non-sense mutation?
New codon is either: UUA UGA UAG which signal stop to aa sequence, therefore nonfunctional protein
What are most translocations described as?
Reciprocal - one segment is exchanged for another segment among chromosomes
What is the Robertsonian translocation?
Non-reciprocal (unequal exchange) resulting in single fused chromosome from 2 acrocentric chromosomes.
Type of transmission of DiGeorge?
Autosomal dominant
Risk of schizophrenia if offspring has deletion for DiGeorge?
25%
Features of DiGeorge?
Mild-moderate LD Facial deformities (cleft palate) Absent/malformed parathyroids leading to hypocalcaemia Broad nasal bridge Articulatory speech and swallow problems
Location of transmission in Williams syndrome?
7q11 micro deletion
Features of Williams syndrome?
Hypercalcemia at birth Supra valvular aortic stenosis Moderate LD Disinhibited disposition Speech appears superficially fluent Hyperacusis
Features of Angelman syndrome?
Low IQ
Jerky movements - especially hand flapping
Frequent smiling
Seizures
Features of Prader-Willi?
Obesity Short stature Small limbs Decreased IQ Hyperphagia and skin pricking
First law of Mendelian inheritance?
Law of uniformity;
if two organisms that differ in one trait are crossed, resulting hybrid will be uniform in that trait
What is the second law of Mendelian inheritance?
Principle of segregation;
for any particular trait, the pair of alleles of each parent separate and only one allele passes from each parent to the offspring, based on chance
What is the third law of Mendelian inheritance?
Principle of independent assortment;
How does X inactivation occur?
DNA methylation
What is unfavorable Lyonisation?
When during random X inactivation, most X chromosomes carrying normal alleles are inactivated
What type of inheritance is Tuberous sclerosis?
AD
1 in 30000
Features of Tuberous sclerosis
Adenona sebaceum Normal to severe MR (heart) Ash leaf macules Brain hamartomas Heart and kidney cysts
Features of Apert syndrome?
Variable MR Cranio synostosis Shallow orbits Trapezoid mouth Mitten hands and feet AD
Inheritance of Noonan syndrome?
AD
Chromosome 12
Risk of Noonan syndrome?
1 in 1500
Features of Noonan syndrome
Mild MR Short stature Nuchal oedema/webbed neck Pulmonary stenosis Cryptorchidism
Type of inheritance of Lesch-Nyhan syndrome
X linked recessive
Features of Lesch-Nyhan syndrome
Poor muscle control
Moderate mental retardation - year 1
Self-mutilating behaviour - lip and finger biting
Hyperuricaemia and Hyperuricosuria (gout and kidney problems)
Give e.g. of X-linked inheritance
Haemophilia A/B
Duchenne Muscular Dystrophy
Androgen insensitivity syndrome
Commonest cause of blindness in young men?
Commonest cause of blindness in young men?
Examples of Trinucleotide repeat disorders
Fragile X
Friedreich Ataxia
Huntingtons
Myotonic dystrophy
Where is the mutation in Fragile X?
CGG
Where is the mutation in Friedreich?
GAA
Where is the mutation in myotonic dystrophy?
CTG
Which two conditions result in most cases of mental retardation in males?
Downs
Fragile X
Which gene results in Fragile X?
Expansion of CGG proximal to FMR1 gene
Features of Fragile X (male)
Enlarged testes Prominent ear lobes Protracting jaw High pitched voice Mental retardation
What are premutant carriers of Fragile X at risk of?
Developing intention tremor and ataxia after middle taxia
What are premutation carriers in Fragile X?
Those who carry increased number of CGG repeats in FMR1 locus but do not have clinical phenotype
What are women who are premutation carriers for Fragile X at risk of?
Premature ovarian failure
Mild cognitive/behavioral abnormalities
Prevalence of Huntington’s?
5 per 100000
What is the gene that causes Huntington’s?
Expanded and unstable CAG trinucleotide repeat on short arm of chromosome 4-4p16.3
What is genomic imprinting?
Where the disease phenotype expressed depends on whether allele is maternally or paternally inherited.
What is polymorphism?
Variations in genetic make-up at a particular locus noted in the healthy population - at least in 1% of population
What are single nucleotide polymorphisms?
If polymorphism is to due to change in single nucleotide in a sequence.
How can single based polymorphisms be assayed?
DNA sequencing
DNA chips
What are variable number of tandem repeats?
Polymorphism due to varying number of repeats in specific region of chromosome.
How are variable number of tandem repeats classified?
Short tandem repeat polymorphism
Microsatellite (2-6 bases)
Minisatellite (20-bases)
Where do most polymorphisms occur in a gene?
Introns
Features of those with short allele of 5HTTLPR?
Low expression of serotonin transporter
What is short variant of 5HTTLPR speculated to be linked to?
Higher incidence of affective disorders, neuroticism, anxiety and PTSD
When is southern blotting used?
For detecting specific sequence of DNA
When is western blotting used?
Detection of specific protein after electrophoresis
When is northern blotting used?
Detection method for specific RNA after electrophoresis.
What does PCR do?
Amplifies minute amounts of DNA, allowing further analysis
What does the Hardy Weinberg equilibrium determine?
The frequency of an abnormal gene or genotype in the population.
What is epistasis?
Gene-gene interaction, particularly between different alleles
What is locus heterogeneity?
When same disease phenotype can be caused by mutations in different loci.
What is allelic heterogeneity?
Same disease phenotype resulting form different types of mutations at same loci.
What is pleiotropy
When single disease-causing mutation affects multiple organ systems.
